The Paradoxical Role of Glucose-Dependent Insulinotropic Polypeptide (GIP) in Diet and Eating Behaviour in Health and Disease

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is an intestinal hormone released in response to nutrient intake - mainly carbohydrate and fat. In health it has a number of well-known biological effects, which include stimulation of insulin secretion and maintenance of B-cell mass. However, type 2 diabetes mellitus is characterised by a state of B-cell resistance to GIP. Extrapancreatic receptors for GIP have been demonstrated in a variety of tissues suggesting that it may have important biological effects beyond the pancreas. Of particular interest, GIP peptide/receptor systems may also be present in the brain, suggesting that this peptide may have important biological effects in central pathways. High fat intake leads to hyperplasia of GIP producing intestinal cells, hypersecretion of GIP and the loss of normal inhibitory effect of insulin upon fat-stimulated GIP release, properties that led to it being described as an obesity hormone more than 20 years ago. It is therefore being recognized that GIP receptor blockade may attenuate obesity induced by a high-fat diet. On the other hand GIP agonists also appear to benefit glucose metabolism in obesity and diabetes. The apparent paradox that both pro-GIP and anti-GIP strategies have been shown to be beneficial requires resolution. Since GIP has significant effects on carbohydrate and fat metabolism the GIP pathway may a target for anti-obesity therapies.