DISTINCTIVE CHARACTERISTICS OF INSULIN-GLUCOSE METABOLISM IN INTRAUTERINE GROWTH RESTRICTED AND IMPAIRED GLUCOSE TOLERANCE NONHUMAN PRIMATES

Abstract

There are many studies in animal models showing associations between intrauterine growth restriction (IUGR) and the development of type 2 diabetes mellitus. However little was done on non-human primate, a model that is closely related to human. This thesis investigates any differences in metabolic gene expression levels, physical and biochemical characteristics between normal and impaired glucose tolerance (IGT) adult cynomolgus macaques, and between normal and IUGR offspring. IGT macaques were 60% higher in body mass index, 22% deceased in glucose clearance rate and hyperinsulinemia. Gene expression analysis showed 1.25-1.4 fold increase in AKT1, AKT2 & MSTN, and 2.3-2.8 fold decrease in IRS1 & SLC2A4RG. IUGR neonates were 10% lighter in birth weight and experienced a `catch-up growth¿ in the first 3 months. At 15 months, they had a higher glucose clearance rate, 3-6 fold decrease in AKT1, AKT2 & MSTN, and 1.9-7.7 fold increase in PIK3R1, IRS1 & SLC2A4RG. After 9 months high fat diet treatment, IUGR macaques exhibited similar progression with adult IGT macaques in gene expression. All these demonstrate accelerated insulin glucose metabolism in IUGR subjects at young, and developed symptoms of impaired glucose tolerant faster than normal subjects in later life, after subjected to an unhealthy diet.