Increased expression of adenylyl cyclase 3 in pancreatic islets and central nervous system of diabetic Goto-Kakizaki rats: a possible regulatory role in glucose homeostasis.

Adenylyl cyclase 3 (AC3) is expressed in pancreatic islets of the Goto-Kakizaki (GK) rat, a spontaneous animal model of type 2 diabetes (T2D), and also exerts genetic effects on the regulation of body weight in man. In addition to pancreatic islets, the central nervous system (CNS) plays an important role in the pathogenesis of T2D and obesity by regulating feeding behavior, body weight and glucose metabolism. In the present study, we have investigated AC3 expression in pancreatic islets, striatum and hypothalamus of GK rats to evaluate its role in the regulation of glucose homeostasis.

Distribution of neuropeptide Y Leu7Pro polymorphism in patients with type 1 diabetes and diabetic nephropathy among Swedish and American populations.

Objective: The distribution of Leu7Pro polymorphism in the neuropeptide Y gene shows a geographical north to south gradient of decreasing frequency, suggesting that it may be a population-specific causal variant. This polymorphism is found to be associated with diabetic nephropathy (DN) and coronary heart disease in Finnish women with type 1 diabetes (T1D). The present study aims to evaluate the susceptibility of this polymorphism to the development of DN in two different populations.

Genetic variation in receptor protein tyrosine phosphatase sigma is associated with type 2 diabetes in Swedish Caucasians.

Objective: Previously, it has been demonstrated that receptor protein tyrosine phosphatase sigma (RPTPsigma) is involved in glucose homeostasis and insulin signaling in several animal models. The aim of this study was to evaluate whether polymorphisms in this gene influence the development of type 2 diabetes (T2D) in humans.

Design: We investigated how genetic variations in the RPTPsigma gene influence susceptibility to impaired glucose tolerance (IGT) and T2D, in Swedish men and women.

Quantitative trait loci near the insulin-degrading enzyme (IDE) gene contribute to variation in plasma insulin levels.

Insulin-degrading enzyme (IDE) plays a principal role in the proteolysis of several peptides in addition to insulin and is encoded by IDE, which resides in a region of chromosome 10q that is linked to type 2 diabetes. Two recent studies presented genetic association data on IDE and type 2 diabetes (one positive and the other negative), but neither explored the fundamental question of whether polymorphism in IDE has a measurable influence on insulin levels in human populations. To address this possibility, 14 single nucleotide polymorphisms (SNPs) from a linkage disequilibrium block encompassing IDE have been genotyped in a sample of 321 impaired glucose tolerant and 403 nondiabetic control subjects.