Pathophysiology of type 2 diabetes: targeting islet cell dysfunction

Abstract

Type 2 diabetes mellitus (T2DM) continues to be a major health problem worldwide. It is well known that T2DM is a metabolic disorder characterized by hyperglycemia, which arises from insufficient pancreatic insulin secretion, insulin resistance in peripheral tissues, and inadequate suppression of glucagon production. This suppression results in inadequate uptake, storage, and disposal of ingested glucose accompanied by elevated hepatic production of glucose and profound hyperglycemia. Notably, these pathophysiologic processes can progress to a clinically significant degree even in patients with impaired glucose tolerance. As researchers begin to unravel the genetic basis of T2DM, the gradual accumulation of genetic polymorphisms in multiple genes-rather than the mutation of a single "diabetes gene"-appears to be the driving force behind the increase in T2DM risk. Emergent therapies for the management of T2DM include incretin-based agents, which can effectively target two key processes in T2DM by augmenting insulin secretion and inhibiting glucagon production.