Effect of Glucagon-Like Peptide 1 (7-36 Amide) on Insulin-Mediated Glucose Uptake in Patients With Type 1 Diabetes
- Graydon S. Meneilly, MD1,
- Christopher H.S. McIntosh, PHD2,
- Raymond A. Pederson, PHD2,
- Joel F. Habener, MD34,
- Mario R.W. Ehlers, PHD5,
- Josephine M. Egan, MD46 and
- Dariush Elahi, PHD4
- 1Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- 2Departement of Physiology, University of British Columbia, Vancouver, British Columbia, Canada
- 3Laboratory of Molecular Endocrinology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts
- 4Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- 5Department of Drug Development, Restoragen, Inc., Lincoln, Nebraska
- 6National Institute on Aging, National Institutes of Health, Baltimore, Maryland
Abstract
OBJECTIVE—To examine the insulinomimetic insulin-independent effects of glucagon-like peptide (GLP)-1 on glucose uptake in type 1 diabetic patients.
RESEARCH DESIGN AND METHODS—We used the hyperinsulinemic-euglycemic clamp (480 pmol · m−2 · min−1) in paired randomized studies of six women and five men with type 1 diabetes. In the course of one of the paired studies, the subjects also received GLP-1 at a dose of 1.5 pmol · kg−1 · min−1. The patients were 41 ± 3 years old with a BMI of 25 ± 1 kg/m2. The mean duration of diabetes was 23 ± 3 years.
RESULTS—Plasma glucose was allowed to fall from a fasting level of ∼11 mmol/l to 5.3 mmol/l in each study and thereafter was held stable at that level. Plasma insulin levels during both studies were ∼900 pmol/l. Plasma C-peptide levels did not change during the studies. In the GLP-1 study, plasma total GLP-1 levels were elevated from the fasting level of 31 ± 3 to 150 ± 17 pmol/l. Plasma glucagon levels fell from the fasting levels of ∼14 pmol/l to 9 pmol/l during both paired studies. Hepatic glucose production was suppressed during the glucose clamps in all studies. Glucose uptake was not different between the two studies (∼40 μmol · kg−1 · min−1).
CONCLUSIONS—GLP-1 does not augment insulin-mediated glucose uptake in lean type 1 diabetic patients.
Footnotes
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Address correspondence and reprint requests to Dariush Elahi, PhD, Massachusetts General Hospital, Geriatric Research Laboratory, GRB SB 0015, 55 Fruit St., Boston, MA 02114. E-mail: delahi{at}partners.org.
Received for publication 28 May 2002 and accepted in revised form 11 November 2002.
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