[Diabetogenes; which cause type II diabetes mellitus]

Glucose homeostasis depends upon a balance between glucose production by the liver and glucose utilization by insulin-dependent tissues, such as muscle and fat. Insulin, secreted by the pancreatic B cell, inhibits hepatic glucose output and facilitates glucose utilization in the muscle and fat tissues. In the diabetic patients, there are three types of pathological defects; (1) inability of the B cell to secrete normal insulin in an accurate fashion, (2) increase in the hepatic glucose output, and (3) decrease in glucose metabolism at the muscle and fat tissues. Candidate genes which cause the first defect are the insulin gene, the glucokinase gene and the mitochondrial tRNA gene. The glucokinase gene causes the second defect, too. Those which cause the third defect are the insulin receptor gene and glycogen synthase gene. However, these genes in total account for 3% or less of type II diabetes. Further analyses of systems of both insulin secretion and insulin receptor-signaling at a molecular level will help elucidate the other diabetes candidate genes.