Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 87, Issue 3, Pages 1282-1290Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.87.3.1282
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Funding
- NCRR NIH HHS [M01RR02719] Funding Source: Medline
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR002719] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [Z01AG000907] Funding Source: NIH RePORTER
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Exendin-4 is a potent and long-acting agonist of the glucagon-like peptide-1 (GLP-1) receptor. GLP-1 is an insulinotropic gut peptide and is being evaluated for the regulation of plasma glucose in type 2 diabetes. The purpose of the present study was to ascertain whether exendin-4 is insulinotropic and whether it has long-lived biological effects in nondiabetic and type 2 diabetic subjects. Because incretins are glucose dependent with respect to their insulin-releasing capacity, we used the hyperglycemic glucose clamp technique to begin to address these issues in two separate protocols. In one protocol, we infused exendin-4 (0.15 pmol.kg(-1).min(-1)) in seven nondiabetic and seven type 2 diabetic subjects during the second hour of a 5-h hyperglycemic clamp in which fasting plasma glucose was raised by 5.4 mmol/liter. The second protocol was identical to the first except that plasma glucose was allowed to fall to the fasting levels during the fourth hour and again raised by 5.4 mmol/liter during the fifth hour in four nondiabetic and four diabetic subjects. With the initiation of exendin-4 infusion at 60 min, plasma insulin response was potentiated 4- to 5-fold in both groups. Despite termination of exendin-4 at the end of the second hour, the insulin levels remained elevated for several hours and hyperglycemia was maintained. All volunteers ate a meal 5.5 h after inducing hyperglycemia. Postprandial plasma glucose, insulin, and GLP-1 did not rise in any subject, possibly because of delayed gastric emptying by exendin-4 even though its infusion had been terminated 4 h previously. We concluded that exendin-4 is a potent and long-lasting insulinotropic agent in nondiabetic and diabetic subjects.
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