Effects of metformin on tyrosine kinase activity, glucose transport, and intracellular calcium in rat vascular smooth muscle
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-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.
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In ex-vivo preparations of vascular smooth muscle, a direct vasodilating action of metformin has been reported, possibly due to altered calcium handling.
“Also, in ex-vivo preparations of vascular smooth muscle, a direct vasodilating action of metformin has been reported, possibly due to altered calcium handling (35,37,38).”
From Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus (2001) · cites this paper as [38]
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- Authors
- Dominguez, L. J., Davidoff, A. J., Srinivas, P. R., Standley, P. R., Walsh, M. F., & Sowers, J. R.
- Affiliations
- Wayne State University (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1996-01
- Volume
- 137
- Issue
- 1
- Pages
- 113-121
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1991165701
- Cited by
- 87
- References
- 0
- Citations by year
- 2025: 2 · 2024: 2 · 2022: 1 · 2020: 1 · 2018: 2 · 2017: 3 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 5
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- metformin, tyrosine kinase activity, insulin receptor, IGF-1 receptor, glucose transport, intracellular calcium, vascular smooth muscle cells, aorta, insulin action, antihypertensive effect
- MeSH terms
- Animals, Biological Transport, Calcium, Cells, Cultured, Glucose, Insulin, Insulin-Like Growth Factor I, Intracellular Membranes, Male, Metformin, Muscle, Smooth, Vascular, Osmolar Concentration, Protein-Tyrosine Kinases, Rats, Sprague-Dawley, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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