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(Hypertension. 2000;36:239.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Effects of Angiotensin-Converting Enzyme Inhibitors on Glucose Uptake

Akira Kudoh; Akitomo Matsuki

From the Department of Anesthesiology, University of Hirosaki School of Medicine, Aomori, Japan.

Correspondence to Akira Kudoh, MD, 5 Zaifucho, Hirosaki 036, Aomori, Japan.

Abstract—We investigated the effect of angiotensin-converting enzyme inhibitors on glucose uptake regulation as well as the effect of bradykinin (BK) on glucose uptake and its regulation by using inhibitors of phospholipase C, BK B2 receptor, protein kinase C, phosphatidylinositol 3-kinase, tyrosine kinase, and intracellular Ca²⁺. We measured 2-deoxyglucose uptake by using L₆ skeletal muscle cells. In the presence of 1 nmol/L of insulin, 1 µmol/L of enalaprilat enhanced insulin-induced glucose uptake from 89.2±8.1 to 138.0±13.6 pmol/h per mg protein. The stimulation of glucose uptake with enalaprilat was blocked to 92.7±7.8 pmol/h per mg protein by 10 µmol/L HOE 140 (a BK B2 receptor antagonist). In the presence of 1 nmol/L of insulin, exposure to 10 µmol/L BK stimulated glucose uptake from 89.2±8.1 to 171.6±10.1 pmol/h per mg protein. However, in the absence of insulin, BK could not enhance glucose uptake. One hundred nanomoles per liter of tyrphostin A-23 and genistein, which are tyrosine kinase inhibitors, significantly decreased the BK-induced glucose uptake from 142.0±8.4 to 87.6±6.4 and 85.2±7.3 pmol/h per mg protein, respectively. BK-induced glucose uptake was inhibited significantly by 10 µmol/L U73122 (a phospholipase C antagonist) from 142.0±8.4 to 95.7±9.5 pmol/h per mg protein. One and 20 µmol/L of TMB-8 (an intracellular calcium antagonist) significantly decreased BK-induced glucose uptake from 142.0±8.4 to 108.0±9.6 and 100.8±11.4 pmol/h per mg protein. Angiotensin-converting enzyme inhibitors enhanced insulin-induced glucose uptake via the BK B2 receptor. BK-stimulated glucose uptake is related to phospholipase C, tyrosine kinase, and an increase in intracellular calcium.

Key Words: angiotensin-converting enzyme inhibitors • bradykinin • glucose • calcium • phospholipases • protein kinases

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