Consumption of Dietary Resistant Starch Partially ... - ACS Publications

Subscriber access provided by Heriot-Watt | University Library

Article

Consumption of Dietary Resistant Starch Partially Corrected the Growth Pattern despite Hyperglycemia and Compromised Kidney Function in Streptozotocin-induced Diabetic Rats Gar Yee Koh, Matthew J. Rowling, Kevin Schalinske, Kelly Grapentine, and Yi Ting Loo J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.6b03808 • Publication Date (Web): 23 Sep 2016 Downloaded from http://pubs.acs.org on September 27, 2016

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers

Journal of Agricultural and Food Chemistry is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Subscriber access provided by Heriot-Watt | University Library

and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Journal of Agricultural and Food Chemistry is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 29

Journal of Agricultural and Food Chemistry

TYPE 1 DIABETES

ACS Paragon Plus Environment


1

Consumption of Dietary Resistant Starch Partially Corrected the Growth Pattern

2

despite Hyperglycemia and Compromised Kidney Function in Streptozotocin-

3

induced Diabetic Rats

4 5

Gar Yee Koh*, †, §, ¥, Matthew J. Rowling†, §, Kevin L. Schalinske†, §, Kelly Grapentine§, Yi

6

Ting Loo§

7 8

†

9

University, Ames, Iowa, United States.

The Interdepartmental Graduate Program in Nutritional Sciences, Iowa State

10

§

11

50011, United States.

12

¥

13

Tufts University, Boston, Massachusetts 02111, United States.

Department of Food Science and Human Nutrition, Iowa State University, Ames, Iowa

Present address: Jean Mayer USDA Human Nutrition Research Center on Aging at

14 15

*Corresponding author:

16

Gar Yee Koh, Ph.D.

17

Vitamins and Carcinogenesis Laboratory,

18

Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University,

19

711 Washington Street, Boston, Massachusetts 02111, United States.

20

Tel: +1 617 556 3222

21

E-mail: [email protected]

1 ACS Paragon Plus Environment

Page 2 of 29

Page 3 of 29


22

ABSTRACT

23

We previously demonstrated that feeding of dietary resistant starch (RS) prior to the

24

induction of diabetes delayed the progression of diabetic nephropathy and maintained

25

vitamin D balance in streptozotocin (STZ)-induced type 1 diabetic (T1D) rats. Here, we

26

examined the impact of RS on kidney function and vitamin D homeostasis following STZ

27

injection. Male Sprague-Dawley rats were administered STZ and fed a standard diet

28

containing cornstarch, 20% RS, 10% RS, or 5% RS for 4 wk. T1D rats fed the 10% RS

29

and 20% RS, but not 5% RS, gained more weight than cornstarch-fed rats. Yet, renal

30

health and glucose metabolism was not improved by RS. Our data suggest that RS

31

normalized growth patterns in T1D rats after diabetes induction in a dose-dependent

32

manner despite having no effect on blood glucose and vitamin D balances. Future

33

interventions should focus on the preventative strategies with RS in T1D.

34

35

KEYWORDS: 25-hydroxycholecalciferol; diabetic nephropathy; high-amylose maize;

36

Streptozotocin; type 1 diabetes; resistant starch; vitamin D

37

38



39

INTRODUCTION

40

Diabetes is an epidemic that affects approximately 23 million Americans 1. If left

41

uncontrolled, diabetes typically leads to severe macrovascular and microvascular

42

complications such as atherosclerosis, diabetic retinopathy, and diabetic neuropathy. It

43

is the progression of such secondary complications that determines the morbidity and

44

mortality associated with diabetes. A complication associated with diabetes that has

45

significant implications with respect to nutritional status in nephropathy, which

46

constitutes 44% of documented kidney failure cases in the United States according to

47

the National Institute of Diabetes and Digestive and Kidney Disease 2. In addition to its

48

role in the filtration of waste and toxins, the kidney is critical for nutrient reabsorption.

49

Thus, it is not surprising that compromised kidney function can lead to vitamin D

50

deficiency because vitamin D, as 25-hydroxycholecalciferol (25D), is reabsorbed or

51

activated to 1,25-dihydroxycholecalciferol in the kidney. Uptake of 25D by the renal

52

proximal tubular cells is dependent on the internalization of the 25D-vitamin D binding

53

protein (DBP) complex by the endocytic receptor proteins, megalin and cubilin, as well

54

as the adaptor protein disabled-2 3, 4. We have previously demonstrated that excessive

55

urinary excretion of 25D and DBP due to reduced kidney function led to compromised

56

vitamin D status in type 2 diabetic (T2D) rats 5. Therefore, it is not surprising that low

57

vitamin D status has been consistently linked with diabetes 6-8. Furthermore, several

58

studies have demonstrated that like diabetes, suboptimal vitamin D levels are linked to

59

an increased prevalence of bone disease, autoimmune disorders, and various types of

60

cancer 9-11. Because of the diverse biological actions of vitamin D, maintaining kidney


Page 4 of 29

Page 5 of 29


61

health in diabetes for maintenance of vitamin D balance could be critical to the

62

prevention of secondary complications that are associated with low vitamin D status.

63 64

We have recently reported that the inclusion of high-amylose maize (HAM), which

65

contains ~35% of type 2 resistant starch (RS2), as a substitute for cornstarch in the

66

AIN-93G diet, promoted renal health and vitamin D balance in animal models of type 1

67

diabetes (T1D) 12 and T2D 13, 14. While T2D is characterized by insulin resistance, T1D

68

is usually mediated by an autoimmune response and is characterized by dysfunctional

69

or destroyed pancreatic beta cells. There are multiple reports that suggest vitamin D

70

has an important immunomodulatory role 15-17. In addition, low vitamin D status was

71

associated with increased incidence of T1D 16, 17 and microalbuminuria in T1D patients

72

18, 19

73

unknown, our laboratory observed that rats fed RS prior to STZ injection exhibited

74

normal vitamin D balance and attenuated nephropathy 12. Specifically, we found that

75

RS-feeding reduced urinary excretion of 25D and DBP and normalized renal expression

76

of megalin and disabled-2 12. These findings suggest that the inclusion of RS into the

77

diet could be an effective means to prevent aberrant vitamin D metabolism.

. Although the causal relationship between vitamin D and T1D remains largely

78 79

RS is a class of fermentable carbohydrates that has been shown to improve insulin

80

sensitivity and reduce abdominal adiposity in obesity-related diabetes 20-22. RS2 in

81

particular is abundant in raw starchy vegetables and fruits such as potato and unripe

82

banana. The source of RS2 in our previous work was HAM, which contains an amylose-

83

extender mutant that allows the maize to contain a higher concentration of amylose, and



84

thus it is more resistant to enzymatic hydrolysis 23. RS2 from HAM is highly fermentable

85

by gut microbiota 24, 25 and has been shown to reduce adiposity and postprandial

86

glycemic response in obese animals 21, 22, 26. We reported that feeding rats HAM prior to

87

the induction of diabetes by STZ prevented nephropathy and vitamin D imbalance. The

88

objectives of the current study, therefore, were to: 1) determine whether feeding HAM to

89

rats following the induction of T1D could promote renal health and vitamin D balance

90

and 2) whether these effects could be produced by feeding T1D rats lower doses of

91

RS2 than we have utilized previously.

92

93

MATERIALS AND METHODS

94

Chemicals and assay kits. Streptozotocin was purchased from Sigma Aldrich (St.

95

Louis, MO). Creatinine assay kit was purchased from Cayman Chemical (Ann Arbor,

96

MI). Rat albumin and DBP ELISA kits were obtained from Innovative Research (Novi,

97

MI) and Life Diagnostic Inc (West Chester, PA), respectively. 25-hydroxycholelcalciferol

98

EIA kit was purchased from Immunodiagnostic Systems (Boldon, United Kingdom).

99 100

Animals and Diets. All procedures and protocols performed were approved by the

101

Institutional Animal Care and Use Committee at Iowa State University and in

102

compliance with Iowa State University Laboratory Animal Resources Guidelines. Male

103

Sprague-Dawley (SD) rats were purchased at 4 wk of age from Harlan (Indianapolis, IN)

104

and were housed individually in plastic flat-bottomed cages with free access to food and

105

water. Diet ingredients (AIN-93G) were purchased from Harlan Teklad (Indianapolis,

106

IN), whereas high-amylose maize (Amylogel®) was obtained from Cargill. To induce 5 ACS Paragon Plus Environment

Page 6 of 29

Page 7 of 29


107

T1D, streptozotocin (STZ, 60 mg/kg) in 10 mM citrate buffer (pH 4.5) was injected into

108

the intraperitoneal cavity (i.p.) of SD rats at 5 wk of age. Non-diabetic control SD rats

109

(NDC) (n = 8) were injected with an equal volume of citrate buffer. NDC rats were then

110

fed the AIN-93G diet, which contains cornstarch at a level of 550 g/kg diet.

111

Hyperglycemia in STZ-treated rats was confirmed 3-day post-STZ injection where blood

112

glucose concentrations were 30-50% higher compared to NDC rats. Then, all diabetic

113

rats were randomly assigned to 4 groups (n = 8/group) and fed AIN-93G diet, which

114

contained either 550 g/kg of corn starch (CS), high dose of HAM at 550 g/kg of HAM

115

(HRS), medium dose of HAM at 275 g/kg + 275 g/kg of corn starch (MRS), or low dose

116

of HAM at 138 g/kg + 412 g/kg of corn starch (LRS) for 4 weeks. All diets were prepared

117

as previously described and RS content was analyzed as we have previously reported

118

12, 13

119

digestion. Thus, the final RS content in the LRS, MRS, and HRS diets was 5%, 10%,

120

and 20%, respectively. Prior to the termination of study, all rats were fasted overnight

121

for 12 h in individual metabolic cages and urine was collected then frozen at -20°C until

122

analysis. Prior to the collection of blood and tissues, rats were anesthetized with a

123

ketamine: xylazine cocktail (90: 10 mg/kg BW) that was injected i.p. Whole blood was

124

then collected via cardiac puncture and an aliquot was kept in EDTA-coated vacutainer

125

at 4°C for glycated hemoglobin analysis. The remaining blood was stored in a serum

126

tube and allowed to clot at room temperature for 15 min prior to centrifugation at 2000 ×

127

g for 15 min. Serum was transferred into a microcentrifuge tube and kept at -20°C until

128

analysis.

. Our analysis revealed that the HAM used for this study was 35% resistant to

129



130

Assessment of blood glucose, hemoglobin A1c, and serum insulin. Blood glucose

131

was measured using a glucometer (Bayer Healthcare, Mississauga, Canada) at the time

132

of euthanasia. Glycated hemoglobin % (HbA1c %) was measured in whole blood

133

samples within 48 h of sacrifice with a commercial kit (Stanbio, Boerne, TX). Serum

134

insulin concentrations were measured with a commercial ELISA kit (EMD Millipore,

135

Billerica, MA).

136 137

Assessment of urinary creatinine, urinary albumin, and vitamin D status. Urinary

138

creatinine, albumin, DBP, and 25D as well as serum 25D were assessed using

139

commercially available kits as we have reported previously 5, 12, 13. Total urinary

140

excretion of albumin, DBP, and 25D over 12 h was normalized to urinary creatinine as

141

previously reported 5, 12, 13.

142 143

Assessment of serum pro-inflammatory markers. Serum TNF-α (R&D systems,

144

Minneapolis, MN) and serum IL-6 (Thermo Scientific, Waltham, MA) were analyzed via

145

commercial ELISA kits. Data were expressed as fold changes relative to NDC rats.

146 147

Statistical analyses. Data were analyzed with Statistical Analysis System (SAS 9.4)

148

using one-way ANOVA followed by a Fisher Least Square Difference post-hoc test.

149

Outliers were detected by Mixed Model Influential Diagnostics and removed if internal

150

studentized residuals outside the interval of [-2.5, 2.5]. Correlation analysis was

151

assessed between fasting blood glucose concentrations, urinary DBP, urinary 25D, and


Page 8 of 29

Page 9 of 29


152

serum IL-6 concentrations by a Pearson Product-Moment Correlation test. Significance

153

of all tests was set at P ≤ 0.05.

154

155

RESULTS

156

Body weight, blood glucose, and kidney function. When combined, all T1D rats

157

gained significantly less weight than NDC rats throughout the 4 wk treatment period,

158

(Fig. 1). CS rats gained 65% less weight than the NDC rats, but no differences in weight

159

gain were detected between the CS and LRS. However, MRS- and HRS-fed T1D rats

160

gained approximately 52% and 73% more weight, respectively, compared to CS rats

161

(Fig. 1). Although RS normalized growth patterns in the T1D rats in a dose-dependent

162

manner, fasting blood glucose concentrations, hemoglobin A1c%, and insulin levels

163

were not affected by RS diets (Table 1). In addition, both urinary creatinine and albumin

164

in T1D rats were ~3- to 5.5-fold lower, and ~4- to 6-fold greater compared to NDC rats,

165

respectively, but did not differ among the RS-fed T1D rats (Table 1).

166 167

Vitamin D status. Urinary excretion of DBP was 21- to 32-fold greater in T1D rats

168

compared to NDC rats. LRS, MRS, and HRS diets reduced excretion of DBP by 15%,

169

36%, 32% in T1D rats, respectively, when compared to CS rats (Fig. 2A). All T1D rats

170

excreted 3.5- to 6-fold higher amount of 25D in the urine compared to control rats, but

171

no differences were detected between the T1D rats regardless of dietary RS content

172

(Fig. 2B). Urinary excretion of 25D and DBP had no impact on vitamin D status in T1D

173

rats. Serum 25D concentrations in T1D rats were between 33 - 45% higher than in NDC

174

rats regardless of dietary RS content (Fig. 2C). In addition, the relative food intake of 8 ACS Paragon Plus Environment


175

T1D rats was approximately 56 – 72% greater than the NDC rats (data not shown), and

176

that the average daily intake of vitamin D was ~2-fold higher in T1D rats compared to

177

NDC rats (Fig. 2D).

178 179

Circulating IL-6 and TNF-α concentrations. Because a pro-inflammatory state is

180

highly associated with the development of microvascular complications in diabetes, we

181

assessed the effect of RS on the secretion of pro-inflammatory cytokines, TNF-α and IL-

182

6 in T1D animals. Overall, LRS and HRS rats, but not MRS rats, have greater serum IL-

183

6 concentrations NDC and CS rats (Supplemental Fig. 1A). On the contrary, we did not

184

detect any differences in circulating TNF-α among all groups (Supplemental Fig. 1B).

185 186

Correlation between hyperglycemia, urinary 25D, DBP, and circulating IL-6

187

concentrations. Urinary DBP (r = 0.798, P < 0.001) and urinary 25D (r = 0.518, P =

188

0.02) concentrations were positively correlated with blood glucose concentrations,

189

respectively. Additionally, circulating IL-6, but not TNF-α, was strongly correlated with

190

hyperglycemia (r = 0.472; P = 0.02) (Fig. 3). No correlation was identified between IL-6,

191

vitamin D status, and renal function.

192

193

DISCUSSION

194

In the present study, we demonstrated that inclusion of dietary RS normalized the

195

growth pattern of STZ-induced T1D rats. Because the total weight gain in both MRS-

196

and HRS-fed T1D rats did not differ from the CS rats, we estimate that the minimal

197

effective dose that can impact the growth of T1D rats is 10% RS in the diet. Body weight 9 ACS Paragon Plus Environment

Page 10 of 29

Page 11 of 29


198

fluctuation is a common symptom of T1D. Our study revealed that dietary RS

199

attenuated the catabolic nature of uncontrolled T1D, which indicates that though a

200

number of parameters did not differ between RS-treated and CS-fed T1D rats, these

201

results suggest that RS-fed T1D rats exhibited better overall health. Interestingly, the

202

growth pattern improvement in RS-fed rats was independent of hyperglycemia and

203

vitamin D status, and was not associated with inflammation status as serum IL-6

204

concentrations in these rats were still significantly higher than in CS rats. However,

205

since our study was limited to the measurement of two pro-inflammatory cytokines,

206

TNF-α and IL-6, we recognize that a full inflammatory panel may reveal that other

207

factors play a larger role with respect to inflammation status in our animal model.

208 209

We have previously reported that feeding rats HAM prior to induction of T1D normalized

210

growth patterns and attenuated urinary excretion of 25D and serum proteins 12. Based

211

on these observations, we hypothesized that the renoprotective effect of dietary RS may

212

have partially contributed to the overall weight maintenance because the RS-fed T1D

213

rats were less diabetic and therefore likely retained calories from glucose and protein.

214

Interestingly, our results show that though growth stunting was attenuated by RS in a

215

dose-dependent manner, growth rate appeared to be independent of kidney function

216

since no differences were detected in urinary creatinine or urinary albumin between

217

groups. It is still unclear why our current observations were in contrast with our previous

218

study showing that dietary RS, when introduced prior to the induction of T1D,

219

attenuated urinary loss of vitamin D and maintained renal integrity in STZ-induced

220

diabetic rats 12. It is possible that the persistent state of hyperglycemia in the T1D rats



221

due to rapid destruction of beta cells may have exacerbated the progression of kidney

222

damage to a stage that cannot be reversed by dietary RS. Thus, another likelihood with

223

respect to the normalized growth pattern in T1D rats by RS could be the influence on

224

the secretion of glucagon-like protein 1 (GLP-1) and peptide YY, the gut hormones that

225

are known to mediate postprandial satiety. Dietary RS has been reported to enhance

226

GLP-1 and peptide YY secretion in vivo 27. GLP-1 has also been shown to enhance

227

beta cell proliferation and insulin secretion. Hence, GLP-1 agonists have been widely

228

used as a co-treatment for T1D and T2D to delay the progression of diabetes and

229

attenuate diabetic symptoms 28-30. Therefore, it is possible that RS enhanced insulin

230

secretion via a GLP-1-mediated pathway, which in turn could have promoted energy

231

retention and growth in T1D rats. Additionally, because RS2 is a class of fermentable

232

fiber, it is very likely that feeding RS before the induction of diabetes may have altered

233

the microbial composition of the gut. We hypothesize this based on reports that short

234

chain fatty acids production or other products of fermentation can provide protection

235

against nephropathy 31-33. In fact, it has been shown that modulation of the gut

236

microflora through the supplementation of probiotics and fermentable fibers reduced the

237

incidence of T1D 34, 35 and chronic kidney disease 36, 37, suggesting that the composition

238

of the microbiome can, at least in part, modulate the risk of T1D development and

239

complications that occur during its progression.

240 241

Diabetes nephropathy has been shown to increase the risk for vitamin D deficiency and

242

thus the development of vitamin D-associated complications in diabetes due to the

243

critical role of kidney in vitamin D activation 5, 14, 38, 39. More recently, vitamin D status


Page 12 of 29

Page 13 of 29


244

has been inversely associated with the incidence of both T1 and T2D 16, 17. In support of

245

these observations, we have demonstrated that the increase of blood glucose

246

concentrations was strongly correlated with excessive excretions of urinary 25D and

247

DBP, which suggest that perturbation of vitamin D balance in T1D rats could be a result

248

of hyperglycemia. Intriguingly, even though T1D rats excreted higher amounts of 25D

249

and DBP, vitamin D status, as indicated by serum 25D concentrations, it was still

250

greater in all diabetic groups compared to control rats. Since we observed hyperphagia

251

in T1D rats, a likely explanation for the increase in serum 25D concentrations is that a

252

higher intake of vitamin D compensated for the urinary excretion of 25D. As we

253

expected to observe at least moderate amelioration of diabetic symptoms in rats with

254

higher serum concentrations of 25D, our current data showed that vitamin D status in

255

T1D rats had no impact on circulating pro-inflammatory cytokines, fasting blood

256

glucose, or HbA1c%. Similar to the current study, Shih et al. 40 reported that correction

257

of vitamin D deficiency had no effect on inflammation and other diabetic symptoms in

258

adolescents with T1D. It is possible that the onset of nephropathy or other diabetic

259

complications promoted oxidative stress and an inflammatory state in the T1D rats used

260

in our studies, which may have confounded the protective effect of vitamin D. In support

261

of this concept, we showed that RS did not improve glucose metabolism in T1D rats

262

while serum IL-6 concentrations, a pro-inflammatory cytokine, were strongly correlated

263

with hyperglycemia. Consistent with our findings, Jaacks et al 41 reported that dietary

264

fiber intake among youth who were diagnosed with T1D was not associated with

265

systemic inflammation. In contrast, C-reactive protein and fibrinogen concentrations, the

266

positive acute-phase proteins secreted in response to inflammation, were inversely



267

correlated with fiber consumption in non-diabetic adolescents 42, indicating that the

268

mechanism by which dietary fiber such as RS impacts inflammation could be dependent

269

on glycemic status.

270 271

One limitation of this study was associated with the RS intervention window. We

272

designed the current experiment based upon our previous experiences that 2 weeks of

273

RS intervention attenuated kidney damage in STZ-induced T1D rats 12. Because STZ

274

causes rapid weight loss and nephropathy as a result of hyperglycemia, we began the

275

RS treatment 3-day post STZ injection that lasted only for 4 weeks. It is assumed that

276

the current approach would allow sufficient time frame for RS to exert protection in T1D

277

rats while preventing compromised health in the control diabetic rats.

278 279

Here, we confirmed that the time at which dietary RS is introduced is critical with

280

respect to providing nephroprotection in T1D. This may also partially explain our

281

observation that kidney health, and thus vitamin D balance, was protected in T1D rats

282

when RS was given prior to the induction of diabetes 12. In line with our observations,

283

others have reported that the protective actions of 1,25D in T1D were most effective

284

when treatment was given at weaning (prior to insulitis onset) rather than when insulitis

285

was already present 43-45. Hence, our future work will focus on the development of

286

preventative strategies with RS that will delay or prevent the onset of diabetic

287

nephropathy and secondary complications associated with suboptimal levels of vitamin

288

D.

289


Page 14 of 29

Page 15 of 29


290

ABBREVIATIONS

291

25D, 25-hydroxycholecalciferol; CS, Type 1 diabetic rats fed AIN-93G diet; DBP,

292

Vitamin D binding protein; GLP-1, Glucagon-like protein 1; HAM, high-amylose maize;

293

HbA1c Glycated hemoglobin; HRS, Type 1 diabetic rats fed AIN-93G diet containing

294

20% RS; IL-6, Interleukin-6; LRS, Type 1 diabetic rats fed AIN-93G diet containing 5%

295

RS; MRS, Type 1 diabetic rats fed AIN-93G diet containing 10% RS; NDC: Non-diabetic

296

control; RS, resistant starch; SD, Sprague-Dawley; STZ, Streptozotocin; T1D, Type 1

297

diabetes; T2D, Type 2 diabetes; TNF-α: Tumor necrosis factor-α

298 299

ACKNOWLEDGEMENTS

300

G.Y.K. designed the study and performed all aspects of animal maintenance,

301

experimental diets preparation, laboratory experiments, as well as drafted the original

302

version of this manuscript. M.J.R and K.L.S. assisted with the study design. K.G. and

303

Y.T.L. assisted in animal maintenance and laboratory procedure. All authors have read

304

and approved the final version of this manuscript.

305 306

SUPPORTING INFORMATION

307

Supplemental Fig. 1. RS elevated circulating IL-6, but not TNF-α in T1D rats.

308 309

SUPPORTING INFORMATION

310

The authors declare no competing financial interest.

311



312

REFERENCES

313

1.

314

(September 29, 2016)

315

2.

316

(Feb 27, 2016)

317

3.

318

R., Mutually dependent localization of megalin and Dab2 in the renal proximal tubule.

319

Am. J Physiol. Renal Physiol. 2005, 289, F569-76.

320

4.

321

F.; Christensen, E. I.; Willnow, T. E., An endocytic pathway essential for renal uptake

322

and activation of the steroid 25-(OH) vitamin D3. Cell 1999, 96, 507-15.

323

5.

324

homeostasis is compromised due to increased urinary excretion of the 25-

325

hydroxycholecalciferol-vitamin D-binding protein complex in the Zucker diabetic fatty rat.

326

Am. J Physiol. Endocrinol. Metabol. 2010, 299, E959-67.

327

6.

328

Z.; Sikaris, K.; Ebeling, P. R.; Daly, R. M., Low serum 25-hydroxyvitamin D is

329

associated with increased risk of the development of the metabolic syndrome at five

330

years: results from a national, population-based prospective study (The Australian

331

Diabetes, Obesity and Lifestyle Study: AusDiab). J Clin. Endocrinol. Metabol. 2012, 97,

332

1953-61.

Statistics About Diabetes. http://www.diabetes.org/diabetes-basics/statistics/.

Diseases, N. I. D. D. K. Kidney Disease of Diabetes. www.kidney.niddk.nih.gov

Nagai, J.; Christensen, E. I.; Morris, S. M.; Willnow, T. E.; Cooper, J. A.; Nielsen,

Nykjaer, A.; Dragun, D.; Walther, D.; Vorum, H.; Jacobsen, C.; Herz, J.; Melsen,

Anderson, R. L.; Ternes, S. B.; Strand, K. A.; Rowling, M. J., Vitamin D

Gagnon, C.; Lu, Z. X.; Magliano, D. J.; Dunstan, D. W.; Shaw, J. E.; Zimmet, P.


Page 16 of 29

Page 17 of 29


333

7.

334

D insufficiency improves insulin sensitivity in obese adolescents: a randomized

335

controlled trial. Am. J Clin. Nutr. 2013, 97, 774-81.

336

8.

337

Nuboer, R.; de Boer, F. K.; van den Ham, H. J.; Kalkhoven, E.; Prakken, B.; Schipper,

338

H. S., Vitamin D deficiency in childhood obesity is associated with high levels of

339

circulating inflammatory mediators, and low insulin sensitivity. Int J Obes. (Lond.) 2014,

340

38, 46-52.

341

9.

342

Rutten, E.; Pittas, A. G.; Boland, R.; Ferrucci, L.; Bikle, D. D., Vitamin D: beyond bone.

343

Ann. N. Y. Acad. Sci. 2013, 1287, 45-58.

344

10.

345

408-25.

346

11.

347

F.; Lieben, L.; Mathieu, C.; Demay, M., Vitamin D and human health: lessons from

348

vitamin D receptor null mice. Endocr. Rev. 2008, 29, 726-76.

349

12.

350

M.; Rowling, M. J., Dietary resistant starch prevents urinary excretion of 25-

351

hydroxycholecalciferol and vitamin D-binding protein in type 1 diabetic rats. J. Nutr.

352

Belenchia, A. M.; Tosh, A. K.; Hillman, L. S.; Peterson, C. A., Correcting vitamin

Reyman, M.; Verrijn Stuart, A. A.; van Summeren, M.; Rakhshandehroo, M.;

Christakos, S.; Hewison, M.; Gardner, D. G.; Wagner, C. L.; Sergeev, I. N.;

Zittermann, A.; Gummert, J. F., Nonclassical vitamin D action. Nutrients 2010, 2,

Bouillon, R.; Carmeliet, G.; Verlinden, L.; van Etten, E.; Verstuyf, A.; Luderer, H.

Smazal, A. L.; Borcherding, N. C.; Anderegg, A. S.; Schalinske, K. L.; Whitley, E.

2013, 143, 1123-8.

353

13.

Koh, G. Y.; Whitley, E. M.; Mancosky, K.; Loo, Y. T.; Grapentine, K.; Bowers, E.;

354

Schalinske, K. L.; Rowling, M. J., Dietary resistant starch prevents urinary excretion of



355

vitamin D metabolites and maintains circulating 25-hydroxycholecalciferol

356

concentrations in Zucker diabetic fatty rats. J. Nutr. 2014, 144, 1667-73.

357

14.

358

Wisecup, E.; Schalinske, K. L.; Rowling, M. J., Circulating Adiponectin Concentrations

359

are Increased by Dietary Resistant Starch and Correlate with Serum 25-

360

Hydroxycholecalciferol Concentrations and Kidney Function in Zucker Diabetic Fatty

361

Rats. Nutr. Res. 2016, 36, 311-319.

362

15.

363

proliferation of naive CD8+ T cells and development of CD8 mediated gastrointestinal

364

inflammation. BMC Immunol. 2014, 15, 6.

365

16.

366

Bayer, M.; Hintermann, E.; Pfeilschifter, J. M.; Badenhoop, K.; Ramos-Lopez, E.;

367

Christen, U., Influence of the vitamin D plasma level and vitamin D-related genetic

368

polymorphisms on the immune status of patients with type 1 diabetes: a pilot study.

369

Clin. Exp. Immunol. 2013, 171, 171-85.

370

17.

371

Obermayer-Pietsch, B. M.; Pieber, T. R., The effect of vitamin D supplementation on

372

peripheral regulatory T cells and beta cell function in healthy humans: a randomized

373

controlled trial. Diabetes Metab. Res Rev. 2011, 27, 942-5.

374

18.

375

Molitch, M. E.; Steffes, M. W.; Sun, W.; Zinman, B.; Brunzell, J. D., Circulating vitamin D

376

metabolites and kidney disease in type 1 diabetes. J. Clin. Endocrinol. Metabol. 2012,

377

97, 4780-8.

Koh, G. Y.; Derscheid, R.; Fuller, K. N. Z.; Valentine, R. J.; Leow, S. E.; Reed, L.;

Chen, J.; Bruce, D.; Cantorna, M. T., Vitamin D receptor expression controls

Rose, K.; Penna-Martinez, M.; Klahold, E.; Karger, D.; Shoghi, F.; Kahles, H.;

Bock, G.; Prietl, B.; Mader, J. K.; Holler, E.; Wolf, M.; Pilz, S.; Graninger, W. B.;

de Boer, I. H.; Sachs, M. C.; Cleary, P. A.; Hoofnagle, A. N.; Lachin, J. M.;


Page 18 of 29

Page 19 of 29


378

19.

Dutta, D.; Choudhuri, S.; Mondal, S. A.; Mukherjee, S.; Chowdhury, S., Urinary

379

albumin : creatinine ratio predicts prediabetes progression to diabetes and reversal to

380

normoglycemia: role of associated insulin resistance, inflammatory cytokines and low

381

vitamin D. J. Diabetes 2014, 6, 316-22.

382

20.

383

Resistant starch improves insulin sensitivity in metabolic syndrome. Diabet Med. 2010,

384

27, 391-7.

385

21.

386

Q., High-amylose rice improves indices of animal health in normal and diabetic rats.

387

Plant Biotechnol. J. 2012, 10, 353-62.

388

22.

389

Todd, E.; Jones, C. K.; Tulley, R. T.; Melton, S.; Martin, R. J.; Hegsted, M., Effects of

390

resistant starch, a non-digestible fermentable fiber, on reducing body fat. Obesity (Silver

391

Spring) 2006, 14, 1523-34.

392

23.

393

amylose-extender (ae) mutant starches: Part II. Structures and properties of starch

394

residues remaining after enzymatic hydrolysis at boiling-water temperature. Carbohydr.

395

Polym. 2010, 80, 1-12.

396

24.

397

K. L.; Pelkman, C.; Tulley, R.; Goita, M.; Durham, H. A.; Zhou, J.; Senevirathne, R. N.,

398

Resistant starch from high amylose maize (HAM-RS2) reduces body fat and increases

399

gut bacteria in ovariectomized (OVX) rats. Obesity (Silver Spring) 2013, 21, 981-4.

Johnston, K. L.; Thomas, E. L.; Bell, J. D.; Frost, G. S.; Robertson, M. D.,

Zhu, L.; Gu, M.; Meng, X.; Cheung, S. C.; Yu, H.; Huang, J.; Sun, Y.; Shi, Y.; Liu,

Keenan, M. J.; Zhou, J.; McCutcheon, K. L.; Raggio, A. M.; Bateman, H. G.;

Jiang, H. C., Mark; Blanco, Mike; Jane, Jay-Lin, Characterization of maize

Keenan, M. J.; Janes, M.; Robert, J.; Martin, R. J.; Raggio, A. M.; McCutcheon,



400

25.

Conlon, M. A.; Kerr, C. A.; McSweeney, C. S.; Dunne, R. A.; Shaw, J. M.; Kang,

401

S.; Bird, A. R.; Morell, M. K.; Lockett, T. J.; Molloy, P. L.; Regina, A.; Toden, S.; Clarke,

402

J. M.; Topping, D. L., Resistant starches protect against colonic DNA damage and alter

403

microbiota and gene expression in rats fed a Western diet. J. Nutr. 2012, 142, 832-40.

404

26.

405

improves insulin resistance and reduces adipose tissue weight and CD11c expression

406

in rat OLETF adipose tissue. Nutrition 2014, 30, 590-5.

407

27.

408

Danna, S. C.; Tripathy, S.; Hegsted, M.; Keenan, M. J., Dietary resistant starch

409

upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation

410

in rodents. Am. J Physiol. Endocrinol. Metabol. 2008, 295, E1160-6.

411

28.

412

Immunol 2013, 149, 317-23.

413

29.

414

Esposito, K.; Giugliano, D.; Genovese, S., Glucagon-like peptide 1 reduces endothelial

415

dysfunction, inflammation, and oxidative stress induced by both hyperglycemia and

416

hypoglycemia in type 1 diabetes. Diabetes Care 2013, 36, 2346-50.

417

30.

418

peptide-1 plasma levels, as a possible adaptive response, in diabetic NOD mice.

419

Biochem. Biophys. Res. Commun. 2012, 423, 583-7.

420

31.

421

beta-cell proliferation, function and glucose homeostasis through modulation of

Harazaki, T.; Inoue, S.; Imai, C.; Mochizuki, K.; Goda, T., Resistant starch

Zhou, J.; Martin, R. J.; Tulley, R. T.; Raggio, A. M.; McCutcheon, K. L.; Shen, L.;

Pettus, J.; Hirsch, I.; Edelman, S., GLP-1 agonists in type 1 diabetes. Clin

Ceriello, A.; Novials, A.; Ortega, E.; Canivell, S.; La Sala, L.; Pujadas, G.;

Rydgren, T.; Borjesson, A.; Carlsson, A.; Sandler, S., Elevated glucagon-like

Khan, S.; Jena, G. B., Protective role of sodium butyrate, a HDAC inhibitor on


Page 20 of 29

Page 21 of 29


422

p38/ERK MAPK and apoptotic pathways: study in juvenile diabetic rat. Chem. Biol.

423

Interact. 2014, 213, 1-12.

424

32.

425

H.; Kieffer, D. A.; Adams, S. H.; Martin, R. J., High amylose resistant starch diet

426

ameliorates oxidative stress, inflammation, and progression of chronic kidney disease.

427

PloS one 2014, 9, e114881.

428

33.

429

Vitto, M. F.; Cesconetto, P. A.; de Souza, C. T.; Ritter, C.; Dal-Pizzol, F., Sodium

430

butyrate decreases the activation of NF-kappaB reducing inflammation and oxidative

431

damage in the kidney of rats subjected to contrast-induced nephropathy. Nephrol. Dial.

432

Transplantation 2012, 27, 3136-40.

433

34.

434

modulated by restricted flora not germ-free conditions. PloS one 2011, 6, e17049.

435

35.

436

Sorensen, S. J.; Buschard, K.; Hansen, A. K., Early life treatment with vancomycin

437

propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD

438

mouse. Diabetologia 2012, 55, 2285-94.

439

36.

440

T.; Chonan, O.; Nangaku, M., Galacto-oligosaccharides attenuate renal injury with

441

microbiota modification. Physiol. Reports 2014, 2.

442

37.

443

Peterson, D. A.; Rabb, H., Intestinal microbiota-kidney cross talk in acute kidney injury

444

and chronic kidney disease. Nephron. Clinical practice 2014, 127, 139-43.

Vaziri, N. D.; Liu, S. M.; Lau, W. L.; Khazaeli, M.; Nazertehrani, S.; Farzaneh, S.

Machado, R. A.; Constantino Lde, S.; Tomasi, C. D.; Rojas, H. A.; Vuolo, F. S.;

King, C.; Sarvetnick, N., The incidence of type-1 diabetes in NOD mice is

Hansen, C. H.; Krych, L.; Nielsen, D. S.; Vogensen, F. K.; Hansen, L. H.;

Furuse, S. U.; Ohse, T.; Jo-Watanabe, A.; Shigehisa, A.; Kawakami, K.; Matsuki,

Noel, S.; Martina-Lingua, M. N.; Bandapalle, S.; Pluznick, J.; Hamad, A. R.;



445

38.

Agarwal, R., Vitamin D, Proteinuria, Diabetic Nephropathy, and Progression of

446

CKD. Clin J Am Soc Nephro 2009, 4, 1523-1528.

447

39.

448

D levels, microvascular complications, and mortality in type 1 diabetes. Diabetes Care

449

2011, 34, 1081-5.

450

40.

451

Effects of vitamin D repletion on glycemic control and inflammatory cytokines in

452

adolescents with type 1 diabetes. Pediatr. Diabetes 2014.

453

41.

454

D.; D'Agostino, R. B., Jr.; Dolan, L. M.; Marcovina, S.; Reynolds, K.; Shah, A. S.;

455

Urbina, E. M.; Wadwa, R. P.; Mayer-Davis, E. J., No association of dietary fiber intake

456

with inflammation or arterial stiffness in youth with type 1 diabetes. J. Diabetes

457

Complications 2014, 28, 305-10.

458

42.

459

Y., Adolescent fiber consumption is associated with visceral fat and inflammatory

460

markers. Am. J Physiol. Endocrinol. Metabol. 2012, 97, E1451-7.

461

43.

462

Bouillon, R.; Eizirik, D. L.; Mathieu, C., 1,25-Dihydroxyvitamin D3 modulates expression

463

of chemokines and cytokines in pancreatic islets: implications for prevention of diabetes

464

in nonobese diabetic mice. Endocrinology 2005, 146, 1956-64.

465

44.

466

Bouillon, R., Prevention of type I diabetes in nonobese diabetic mice by late intervention

Joergensen, C.; Hovind, P.; Schmedes, A.; Parving, H. H.; Rossing, P., Vitamin

Shih, E. M.; Mittelman, S.; Pitukcheewanont, P.; Azen, C. G.; Monzavi, R.,

Jaacks, L. M.; Crandell, J.; Liese, A. D.; Lamichhane, A. P.; Bell, R. A.; Dabelea,

Parikh, S.; Pollock, N. K.; Bhagatwala, J.; Guo, D. H.; Gutin, B.; Zhu, H.; Dong,

Gysemans, C. A.; Cardozo, A. K.; Callewaert, H.; Giulietti, A.; Hulshagen, L.;

Casteels, K. M.; Mathieu, C.; Waer, M.; Valckx, D.; Overbergh, L.; Laureys, J. M.;


Page 22 of 29

Page 23 of 29


467

with nonhypercalcemic analogs of 1,25-dihydroxyvitamin D3 in combination with a short

468

induction course of cyclosporin A. Endocrinology 1998, 139, 95-102.

469

45.

470

diabetes in NOD mice by nonhypercalcemic doses of a new structural analog of 1,25-

471

dihydroxyvitamin D3, KH1060. Endocrinology 1995, 136, 866-72.

Mathieu, C.; Waer, M.; Casteels, K.; Laureys, J.; Bouillon, R., Prevention of type I

472

473



474

Figure Captions

475

Fig. 1. Dietary RS attenuated body weight loss at a dose-dependent manner in

476

T1D rats. STZ was injected i.p. at Day 0 and all rats were fed experimental diets for 4

477

wks starting on Day 1 as indicated in Materials and Methods. NDC, non-diabetic rats fed

478

a AIN-93G diet; CS, T1D rats fed AIN-93G diet; LRS, T1D rats fed AIN-93G diet

479

containing 5% RS; MRS, T1D rats fed AIN-93G diet containing 10% RS; HRS, T1D rats

480

fed AIN-93G diet containing 20% RS. Baseline body weight gain is indicated as pre-

481

streptozotocin (STZ) injection. Data are means ± SEM (n = 8/group). Groups with

482

different letters differ (P < 0.05).

483

484

Fig 2. Dietary RS attenuated urinary DBP, but had no impact on serum 25D

485

concentrations in T1D rats. A) Urinary DBP, B) urinary 25D, C) serum 25D, D) mean

486

daily intake of vitamin D in NDC, CS, LRS, MRS, and HRS. All rats were fed

487

experimental diets for 4 wks as indicated in Materials and Methods. NDC, non-diabetic

488

rats fed AIN-93G diet; CS, T1D rats fed AIN-93G diet; LRS, T1D rats fed AIN-93G diet

489

containing 5% RS; MRS, T1D rats fed AIN-93G diet containing 10% RS; HRS, T1D rats

490

fed AIN-93G diet containing 20% RS. Baseline body weight gain is indicated as pre-

491

streptozotocin (STZ) injection. Data are means ± SEM (N = 6-8/group). Groups with

492

different letters differ (P < 0.05).

493 494

Fig 3. Hyperglycemia was positively correlated with excessive excretion of DBP

495

and 25D and serum IL-6 levels. A) Urinary DBP, B) urinary 25D, and C) circulating IL-


Page 24 of 29

Page 25 of 29


496

6 concentrations were strongly correlated to fasting blood glucose concentrations. Each

497

symbol represents data for an individual rat (n = 20 – 25).

498



Page 26 of 29

499

Table 1. Glucose homeostasis and kidney function in NDC, CS, LRS, MRS, and HRS

500

following 4 wks of treatment1 NDC

CS

LRS

MRS

HRS

108 ± 8.7a

598 ± 134b

636 ± 95b

472 ± 91b

535 ± 103b

Hemoglobin A1c, %

3.84 ± 0.67a

6.08 ± 0.67ab

6.51 ± 1.20b

5.62 ± 1.13ab

5.87 ± 0.63ab

Insulin, ng/mL

1.65 ± 0.33b

0.83 ± 0.07a

0.72 ± 0.02a

0.94 ± 0.08a

0.97 ± 0.06a

Urinary creatinine, mg/dL

67.34 ± 7.99

12.31 ± 0.79

15.59 ± 1.87

20.36 ± 2.48

23.49 ± 7.42

Urinary albumin, ng/mg of creatinine

17.59 ± 6.09

79.82 ± 14.58

90.36 ± 9.49

63.93 ± 9.38

105.23 ± 25.32

Fasting blood glucose, mg/dL

501

1

502

different letters are differ, P ≤ 0.05. All rats were fed experimental diets for 4 wks as

503

indicated in Materials and Methods. NDC, non-diabetic rats fed AIN-93G diet; CS, T1D

504

rats fed AIN-93G diet; LRS, T1D rats fed AIN-93G diet containing 5% RS; MRS, T1D

505

rats fed AIN-93G diet containing 10% RS; HRS, T1D rats fed AIN-93G diet containing

506

20% RS.

Data are expressed as mean ± SEM (n = 6 – 8). Mean values across the row with

507 508 509 510


Page 27 of 29

511


Figure 1.

512

225

Body Weight Gain (g)

200 175 150

a

NDC CS LRS MRS HRS

b

125

bc

100 75

cd d

50 25 0

-9 -6 -3 513

Post-STZ

Pre-STZ

0

3

6

9

12 15 18 21 24 27 30

Day

514



515

Page 28 of 29

Figure 2.

516

519 520

ab

25 b

20 15 10

525 526 527

b

60 a

50 40 30

10

c

0

CS

LRS

MRS

NDC

HRS

CS

LRS

MRS

HRS

300 Urinary 25D (pmol/mg of creatinine)

524

b

20

5

NDC

523

C

b b

70

ab

0

521 522

80

a

Serum 25D (nmol/L)

518

A 30

B

a

250

a

200

a

150 a

100 50

b

Mean Daily Vitamin D Intake (IU)

517

Urinary DBP (ng/mg of creatinine)

35

0 NDC

CS

LRS

MRS

70 60

a

50 40

b

30 3

HRS

D

NDC CS LRS MRS HRS

80

6

9

12

15 Day


18

21

24

27

30

Page 29 of 29


A

Urinary DBP (ng/mg of creatinine)

40 30 20 10

Pearson's r = 0.798 (P < 0.001)

0

Urinary 25D (pmol/mg of creatinine)

B 300

200

100 Pearson's r = 0.518 (P = 0.02)

Serum IL-6 Concentrations (pg/mL)

0

C

1000

Pearson's r = 0.472 (P = 0.02)

900 800 700 600 500 400 0

528

150

300

450

600

750

900

1050 1200

Fasting Blood Glucose Concentrations (mg/dL)

529


Consumption of Dietary Resistant Starch Partially ... - ACS Publications

Recommend Documents