Effects of glucagon-like peptide-1 on islet function and insulin sensitivity in noninsulin-dependent diabetes mellitus.
Administration of the truncated glucagon-like peptide 1 (GLP-1) has been considered for treatment of noninsulin-dependent diabetes mellitus (NIDDM). We studied its antidiabetogenic mechanism by examining its influences on islet function and peripheral insulin sensitivity in six subjects (aged 56-74 yr) with well-controlled NIDDM. Islet function was evaluated with arginine stimulation at three plasma glucose levels (fasting, 14 mmol/L, and > 28 mmol/L). GLP-1 (1.5 pmol/kg per min iv) increased serum insulin levels at fasting glucose (P = 0.028), at 14 mmol/L glucose (P = 0.028), and at 28 mmol/L glucose (P = 0.028). The acute insulin response (AIR) to 5 g iv arginine was increased by GLP-1 at 14 mmol/L glucose (P = 0.028), and the slopeAIR, i.e., the glucose potentiation of insulin secretion, was markedly increased by GLP-1 (P = 0.028). Plasma glucagon levels were reduced by GLP-1 (P = 0.028), and arginine-stimulated glucagon secretion (AGR) was inhibited by GLP-1 at 14 (P = 0.046) and 28 mmol/L glucose (P = 0.028). Glucose-induced inhibition of arginine-stimulated glucagon secretion (slopeAGR) was not significantly affected by GLP-1. In contrast, GLP-1 did not affect the low insulin sensitivity during a hyperinsulinemic, euglycemic clamp. Thus, GLP-1 improves islet dysfunction in diabetes, mainly by increasing the glucose-induced potentiation of insulin secretion. In contrast, the peptide does not seem to improve insulin resistance in NIDDM.
Ahrén
B
B
Department of Medicine, Lund University, Malmö, Sweden.
Larsson
H
H
Holst
J J
JJ
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood / Q000627:therapeutic use*
D007328:Insulin; D010455:Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon