Degree Type

Thesis

Date of Award

2014

Degree Name

Master of Science

Department

Food Science and Human Nutrition

First Advisor

Kevin Schalinske

Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by abnormal carbohydrate metabolism, insulin deficiency and subsequent hyperglycemia. Complications arise with poor glycemic control leading to the onset of microvascular and macrovascular diseases. Advanced glycation end products (AGEs) associated with hyperglycemia infiltrate microvascular tissues, ultimately leading to vascular disease of the nervous system, eyes and kidneys.1 Diabetic nephropathy is the leading cause of chronic kidney disease.2 The severity of this autoimmune disease is therefore independently and dependently associated with numerous pathologies such as cardiovascular disease, vitamin D deficiency and impaired one-carbon metabolism.

CKD is characterized by structural and functional changes of the glomerulus and renal tubules, which results in impaired filtration and reabsorption of various proteins and nutrients involved in methyl group metabolism and vitamin D metabolism. Declining glomerular filtration associated with renal disease is associated with hyperfiltration of vitamin D binding protein (DBP) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), disrupting vitamin D status and decreased homocysteine clearance and subsequent plasma homocysteine elevation.3-5 Understanding the mechanisms that mediate methyl group supply and homocysteine regulation is imperative in the prevention and treatment of these interrelated chronic diseases.

Alterations in key regulatory proteins within one-carbon metabolism have been observed in type 1 diabetes as compensatory mechanisms for disturbed homocysteine levels and methyl group supply. Previous research has demonstrated normalization of glycine N-methyltransferase (GNMT) and other regulatory proteins associated with administration of insulin, glucocorticoids and retinoic acid (RA). These results indicate the potential role of hormonal modulation in regulating one-carbon pathways.6 In addition, we have implemented the use of resistant starch (RS) in our laboratory as a therapeutic dietary agent for glycemic control in diabetes. In these studies, we have demonstrated the ability of RS to prevent and/or alleviate many DM-related complications including weight loss, hyperglycemia and diabetic nephropathy. In addition, RS-treatment normalized gene expression of proteins involved in vitamin D metabolism.

These results have illustrated the protective effect of RS in diabetes, specifically related to diabetic nephropathy and associated perturbations in vitamin D metabolism. The goal of this study was to investigate the effect of dietary RS in preventing/attenuating abnormalities related to diabetes perturbed methyl group metabolism. Furthermore, this study aimed to explore the possibility of RS and glucose as potential hormonal and nutritional modulators in methyl group metabolism using a streptozotocin (STZ)-induced model of T1DM.

Copyright Owner

Alysse S. Anderegg

Language

en

File Format

application/pdf

File Size

78 pages

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