Effect of glucagon-like peptide-1 on alpha- and beta-cell function in C-peptide-negative type 1 diabetic patients

J Clin Endocrinol Metab. 2010 May;95(5):2492-6. doi: 10.1210/jc.2009-2440. Epub 2010 Mar 5.

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.

MeSH terms

  • Arginine / pharmacology
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • C-Peptide / blood*
  • C-Peptide / drug effects
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Glucagon / antagonists & inhibitors
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glucagon-Secreting Cells / drug effects
  • Glucagon-Secreting Cells / physiology*
  • Humans
  • Hyperglycemia / blood
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / physiology*
  • Serum Albumin / pharmacology

Substances

  • Blood Glucose
  • C-Peptide
  • Serum Albumin
  • Glucagon-Like Peptide 1
  • Glucagon
  • Arginine