Effect of glucagon-like peptide-1 on alpha- and beta-cell function in C-peptide-negative type 1 diabetic patients.
BACKGROUND
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.
Kielgast
Urd
U
Department of Biomedical Sciences, Panum Institute, University of Copenhagen, 2200 Copenhagen, Denmark. urd.kielgast@hvh.regionh.dk
Asmar
Meena
M
Madsbad
Sten
S
Holst
Jens J
JJ
D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000097:blood* / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism / Q000494:pharmacology*; D050416:Glucagon-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D012709:Serum Albumin / Q000494:pharmacology
D001786:Blood Glucose; D002096:C-Peptide; D012709:Serum Albumin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D001120:Arginine