To determine the effect of tolbutamide on insulin release to nonglucose stimuli in non-insulin-dependent diabetes mellitus and how plasma glucose levels may modulate this effect, the acute insulin response (AIR) to an isoproterenol (12 μg) or an arginine (5 g) i.v. pulse was determined before and during a tolbutamide infusion (7.5 mg/m2/min) in 25 male subjects. During the tolbutamide infusion, there was an increase in the AIR to both isoproterenol (% Δ AIR = +49 ± 21%, N = 11, P < 0.05) and arginine (% Δ AIR = +52 ± 15%, N = 12, P < 0.005) and a decrease in plasma glucose (Δ plasma glucose for isoproterenol = −24 ± 6 mg/dl, P < 0.005; for arginine = −26 ± 3 mg/dl, P < 0.001). In separate studies, when the plasma glucose was clamped at baseline values by a variable rate of glucose infusion, there was a greater effect of tolbutamide on AIR when compared with the unclamped tolbutamide studies (isoproterenol: % Δ AIR = +132 ± 25%, P < 0.025; arginine: % Δ AIR = +95 ± 12%, P < 0.05). Thus, tolbutamide increases the AIR of nonglucose stimuli, but this augmentation by tolbutamide is blunted by the concomitant decrease in plasma glucose. Consideration of this observation is necessary when interpretating the effects of a sulfonylurea on islet cell responses.
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Original Contributions|
February 01 1982
Insulin Responses to Nonglucose Stimuli in Non-insulin-dependent Diabetes Mellitus During a Tolbutamide Infusion
Michael A Pfeifer;
Michael A Pfeifer
Department of Medicine, University of Washington School of Medicine, Division of Endocrinology and Metabolism, and the Geriatric Research, Education, and Clinical Center at the Veterans Administration Medical Center
Seattle, Washington
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Jeffrey B Halter;
Jeffrey B Halter
Department of Medicine, University of Washington School of Medicine, Division of Endocrinology and Metabolism, and the Geriatric Research, Education, and Clinical Center at the Veterans Administration Medical Center
Seattle, Washington
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James C Beard;
James C Beard
Department of Medicine, University of Washington School of Medicine, Division of Endocrinology and Metabolism, and the Geriatric Research, Education, and Clinical Center at the Veterans Administration Medical Center
Seattle, Washington
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Roman Judzewitsch;
Roman Judzewitsch
Department of Medicine, University of Washington School of Medicine, Division of Endocrinology and Metabolism, and the Geriatric Research, Education, and Clinical Center at the Veterans Administration Medical Center
Seattle, Washington
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Daniel Porte, Jr
Daniel Porte, Jr
Department of Medicine, University of Washington School of Medicine, Division of Endocrinology and Metabolism, and the Geriatric Research, Education, and Clinical Center at the Veterans Administration Medical Center
Seattle, Washington
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Address reprint requests to Michael A. Pfeifer, M.D., Medical Research Service (151), VA Medical Center, 800 Zorn Avenue, Louisville, Kentucky 40202.
Diabetes 1982;31(2):154–159
Article history
Received:
May 18 1981
Revision Received:
October 06 1981
Accepted:
October 06 1981
PubMed:
6759232
Citation
Michael A Pfeifer, Jeffrey B Halter, James C Beard, Roman Judzewitsch, Daniel Porte; Insulin Responses to Nonglucose Stimuli in Non-insulin-dependent Diabetes Mellitus During a Tolbutamide Infusion. Diabetes 1 February 1982; 31 (2): 154–159. https://doi.org/10.2337/diab.31.2.154
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