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*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*EPINEPHRINE
*GLUCAGON
*TOLBUTAMIDE
Medline Plus Health Information
*Hypoglycemia
The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 5 1458-1461
Copyright © 1997 by The Endocrine Society

Clinical Studies

The Use of Tolbutamide-Induced Hypoglycemia to Examine the Intraislet Role of Insulin in Mediating Glucagon Release in Normal Humans1

Steven R. Peacey, Amin Rostami-Hodjegan, Emad George, Geoffrey T. Tucker and Simon R. Heller

University Department of Medicine (S.R.P., E.G.), Clinical Sciences Centre and Diabetes Centre (S.R.H.), Northern General Hospital, Sheffield, United Kingdom, S5 7AU; and Department of Pharmacology and Therapeutics (A.R.H., G.T.T.), Royal Hallamshire Hospital, Sheffield, United Kingdom, S10 2JF

Address all correspondence and requests for reprints to: Dr. Steven R. Peacey, Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, United Kingdom.

Disruption of intraislet mechanisms could account for the impaired glucagon response to hypoglycemia in type 1 diabetes. However, in contrast to animals, there is conflicting evidence that such mechanisms operate in humans. We have used iv tolbutamide (T) (1.7 g bolus + 130 mg/h infusion) to create high portal insulin concentrations and compared this with equivalent hypoglycemia using an iv insulin infusion (I) (30 mU/m2·min). Ten normal subjects underwent two hypoglycemic clamps; mean glucose; I (53 ± 1 mg/dL); and T (53 ± 1 mg/dL) (2.9 ± 0.04 mmol/L vs. 2.9 ± 0.05 mmol/L), held for 30 min. During hypoglycemia, mean peripheral insulin levels were greater with I (59 ± 4 mU/L) than T (18 ± 3 mU/L), P < 0.001. Calculated peak portal insulin concentrations were greater during T (282 ± 28 mU/L) than I (78 ± 4 mU/L), P < 0.00005. The demonstration of a reduced glucagon response during T-induced hypoglycemia (111 ± 8 ng/L vs. 135 ± 12 ng/L, P < 0.05) with higher portal insulin concentrations suggests that intraislet mechanisms may contribute to the release of glucagon during hypoglycemia in man.




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