The role of gastrointestinal hormones in the pathogenesis of obesity and type 2 diabetes

Abstract

Obesity, influencing the increase of incidence of type 2 diabetes, cardiovascular complications and cancer is a growing medical problem worldwide. The feelings of hunger and satiety are stimulated by the "gut-brain axis", where a crucial role is played by gastrointestinal hormones: glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, pancreatic polypeptide, peptide YY, oxyntomodulin, cholecystokinin and ghrelin. These hormones affect not only the functioning of the digestive tract, but also might have effects on insulin secretion and are mediators which affect brain areas involved in the regulation of food intake. The effect of their actions can be antagonistic as well as an additive or synergistic, and their secretion is dependent on many factors, such as dietary nutrients or the energy state of the body. Changes in circulating gut hormones concentrations result in activation of various pathways primarily within the hypothalamus and brain stem areas, which modulate feeding behaviour and a number of metabolic processes.

Keywords: diabetes; gut hormones; obesity.

Figure 1

Hunger/satiety regulation in CNS (“gut-brain axis”) ---I anorectic effect, → orexigenic/stimulatory effect, NPY – neuropeptide Y, AgRP – Agouti-related peptide, POMC – proopiomelanocortin, CART – cocaine- and amphetamine-regulated transcript, GLP-1 – glucagon-like peptide-1, GIP – glucosedependent insulinotropic peptide, PP – pancreatic polypeptide, PYY – peptide YY, OXM – oxyntomodulin

Figure 2

Mean 24-hour plasma ghrelin profiles in normal-weight and obese subjects (modified by Cummings et al. NEJM 2002) [9]

Figure 3

Changes in plasma PYY3-36 concentration after ingestion meals with varying content of protein/fat/carbohydrate (by El Khoury et al. Eur J Nutr 2010) [46]

Figure 4

Post-translational products of proglucagon: A – proglucagon; B – products of alternative splicing in pancreas; C – products of alternative splicing in intestine and brain (by Kieffer et al. Endocr Rev 1999) [69]

Figure 5

The main effects of GLP-1 actions (based on Baggio, Drucker, Gastroenterology 2007) [72]