Figure 4.

Schema of proposed integrated model representing the islet trihormonal abnormality hypothesis of type 2 diabetes. Upon ingestion of glucose, it is absorbed and simultaneously GIP is released into the circulation from which it interacts with α- (blue), β- (green), and PP cells (red). In type 2 diabetes, GIPRs on β-cells are not responsive to GIP and are therefore ineffective in enhancing insulin secretion response to glucose, even as plasma glucose level gets progressively higher. But GIPRs on α-cells are functional, and their activation causes increased glucagon secretion, unopposed by ineffective insulin secretion. This results in increased hepatic glucose output. GIPRs on PP cells are functional and their activation results in PP secretion. IR, insulin receptor.