Effect of glucolipotoxicity and rosiglitazone upon insulin secretion.

Type 2 diabetes is characterised by elevated blood glucose and fatty acid concentrations, and aberrant expression of exocytotic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Restoration of normoglycaemia is often accomplished through use of the thiazolidinedione drug rosiglitazone (RSG), although little is known of its actions on the pancreas. Here we report that high glucose resulted in 96.

Calpain-10: from genome search to function.

Calpain-10 (CAPN10) is the first diabetes gene to be identified through a genome scan. Many investigators, but not all, have subsequently found associations between CAPN10 polymorphism and type 2 diabetes (T2D) as well as insulin action, insulin secretion, aspects of adipocyte biology and microvascular function. However, this has not always been with the same single nucleotide polymorphism (SNP) or haplotype or the same phenotype, suggesting that there might be more than one disease-associated CAPN10 variant and that these might vary between ethnic groups and the phenotype under study.

Polymorphic variations in the neurogenic differentiation-1, neurogenin-3, and hepatocyte nuclear factor-1alpha genes contribute to glucose intolerance in a South Indian population.

The neurogenic differentiation-1 (NEUROD1), neurogenin-3 (NEUROG3), and hepatic nuclear factor-1alpha (TCF1) genes are interacting transcription factors implicated in controlling islet cell development and insulin secretion. Polymorphisms of these genes (Ala45Thr [NEUROD1], Ser199Phe [NEUROG3], and Ala98Val [TCF1]) have been postulated to influence the development of type 2 diabetes. We have investigated the role and interaction between these variants using PCR/restriction fragment-length polymorphism assays in 454 subjects recruited as part of a population survey in South India.

Haplotype combinations of calpain 10 gene polymorphisms associate with increased risk of impaired glucose tolerance and type 2 diabetes in South Indians.

Haplotype combination 112/121 and its intrinsic variants (UCSNP43, -19, and -63) identified within the calpain 10 gene are associated with increased risk of type 2 diabetes in Mexican-Americans. We evaluated whether this haplotype combination and its constituent haplotypes and variants contribute to increased susceptibility to impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) and type 2 diabetes in a South Indian population. Two study groups were used: 95 families ascertained through a proband with type 2 diabetes and 468 subjects recruited as part of an urban survey (69.