EFFECTS OF GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE AND GLUCAGON-LIKE PEPTIDE-I-(7-36) ON INSULIN-SECRETION

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like p eptide (GLP)-I-(7-36) are probably the most important ''incretins,'' b ut there is controversy as to their relative insulinotropic activities . The effects of natural (np) and synthetic porcine (sp) GIP, syntheti c human (sh) GIP, and GLP-I-(7-36) on insulin secretion from the per f used rat pancreas were compared using gradient perfusion. Insulin secr etion was increased by both spGIP and GLP-I-(7-36) at concentrations o f similar to 16 pM. Maximal responses to GLP-I-(7-36) in the presence of 16.7 mM glucose were slightly greater than with npGIP or spGIP, but with 10 mM glucose spGIP and GLP-I-(7-36) exerted equivalent effects. Responses to shGIP were greatly reduced compared with spGIP. In the p resence of 50 pM spGIP or GLP-I-(7-36) the glucose threshold was 4.5 /- 0.11 mM. The data indicate that GLP-I-(7-36) and porcine GIP are eq ually insulinotropic and share the same glucose threshold for activity , whereas shGIP is less active. At the concentrations found postprandi ally, however, GIP is likely to be the more important incretin.