The role of gut hormones in glucose homeostasis

Abstract

The gastrointestinal tract has a crucial role in the control of energy homeostasis through its role in the digestion, absorption, and assimilation of ingested nutrients. Furthermore, signals from the gastrointestinal tract are important regulators of gut motility and satiety, both of which have implications for the long-term control of body weight. Among the specialized cell types in the gastrointestinal mucosa, enteroendocrine cells have important roles in regulating energy intake and glucose homeostasis through their actions on peripheral target organs, including the endocrine pancreas. This article reviews the biological actions of gut hormones regulating glucose homeostasis, with an emphasis on mechanisms of action and the emerging therapeutic roles of gut hormones for the treatment of type 2 diabetes mellitus.

Figure 1. Actions of selected peptides on key tissues important for the control of glucose homeostasis.

Both GLP1 and GIP promote insulin biosynthesis, insulin secretion, and islet β cell survival. GLP1 exerts additional actions important for regulation of glucose homeostasis, including inhibition of glucagon secretion and gastric emptying, and induction of satiety. GIP, but not GLP1, directly engages receptors on adipocytes coupled to energy storage. In contrast, CCK and gastrin do not seem to acutely regulate levels of plasma glucose but might be important for stimulating the formation of new β cells by stimulating islet neogenesis.