Relationships among inositols, glucose tolerance, insulin sensitivity, and tyrosine phosphorylation of the insulin receptor
Abstract
The risk of developing impaired glucose tolerance (IGT) increases as a person ages. IGT is associated with insulin resistance and increases an older person's risk of developing diabetes mellitus. This dissertation contains two different research studies that evaluated the relationships among inositols, glucose tolerance, and tyrosine phosphorylation of the insulin receptor. Study 1: Previous research has evaluated various compounds in the urine that are related to insulin resistance. People with type 2 diabetes have a higher urinary excretion of D-chiro-inositol and myo-inositol, which has been linked to lower insulin sensitivity and higher indices of glucose tolerance. The purpose of this study was to evaluate the relationships between urinary inositol excretions and indices of glucose tolerance (plasma glucose, insulin, and C-peptide), insulin sensitivity, and skeletal muscle insulin receptor phosphorylation in 15 older, non-diabetic humans that were at risk for developing type 2 diabetes. The majority of the participants (67%) had IGT. The results from this study indicated that subjects with higher urinary D-chiro-inositol excretion had higher insulin (Rho = 0.51, p < 0.05) and C-peptide (Rho = 0.56, p < 0.05) area under the curves, and lower insulin sensitivity index (Rho = -0.60, p < 0.05) during the IVGTT. Urinary D-chiro-inositol (Rho = -0.60, p < 0.05) and myo-inositol (Rho = -0.60, p < 0.05) were inversely related to insulin receptor phosphotyrosine 1162/1163, but not related to insulin receptor total content during the OGTT. The apparent relationships were modestly weakened when adjustments were made for sex. This study supports previous research linking higher urinary D-chiro -inositol excretion with a decline in glucose tolerance and extends it to include a blunted activation of the tyrosine phosphorylation of the insulin receptor in the skeletal muscle. Study 2: Previous studies have evaluated supplements to prevent, delay, or improve diabetes mellitus. Some studies suggest that supplementing pinitol (methylated derivative of D-chiro-inositol) to people with type 2 diabetes improves glucose tolerance. However, conflicting results have been found. The purpose of this study was to assess the effects of acute pinitol supplementation on glucose tolerance and insulin sensitivity during fasting and oral glucose-stimulated hyperglycemic and hyperinsulinemic conditions in 15 older, non-diabetic humans. The majority of the participants (73%) had IGT. This study also evaluated the tyrosine phosphorylation of the insulin receptor in skeletal muscle. The results from this study documented that supplemented pinitol was absorbed into the bloodstream within 60 min, maintained in the bloodstream over a 240-min testing period, and excreted in urine. However, it did not acutely influence glucose tolerance, insulin sensitivity, and tyrosine phosphorylation of the insulin receptor in older, non-diabetic humans. Conclusion: An association was found between urinary D-chiro-inositol, insulin and C-peptide AUC, insulin sensitivity, and tyrosine phosphorylation of the insulin receptor, suggesting that urinary D-chiro-inositol may be indicative of insulin resistance and the progression towards type 2 diabetes. Also, pinitol supplementation was not found to be a potential treatment for glycemic control in an older, non-diabetic population at risk for developing diabetes.
Degree
Ph.D.
Advisors
Campbell, Purdue University.
Subject Area
Nutrition
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