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  • Title: Effect of glucagon-like peptide-1 on alpha- and beta-cell function in C-peptide-negative type 1 diabetic patients.
    Author: Kielgast U, Asmar M, Madsbad S, Holst JJ.
    Journal: J Clin Endocrinol Metab; 2010 May; 95(5):2492-6. PubMed ID: 20207828.
    Abstract:
    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 alpha- and beta-cell responses to GLP-1 in type 1 diabetic patients without residual beta-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 x 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 x min (P < 0.001). In addition, GLP-1 decreased the arginine-stimulated glucagon release (incremental AUC of 103 +/- 21 and 137 +/- 16 pmol/liter x 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.
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