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

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-1) attenuate both agonist-induced vascular smooth muscle cell (VSMC) contraction and associated increases in cytosolic fr...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 1996-01, Vol.137 (1), p.113-121
Main Authors: Dominguez, L J, Davidoff, A J, Srinivas, P R, Standley, P R, Walsh, M F, Sowers, J R
Format: Article
Language:English
Subjects:
Aorta
Blood pressure
Calcium
Calcium (blood)
Calcium (intracellular)
Calcium transport
Cell culture
Deoxyglucose
Glucose
Glucose transport
Growth factors
Insulin
Insulin-like growth factor I
Insulin-like growth factor I receptors
Insulin-like growth factors
Kinases
Metformin
Muscle contraction
Muscles
Pressure effects
Protein-tyrosine kinase
Receptors
Smooth muscle
Thrombin
Tyrosine
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Summary: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-1) 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 microM) 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 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.
ISSN:0013-7227
1945-7170
DOI:10.1210/endo.137.1.8536601