Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in Type 2 (non-insulin-dependent) diabetic patients

Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in Type... 125 36 36 8 8 Dr. M. A. Nauck N. Kleine C. Ørskov J. J. Holst B. Willms W. Creutzfeldt Division of Gastroenterology and Endocrinology, Department of Medicine Georg-August-University Göttingen Germany Fachklinik für Diabetes und Stoffwechselkrankheiten Bad Lauterberg Germany Departments of Anatomy B and Physiology C Panum Institute Copenhagen Denmark Medizinische Klinik der Ruhr-Universität im Knappschafts-Krankenhaus In der Schornau 23-25 D-44892 Bochum Germany Summary Glucagon-like peptide 1 (GLP-1) (7-36 amide) is a physiological incretin hormone that is released after nutrient intake from the lower gut and stimulates insulin secretion at elevated plasma glucose concentrations. Previous work has shown that even in Type 2 (non-insulin-dependent) diabetic patients GLP-1 (7-36 amide) retains much of its insulinotropic action. However, it is not known whether the magnitude of this response is sufficient to normalize plasma glucose in Type 2 diabetic patients with poor metabolic control. Therefore, in 10 Type 2 diabetic patients with unsatisfactory metabolic control (HbA lc 11.6±1.7%) on diet and sulphonylurea therapy (in some patients supplemented by metformin or acarbose), 1.2 pmol ×kg −1 ×min −1 GLP-1 (7-36 amide) or placebo was infused intravenously in the fasting state (plasma glucose 13.1±0.6 mmol/l). In all patients, insulin (by 17.4±4.7 nmol ×1 −1 ×min; p =0.0157) and C-peptide (by 228.0±39.1 nmol×1 −1 ×min; p =0.0019) increased significantly over basal levels, glucagon was reduced (by -1418±308 pmol ×1 −1 ×min) and plasma glucose reached normal fasting concentrations (4.9±0.3 mmol/l) within 4 h of GLP-1 (7-36 amide) administration, but not with placebo. When normal fasting plasma glucose concentrations were reached insulin returned towards basal levels and plasma glucose concentrations remained stable despite the ongoing infusion of GLP-1 (7-36 amide). Therefore, exogenous GLP-1 (7-36 amide) is an effective means of normalizing fasting plasma glucose concentrations in poorly-controlled Type 2 diabetic patients. The glucose-dependence of insulinotropic actions of GLP-1 (7-36 amide) appears to be retained in such patients. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Diabetologia Springer Journals

Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in Type 2 (non-insulin-dependent) diabetic patients

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Publisher
Springer Journals
Copyright
Copyright © 1993 by Springer-Verlag
Subject
Medicine & Public Health; Human Physiology; Internal Medicine; Metabolic Diseases
ISSN
0012-186X
eISSN
1432-0428
D.O.I.
10.1007/BF00401145
Publisher site
See Article on Publisher Site

Abstract

125 36 36 8 8 Dr. M. A. Nauck N. Kleine C. Ørskov J. J. Holst B. Willms W. Creutzfeldt Division of Gastroenterology and Endocrinology, Department of Medicine Georg-August-University Göttingen Germany Fachklinik für Diabetes und Stoffwechselkrankheiten Bad Lauterberg Germany Departments of Anatomy B and Physiology C Panum Institute Copenhagen Denmark Medizinische Klinik der Ruhr-Universität im Knappschafts-Krankenhaus In der Schornau 23-25 D-44892 Bochum Germany Summary Glucagon-like peptide 1 (GLP-1) (7-36 amide) is a physiological incretin hormone that is released after nutrient intake from the lower gut and stimulates insulin secretion at elevated plasma glucose concentrations. Previous work has shown that even in Type 2 (non-insulin-dependent) diabetic patients GLP-1 (7-36 amide) retains much of its insulinotropic action. However, it is not known whether the magnitude of this response is sufficient to normalize plasma glucose in Type 2 diabetic patients with poor metabolic control. Therefore, in 10 Type 2 diabetic patients with unsatisfactory metabolic control (HbA lc 11.6±1.7%) on diet and sulphonylurea therapy (in some patients supplemented by metformin or acarbose), 1.2 pmol ×kg −1 ×min −1 GLP-1 (7-36 amide) or placebo was infused intravenously in the fasting state (plasma glucose 13.1±0.6 mmol/l). In all patients, insulin (by 17.4±4.7 nmol ×1 −1 ×min; p =0.0157) and C-peptide (by 228.0±39.1 nmol×1 −1 ×min; p =0.0019) increased significantly over basal levels, glucagon was reduced (by -1418±308 pmol ×1 −1 ×min) and plasma glucose reached normal fasting concentrations (4.9±0.3 mmol/l) within 4 h of GLP-1 (7-36 amide) administration, but not with placebo. When normal fasting plasma glucose concentrations were reached insulin returned towards basal levels and plasma glucose concentrations remained stable despite the ongoing infusion of GLP-1 (7-36 amide). Therefore, exogenous GLP-1 (7-36 amide) is an effective means of normalizing fasting plasma glucose concentrations in poorly-controlled Type 2 diabetic patients. The glucose-dependence of insulinotropic actions of GLP-1 (7-36 amide) appears to be retained in such patients.

Journal

DiabetologiaSpringer Journals

Published: Aug 1, 1993

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