Effect of endogenous GLP-1 on insulin secretion in type 2 diabetes.
OBJECTIVE
The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) account for up to 60% of postprandial insulin release in healthy people. Previous studies showed a reduced incretin effect in patients with type 2 diabetes but a robust response to exogenous GLP-1. The primary goal of this study was to determine whether endogenous GLP-1 regulates insulin secretion in type 2 diabetes.


METHODS
Twelve patients with well-controlled type 2 diabetes and eight matched nondiabetic subjects consumed a breakfast meal containing D-xylose during fixed hyperglycemia at 5 mmol/l above fasting levels. Studies were repeated, once with infusion of the GLP-1 receptor antagonist, exendin-(9-39) (Ex-9), and once with saline.


RESULTS
The relative increase in insulin secretion after meal ingestion was comparable in diabetic and nondiabetic groups (44 +/- 4% vs. 47 +/- 7%). Blocking the action of GLP-1 suppressed postprandial insulin secretion similarly in the diabetic and nondiabetic subjects (25 +/- 4% vs. 27 +/- 8%). However, Ex-9 also reduced the insulin response to intravenous glucose (25 +/- 5% vs. 26 +/- 7%; diabetic vs. nondiabetic subjects), when plasma GLP-1 levels were undetectable. The appearance of postprandial ingested d-xylose in the blood was not affected by Ex-9.


CONCLUSIONS
These findings indicate that in patients with well-controlled diabetes, the relative effects of enteral stimuli and endogenous GLP-1 to enhance insulin release are retained and comparable with those in nondiabetic subjects. Surprisingly, GLP-1 receptor signaling promotes glucose-stimulated insulin secretion independent of the mode of glucose entry. Based on rates of D-xylose absorption, GLP-1 receptor blockade did not affect gastric emptying of a solid meal.
Salehi
Marzieh
M
University of Cincinnati, Department of Internal Medicine, Cincinnati, Ohio, USA. salehim@uc.edu
Aulinger
Benedict
B
Prigeon
Ronald L
RL
D'Alessio
David A
DA
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004040:Dietary Carbohydrates; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D012016:Reference Values; D014994:Xylose / Q000097:blood
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D014994:Xylose; D005947:Glucose