Journal Article

Reduced Hepatic Insulin Extraction in Response to Gastric Inhibitory Polypeptide Compensates for Reduced Insulin Secretion in Normal-Weight and Normal Glucose Tolerant First-Degree Relatives of Type 2 Diabetic Patients

Helmut J. Rochlitz, Andreas F.H. Pfeiffer, Natalia N. Rudovich

2004

Overview

Reduced Hepatic Insulin Extraction in Response to Gastric Inhibitory Polypeptide Compensates for Reduced Insulin Secretion in Normal-Weight and Normal Glucose Tolerant First-Degree Relatives of Type 2 Diabetic Patients Natalia N. Rudovich , Helmut J. Rochlitz and Andreas F.H. Pfeiffer From the Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, and the Department of Endocrinology, Diabetes and Nutrition, Campus B. Franklin, Charite University Medicine, Berlin, Germany Address correspondence and reprint requests to Andreas F.H. Pfeiffer, German Institute of Human Nutrition Potsdam-Rehbrücke, Department of Clinical Nutrition, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany. E-mail: afhp{at}mail.dife.de Abstract Our objective was to study whether young first-degree relatives of patients with type 2 diabetes (FDRs) have altered insulin secretion and insulin clearance in response to gastric inhibitory polypeptide (GIP) in combination with glucose and arginine. A hyperglycemic clamp (11.1 mmol/l for 115 min), followed by addition of GIP (2 pmol · kg −1 · min −1 , 60–115 min) and an arginine bolus and infusion (10 mg · kg −1 · min −1 , 90–115 min), was conducted on 14 healthy volunteers and 13 FDRs. Both groups had normal glucose tolerance. FDRs were more insulin resistant (HOMA IR ) under basal conditions ( P = 0.003). FDRs demonstrated significant global impairment in insulin secretion capacity, which was not specific for one of the secretagogues. Insulin clearance was significantly reduced in the group of FDRs under basal conditions and in response to GIP, but there was no general defect in insulin clearance in response to glucose and arginine. The HOMA IR correlated negatively ( P < 0.01) with insulin clearance under basal conditions ( r = −0.96) and under GIP infusion ( r = −0.56). We propose that impairment in insulin secretion capacity and decreased insulin sensitivity is compensated for several mechanisms, one of which includes a GIP-dependent reduction of the insulin clearance that will increase peripheral insulin levels to maintain normoglycemia. AUC, area under the curve FDRs, first-degree relative of patient with type 2 diabetes GIP, gastric inhibitory polypeptide GLP, glucagon-like peptide HOMA, homeostasis model assessment IR, insulin resistance ISR, insulin secretion rate MCR, metabolic clearance rate Footnotes Accepted June 2, 2004. Received September 30, 2003. DIABETES

• Publisher: American Diabetes Association
• Subject: Adult / Arginine - administration & dosage / Biological and medical sciences / Blood Glucose / Body Weight / Diabetes Mellitus, Type 2 - genetics / Diabetes Mellitus, Type 2 - metabolism / Diabetes Mellitus, Type 2 - physiopathology / Diabetes. Impaired glucose tolerance / Diagnosis / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Family Health / Female / Gastric Inhibitory Polypeptide - administration & dosage / Glucose - administration & dosage / Glucose Clamp Technique / Glucose Tolerance Test / Humans / Hyperglycemia - genetics / Hyperglycemia - metabolism / Hyperglycemia - physiopathology / Insulin - blood / Insulin - metabolism / Insulin Secretion / Liver - metabolism / Male / Medical sciences / Polypeptides / Services / Type 2 diabetes