Consumption of Dietary Resistant Starch Partially Corrected the

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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

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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.

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Journal of Agricultural and Food Chemistry

TYPE 1 DIABETES

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Consumption of Dietary Resistant Starch Partially Corrected the Growth Pattern

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despite Hyperglycemia and Compromised Kidney Function in Streptozotocin-

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induced Diabetic Rats

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

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Ting Loo§

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†

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University, Ames, Iowa, United States.

The Interdepartmental Graduate Program in Nutritional Sciences, Iowa State

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§

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50011, United States.

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¥

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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

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*Corresponding author:

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Gar Yee Koh, Ph.D.

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Vitamins and Carcinogenesis Laboratory,

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

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

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Tel: +1 617 556 3222

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E-mail: [email protected]

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ABSTRACT

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

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induction of diabetes delayed the progression of diabetic nephropathy and maintained

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

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

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

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

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

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

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

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

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

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

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Streptozotocin; type 1 diabetes; resistant starch; vitamin D

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INTRODUCTION

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

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uncontrolled, diabetes typically leads to severe macrovascular and microvascular

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

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

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

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significant implications with respect to nutritional status in nephropathy, which

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

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

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

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

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

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18, 19

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

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

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

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

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

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

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

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

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

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

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



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

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

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

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

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

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

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

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RS2 than we have utilized previously.

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MATERIALS AND METHODS

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

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

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

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

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

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

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

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compliance with Iowa State University Laboratory Animal Resources Guidelines. Male

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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12, 13

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

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

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

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

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

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

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

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

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

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analysis.

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

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

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

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

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

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

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Billerica, MA).

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

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

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

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

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previously reported 5, 12, 13.

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

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

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

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

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

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

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

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


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

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of all tests was set at P ≤ 0.05.

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RESULTS

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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NDC rats (Fig. 2D).

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

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

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

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

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

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

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

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

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0.02) concentrations were positively correlated with blood glucose concentrations,

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

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

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vitamin D status, and renal function.

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DISCUSSION

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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



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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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microflora through the supplementation of probiotics and fermentable fibers reduced the

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

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

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complications that occur during its progression.

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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



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

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

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on glycemic status.

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

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

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

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

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

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

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rats while preventing compromised health in the control diabetic rats.

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

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

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

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

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

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

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

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

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nephropathy and secondary complications associated with suboptimal levels of vitamin

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D.

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ABBREVIATIONS

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

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

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

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

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

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

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

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ACKNOWLEDGEMENTS

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

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

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

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

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and approved the final version of this manuscript.

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SUPPORTING INFORMATION

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

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SUPPORTING INFORMATION

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The authors declare no competing financial interest.

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

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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 Corrected the

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