Disparate effects of insulin on isolated rabbit afferent and efferent arterioles.

Abstract

Despite evidence that insulin per se may be an important regulator of glomerular hemodynamics, little is known about its direct action on the glomerular afferent arterioles (Af-Art) and efferent arterioles (Ef-Art), the crucial vascular segments that control glomerular hemodynamics. In the present study, we examined the direct effect of physiological concentrations of insulin on isolated microperfused rabbit Af-and Ef-Arts. After cannulation, vessels were equilibrated in insulin-free medium for 30 min. To determine whether insulin causes vasodilation or constriction, increasing doses (5, 20, and 200 ,U/ml) were added to the bath and lumen of arterioles that were either preconstricted to 50% of control diameter with norepinephrine or left nonpreconstricted. Insulin caused no vasoconstriction in either Af-or Ef-Arts, but it reversed norepinephrine-induced constriction in Ef-Arts but not Af-Arts (suggesting a vasodilator action selective to the Ef-Art): at 200 MU/ml, insulin increased Ef-Art luminal diameter by 75.8±7.0% from the preconstricted level (n = 6; P < 0.008). The vasorelaxant effect of insulin on Ef-Arts was not affected by blockade of either endotheliumderived relaxing factor/nitric oxide or prostaglandin synthesis. Despite the lack of effect of insulin on Af-Art when added after the equilibration period, when Af-Arts were equilibrated in the presence of either 20 or 200 MU/ml insulin, their basal diameter was significantly reduced (11.7±0.9 ,m; P < 0.025, n = 6, and 12.0±0.9 Mm; P < 0.025, n = 7, respectively) compared with nontreated Af-Arts (16.2±1.3 Am; n = 7). In conclusion, this study demonstrates that at physiological concentrations, insulin dilates NE-constricted Ef-Arts, while insulin pretreatment enhances Af-Art tone. The disparate actions of insulin on the Af-vs the Ef-Art may contribute to its beneficial effect on glomerular hypertension. (J. Clin. Inwest. 1993. 92:1981

Sex-specific action of insulin to acutely increase the metabolic clearance rate of dehydroepiandrosterone in humans.

“…Hence, the study's findings support the idea that insulin acts as a physiologic regulator of DHEA metabolism in men (7). A theoretical mechanism by which insulin could increase the MCRDHEA in men might involve insulin's well-described vasodilatory action (40)(41)(42)(43). By acting as a vasodilator, insulin would acutely enhance delivery of DHEA to fat depots, where this lipophilic steroid could accumulate.…”

Factors Affecting Progression of Renal Failure in Patients With Type 2 Diabetes

“…Our results suggest that renal clearance of insulin may be reduced in patients without insulin therapy, resulting in a decreased requirement for insulin therapy, i.e., patients without insulin therapy had a greater decrease in capacity of insulin clearance caused by more advanced deterioration of renal function, making this a significant predictor of poor renal prognosis. Several clinical and experimental studies have demonstrated that insulin mediates vasodilation in various vascular beds, including the renal vasculature (21)(22)(23)(24). In patients receiving insulin therapy in the present study, insulin may have had a vasodilatory effect and therefore a renoprotective effect.…”

Glomerular Diseases

“…There tends to be less diffuse foot process effacement on electron microscopy than that seen in patients with primary FSGS (30)(31)(32). Risk factors identified by physiological studies that may contribute to the development of the lesion include elevations of renal plasma flow and GFR, insulin resistance leading to an increased transcapillary pressure gradient and increased synthesis of growth factors promoting glomerular hypertrophy (33,34). Elevated plasma levels of leptin through upregulation of TGF-b1 in obesity may also predispose to glomerulosclerosis (35).…”