Glucagon-like peptide-1 augments insulin-mediated glucose uptake in the obese state.
The insulinotropic hormone, glucagon-like peptide-1 (GLP-1), is being examined as a potential new agent for treatment in type 2 diabetic patients. Whereas the insulinotropic properties of this peptide are well established, another property of the hormone, an insulinomimetic effect per se, is controversial. In the normal glucose-tolerant lean state, it is difficult to demonstrate an insulinomimetic effect. The current study was conducted to examine whether GLP-1 has insulinomimetic effect in the obese state. Ten obese volunteers (body mass index, 34.6 +/- 0.8 kg/m(2)), whose ages were 32.5 +/- 3.0 yr, participated in two euglycemic clamp studies (n = 20 clamps) for 120 min. Five of the volunteers were females. The initial clamp was performed with a primed (0-10)-constant (10-60) infusion of GLP-1 at a final rate of 1.5 pmol x kg(-1) x min(-1). At 60 min, the GLP-1 infusion was terminated, and euglycemic was maintained from 60-120 min. After the GLP-1 study, each individual's plasma insulin level was measured. A second study was performed that was identical to the first, with the infusion of regular insulin in place of GLP-1. Insulin infusion rates were regulated in each individual to simulate plasma insulin levels produced during the GLP-1 infusion. The rate of disappearance of glucose was calculated for each subject. Fasting plasma insulin levels were similar between studies. In response to the GLP-1 infusion, with maintenance of plasma glucose level clamped at fasting level, significant increases in plasma insulin occurred in all subjects (P < 0.001). The insulin levels during the insulin infusion study were similar to that induced by GLP-1. The rate of disappearance of glucose (insulin-mediated glucose uptake) progressively increased in response to both the GLP-1 and insulin infusion. However, the rate of disappearance of glucose during the GLP-1 study was significantly higher (P = 0.033) than during the insulin study. We conclude that in insulin-resistant states, GLP-1 has insulinomimetic properties per se.
Egan
Josephine M
JM
Diabetes Section, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Meneilly
Graydon S
GS
Habener
Joel F
JF
Elahi
Dariush
D
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D004359:Drug Therapy, Combination; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000008:administration & dosage* / Q000097:blood; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000493:pharmacokinetics; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage*; D011498:Protein Precursors / Q000008:administration & dosage*
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose