Immediate Direct Peripheral Vasoconstriction in Response to Hyperinsulinemia and Metformin in the Anesthetized Pig

Abstract

Elevated levels of insulin have been reported to induce both an arterial vasodilation mediated by nitric oxide (NO), and vasoconstriction mediated by endothelin and reactive oxygen radicals. Metformin, used to control blood glucose levels in type 2 diabetes, has also been shown to cause NO-mediated dilation of conduit arteries. It is possible that these contradictory vascular effects are due to a non-direct action on arteries. Therefore, the direct effect of high levels of insulin and metformin infusion on resistance artery diameter was evaluated. Experiments were carried out on the anesthetized pig; blood flow and pressure were measured in the iliac artery. An adjustable snare was applied to the iliac above the pressure and flow measurement site to induce step decreases (3-4 occlusions at 5 min intervals were performed for each infusion) in blood flow, and hence iliac pressure, and the conductance (∆flow / ∆pressure) calculated. Saline, insulin (20 and 40 mUSP/l/min), and metformin (1 µg/ml/min) were infused separately downstream of the adjustable snare and their effect on arterial conductance assessed. Insulin at both infusion rates and metformin caused a significant reduction in peripheral vascular conductance. In conclusion, hyperinsulinemia and metformin infusion constrict resistance arterial vessels in vivo.

Effect of metformin gel against imiquimod–induced psoriasis in mice

“…Both topical and oral metformin exerted a preventive and therapeutic effect. The reduction of erythema may be probably due to the possible vasoconstriction effect of metformin (Markos et al, 2014). Metformin reduced the scaling effect of imiquimod that may be attributed to cell cycle arrest and reduce keratinocyte cell proliferation (Ochoa-Gonzalez et al, 2016).…”

The Regulation of Endothelin-1 in Pregnancies Complicated by Gestational Diabetes: Uncovering the Vascular Effects of Insulin

“…Typically, insulin is thought to increase nitric oxide availability and hence act as a nitric oxide-dependent dilator of resistance vessels. Conversely, elevated levels of insulin can simultaneously induce vasoconstriction mediated by endothelin and reactive oxygen free radicals [38]. Though there is a correlation between insulin resistance and increased ET-1 activity [39], insulin can inhibit ET-1 release from mouse microvascular endothelial cells [40].…”