Effects of metformin on tyrosine kinase activity, glucose transport, and intracellular calcium in rat vascular smooth muscle

Ligia J. Dominguez, Amy J. Davidoff, Pothur R. Srinivas, Paul R. Standley, Mary F. Walsh, James R. Sowers

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Metformin enhances peripheral insulin action and reduces blood pressure in hypertensive rats. Our group has previously reported that insulin and insulin-like growth factor I (IGF-I) attenuate both agonist-induced vascular smooth muscle cell (VSMC) contraction and associated increases in cytosolic free calcium ([Ca](i)). Thus, changes in insulin actions may explain in part metformin's vascular effects. However, metformin's mechanism of action at the vasculature had not been elucidated. Therefore, the purpose of this study was to determine whether metformin evokes alterations in VSMC insulin and IGF-I receptors, glucose transport, and/or [Ca](i). We quantitated hormone binding and tyrosine kinase (TK) activity in partially purified insulin and IGF-I receptors prepared from metformin-treated (100 μm) and control rat aortic VSMC in culture. Glucose transport was assessed by 2-deoxyglucose uptake. Metformin exposure for 24 h 1) increased basal TK activity (metformin, 3.49 ± 0.39; control, 1.77 ± 0.39 pmol 32P incorporated/mg protein; P < 0.01) without changes in insulin- or IGF-I-stimulated TK activity, 2) increased 2- deoxyglucose transport in a dose-dependent manner, 3) decreased insulin (P < 0.01) and IGF-I binding (P < 0.05), and 4) decreased thrombin-induced elevation in [Ca](i) (metformin, 10.3%; control, 35.3% over basal; P < 0.05). These insulin/IGF-I-like effects of metformin may help explain some of its vascular actions.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalEndocrinology
Volume137
Issue number1
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Endocrinology

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