Evaluation of beta-cell secretory capacity using glucagon-like peptide 1.

OBJECTIVE: Beta-cell secretory capacity is often evaluated with a glucagon test or a meal test. However, glucagon-like peptide 1 (GLP-1) is the most insulinotropic hormone known, and the effect is preserved in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We first compared the effects of intravenous bolus injections of 2.5, 5, 15, and 25 nmol GLP-1 with glucagon (1 mg intravenous) and a standard meal (566 kcal) in 6 type 2 diabetic patients and 6 matched control subjects. Next, we studied another 6 patients and 6 control subjects and, in addition to the above procedure, performed a combined glucose plus GLP-1 stimulation, where plasma glucose was increased to 15 mmol/l before injection of 2.5 nmol GLP-1. Finally, we compared the insulin response to glucose plus GLP-1 stimulation with that observed during a hyperglycemic arginine clamp (30 mmol/l) in 8 patients and 8 control subjects.
RESULTS: Peak insulin and C-peptide concentrations were similar after the meal, after 2.5 nmol GLP-1, and after glucagon. Side effects were less with GLP-1 than with glucagon. Peak insulin and C-peptide concentrations were as follows (C-peptide concentrations are given in parentheses): for patients (n = 12): meal, 277 +/- 42 pmol/l (2,181 +/- 261 pmol/l); GLP-1 (2.5 nmol), 390 +/- 74 pmol/l (2,144 +/- 254 pmol/l); glucagon, 329 +/- 50 pmol/l (1,780 +/- 160 pmol/l); glucose plus GLP-1, 465 +/- 87 pmol/l (2,384 +/- 299 pmol/l); for control subjects (n = 12): meal, 543 +/- 89 pmol/l (2,873 +/- 210 pmol/l); GLP-1, 356 +/- 51 pmol/l (2,001 +/- 130 pmol/l); glucagon, 420 +/- 61 pmol/l (1,995 +/- 99 pmol/l); glucose plus GLP-1, 1,412 +/- 187 pmol/l (4,391 +/- 416 pmol/l). Peak insulin and C-peptide concentrations during the hyperglycemic arginine clamp and during glucose plus GLP-1 injection were as follows: for patients: 475 +/- 141 pmol/l (2,295 +/- 379 pmol/l) and 816 +/- 268 pmol/l (3,043 +/- 508 pmol/l), respectively; for control subjects: 1,403 +/- 308 pmol/l (4,053 +/- 533 pmol/l) and 2,384 +/- 452 pmol/l (6,047 +/- 652 pmol/l), respectively.
CONCLUSIONS: GLP-1 (2.5 nmol = 9 microg) elicits similar secretory responses to 1 mg glucagon (but has fewer side effects) and a standard meal. Additional elevation of plasma glucose to 15 mmol/l did not enhance the response further. The incremental response was similar to that elicited by arginine, but hyperglycemia had an additional effect on the response to arginine.