Effect of Glucagon-Like Peptide-1 on α- and β-Cell Function in C-Peptide-Negative Type 1 Diabetic Patients

• Published in: The journal of clinical endocrinology and metabolism Vol. 95; no. 5; pp. 2492 - 2496
• Main Authors: Kielgast, Urd, Asmar, Meena, Madsbad, Sten, Holst, Jens J.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-05-2010; Copyright by The Endocrine Society
• Subjects: Arginine - pharmacology; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; C-Peptide - blood; C-Peptide - drug effects; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Glucagon - antagonists & inhibitors; Glucagon - secretion; Glucagon-Like Peptide 1 - pharmacology; Glucagon-Like Peptide 1 - secretion; Glucagon-Secreting Cells - drug effects; Glucagon-Secreting Cells - physiology; Humans; Hyperglycemia - blood; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - physiology; Medical sciences; Serum Albumin - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Human; Immunopathology; Obesity; Cell function; Nutrition; Nutrition disorder; Peptide hormone; Autoimmune disease; Patient; Metabolic diseases; C-Peptide; Glucagon like peptide 1; Gastrointestinal hormone; Type 1 diabetes; β Cell; Endocrinology; Nutritional status
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2009-2440

Context: The mechanism by which glucagon-like peptide-1 (GLP-1) suppresses glucagon secretion is uncertain, and it is not determined whether endogenous insulin is a necessary factor for this effect.
Objective: To characterize the α- and β-cell responses to GLP-1 in type 1 diabetic patients without residual β-cell function.
Methods: Nine type 1 diabetic patients, classified as C-peptide negative by a glucagon test, were clamped at plasma glucose of 20 mmol/liter for 90 min with arginine infusion at time 45 min and concomitant infusion of GLP-1 (1.2 pmol/kg · min) or saline.
Results: Infusion with GLP-1 increased C-peptide concentration just above the detection limit of 33 pmol/liter in one patient, but C-peptide remained immeasurable in all other patients. In the eight remaining patients, total area under the curve of glucagon was significantly decreased with GLP-1 compared with saline: 485 ± 72 vs. 760 ± 97 pmol/liter · min (P < 0.001). In addition, GLP-1 decreased the arginine-stimulated glucagon release (incremental AUC of 103 ± 21 and 137 ± 16 pmol/liter · min, with GLP-1 and saline, respectively, P < 0.05).
Conclusions: In type 1 diabetic patients without endogenous insulin secretion, GLP-1 decreases the glucagon secretion as well as the arginine-induced glucagon response during hyperglycemia. GLP-1 induced endogenous insulin secretion in one of nine type 1 diabetic patients previously classified as being without endogenous insulin secretion.
GLP-1 suppressed glucagon levels in type 1 diabetic patients without endogenous insulin secretion and induced endogenous insulin secretion in one out of nine type 1 diabetic patients.