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(Circulation. 1995;92:1597-1603.)
© 1995 American Heart Association, Inc.

Articles

Insulin-Stimulated Glucose Transport Inhibits Ca²⁺ Influx and Contraction in Vascular Smooth Muscle

Andrew M. Kahn, MD; Richard A. Lichtenberg, MD; Julius C. Allen, PhD; Charles L. Seidel, PhD; Tom Song, BS

From the Departments of Medicine, University of Texas Medical School, Houston (A.M.K., T.S.); Baylor College of Medicine, Houston (J.C.A., C.L.S.); and Mercy Haverford Hospital, Havertown, Pa (R.A.L.).

Correspondence to Andrew M. Kahn, MD, University of Texas Medical School, PO Box 20708, MSB 4.138, Houston, TX 77025.

Background Insulin attenuates serotonin-induced Ca²⁺ influx, the intracellular Ca²⁺ transient, and contraction of cultured vascular smooth muscle cells from dog femoral artery. These studies were designed to test whether insulin-induced glucose transport was an early event leading to the inhibitory effects of insulin on Ca²⁺ influx, intracellular Ca²⁺ concentration, and contraction in these cells.

Methods and Results Insulin 1 nmol/L stimulated the 30-minute uptake of [³H]2-deoxyglucose in these cells via a phloridzin-inhibitable mechanism. Contraction of individual cells was measured by photomicroscopy, intracellular Ca²⁺ concentration was monitored by measuring fura 2 fluorescence by use of Ca²⁺-sensitive excitation wavelengths, and Ca²⁺ influx was estimated by the rate of Mn²⁺ quenching of intracellular fura 2 fluorescence when excited at a Ca²⁺-insensitive wavelength. In the presence of 5 mmol/L glucose, preincubation of cells for 30 minutes with 1 nmol/L insulin inhibited 10^-5 mol/L serotonin-induced contraction of individual cells by 62% (P<.01) and decreased the serotonin-stimulated component of Mn²⁺ influx by 78% (P<.05). Removing glucose from the preincubation medium or adding 1 mmol/L phloridzin completely eliminated these effects of insulin. Insulin lowered the serotonin-induced intracellular Ca²⁺ peak by 37% (P<.05), and phloridzin blocked this effect of insulin. When glucose uptake was increased to the insulin-stimulated level by preincubation of the cells for 30 minutes with 25 mmol/L glucose in the absence of insulin, serotonin failed to stimulate Mn²⁺ influx, the serotonin-induced Ca²⁺ peak was decreased by 46% (P<.05), serotonin-induced contraction was inhibited by 60% (P<.01), and addition of insulin did not further inhibit contraction.

Conclusions Since the effects of insulin on serotonin-stimulated Ca²⁺ transport, intracellular Ca²⁺ concentration, and contraction were dependent on glucose transport and were duplicated when glucose transport was stimulated by high extracellular glucose concentration rather than insulin per se, it is concluded that insulin-stimulated glucose transport is an early event that leads to decreased Ca²⁺ influx and contraction in vascular smooth muscle.

Key Words: manganese • hypertension • insulin • fura 2

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