RESPONSE OF TRUNCATED GLUCAGON-LIKE PEPTIDE-1 AND GASTRIC-INHIBITORY POLYPEPTIDE TO GLUCOSE-INGESTION IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS - EFFECT OF SULFONYLUREA THERAPY

Gastric inhibitory polypeptide (GIP) and truncated glucagon like pepti de-1 (tGLP-1) are potent gastrointestinal insulinotropic factors (incr etin), mostly released after a meal or ingestion of glucose in man and animals. To investigate whether sulfonylurea (SU) affects the secreti on of incretin, the modulation of plasma GIP and tGLP-1 levels followi ng glucose ingestion in non-insulin-dependent diabetic type 2 patients with or without SU therapy was studied. A 75-g oral glucose tolerance test (OGTT) was carried out on 9 healthy subjects (controls) and 18 p atients with non-obese type 2, 9 of whom were treated by diet alone (N IDDM-diet) and the other 9 with SU (glibenclamide 2.5 mg or gliclazide 40 mg) once a day (NIDDM-SU). Plasma GIP was measured by radioimmunoa ssay (RIA) with R65 antibody, and GLP-1 was measured by RIA with N-ter minal-directed antiserum R1043 (GLP-1NT) and C-terminal-directed antis erum R2337 (GLP-1CT). Following OGTT, plasma glucose, GIP, GLP-1NT, an d GLP-1CT in type 2 patients increased more markedly than in controls, despite the lower response of insulin. However, there were no signifi cant differences in plasma levels of these peptides between the NIDDM- diet and NIDDM-SU groups. Therefore, it is unlikely that SU is involve d in the high response of GIP and GLP-1s to OGTT in type 2 patients.