GIP Does Not Potentiate the Antidiabetic Effects of GLP-1 in Hyperglycemic Patients With Type 2 Diabetes
| Autor: | Nikolaos Mentis, Michael A. Nauck, Juris J. Meier, Carolyn F. Deacon, Lars D. Köthe, Jens J. Holst, Michael J. Theodorakis, Irfan Vardarli |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male endocrine system medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Incretin Gastric Inhibitory Polypeptide Type 2 diabetes Incretins Pathophysiology Glucagon Gastric inhibitory polypeptide Glucagon-Like Peptide 1 Diabetes mellitus Internal medicine Internal Medicine medicine Humans Hypoglycemic Agents Drug Interactions Aged business.industry Insulin digestive oral and skin physiology Middle Aged medicine.disease Glucagon-like peptide-1 Endocrinology Diabetes Mellitus Type 2 Gastrointestinal hormone Hyperglycemia Female business hormones hormone substitutes and hormone antagonists |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db10-1332 |
| Popis: | OBJECTIVE The incretin glucagon-like peptide 1 (GLP-1) exerts insulinotropic activity in type 2 diabetic patients, whereas glucose-dependent insulinotropic polypeptide (GIP) no longer does. We studied whether GIP can alter the insulinotropic or glucagonostatic activity of GLP-1 in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Twelve patients with type 2 diabetes (nine men and three women; 61 ± 10 years; BMI 30.0 ± 3.7 kg/m2; HbA1c 7.3 ± 1.5%) were studied. In randomized order, intravenous infusions of GLP-1(7-36)-amide (1.2 pmol · kg−1 · min−1), GIP (4 pmol · kg−1 · min−1), GLP-1 plus GIP, and placebo were administered over 360 min after an overnight fast (≥1 day wash-out period between experiments). Capillary blood glucose, plasma insulin, C-peptide, glucagon, GIP, GLP-1, and free fatty acids (FFA) were determined. RESULTS Exogenous GLP-1 alone reduced glycemia from 10.3 to 5.1 ± 0.2 mmol/L. Insulin secretion was stimulated (insulin, C-peptide, P < 0.0001), and glucagon was suppressed (P = 0.009). With GIP alone, glucose was lowered slightly (P = 0.0021); insulin and C-peptide were stimulated to a lesser degree than with GLP-1 (P < 0.001). Adding GIP to GLP-1 did not further enhance the insulinotropic activity of GLP-1 (insulin, P = 0.90; C-peptide, P = 0.85). Rather, the suppression of glucagon elicited by GLP-1 was antagonized by the addition of GIP (P = 0.008). FFA were suppressed by GLP-1 (P < 0.0001) and hardly affected by GIP (P = 0.07). CONCLUSIONS GIP is unable to further amplify the insulinotropic and glucose-lowering effects of GLP-1 in type 2 diabetes. Rather, the suppression of glucagon by GLP-1 is antagonized by GIP. |
| Databáze: | OpenAIRE |
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