Glucose-dependent insulinotropic polypeptide as a regulator of beta cell function and fate.
Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that is secreted in response to food intake and modulates beta cell function. It may also regulate beta cell fate. Released from the nutrient-sensing K-cells of the upper intestine, GIP acts on various tissues, including pancreatic beta cells, via interaction with its G-protein-coupled receptor. Perhaps the most important effect of GIP is its potentiation of insulin secretion. Indeed, pharmacological blockade or genetic knockout of its receptor delays glucose-dependent insulin secretion. Exposure to GIP also enhances the beta cell response to future nutrient stimulation and upregulates transcription of key beta cell genes. There is emerging evidence that like the related hormone glucagon-like peptide-1, GIP may function as a beta cell growth factor and anti-apoptotic agent, further supporting a role for this hormone in balancing beta cell function to changing metabolic conditions. Overproduction of GIP in response to increased nutrient loads may, however, contribute to the pathophysiology of obesity. Interestingly, its insulinotropic effect is lost in type 2 diabetes, perhaps because of hyperglycemia-induced receptor desensitization. A better understanding of GIP's effects on the beta cell under normal and pathological conditions may facilitate the design of GIP derivatives for the treatment of metabolic disorders.
Wideman
R D
RD
Departments of Physiology and Surgery, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada.
Kieffer
T J
TJ
D017209:Apoptosis / Q000502:physiology; D003920:Diabetes Mellitus / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology*; D009765:Obesity / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism / Q000502:physiology*
D007328:Insulin; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor