Hyperinsulinemia in preascitic cirrhosis: Effects on systemic and renal hemodynamics, sodium homeostasis, forearm blood flow, and sympathetic nervous activity
Authors: F WONG
Journal: Hepatology (1996)

no further renal vasodilatation except at very high phar-Insulin has been shown to be vasodilatory and antinamacological levels of insulin together with an untriuretic and to stimulate sympathetic nervous activity changed GFR, natriuresis, and diuresis.Hyperinsulinindependent of hypoglycemia in healthy normal subemia produced no significant effects on the sympathetic jects.It is hypothesized that hyperinsulinemia, which is nervous activity.In conclusion, these results suggest commonly observed in cirrhosis, may in part be responthat hyperinsulinemia may be implicated in the glomersible for the systemic vasodilatation, sympathetic activaular hyperfiltration and sodium retaining tendency of tion, and sodium retention in these patients.The aims preascitic cirrhotic patients with glucose intolerance. of this study, in preascitic cirrhotics, were as follows: (1)The ability of the kidneys to escape from the sodium to document baseline hyperinsulinemia and its effects retaining effects may serve as an in-built physiological on sodium handling, forearm and renal circulations, and regulatory mechanism on sodium homeostasis.(HEPAsympathetic nervous activity; (2) to determine if phar-TOLOGY 1996;23:414-422.)macological increases in plasma insulin levels would result in an exaggeration of these physiological effects.Seven male, nonobese, well-compensated, preascitic cir-Hyperinsulinemia 1 and insulin resistance are wellrhotic patients were studied, after being maintained on described features 2 of cirrhosis, often leading to glucose a 150 mmol sodium per day diet for 7 days, firstly at intolerance. [3]4][5] Apart from its effects on carbohydrate baseline level, followed by increasing doses of insulin metabolism, insulin has multiple other physiological from 10 to 1,200 mU/m 2 /min using the euglycemic clamp actions.In healthy normal subjects, insulin has been technique.Systemic and renal hemodynamics, urinary shown to be both vasodilatory 6-8 and antinatriuretic. 9-12sodium excretion, plasma norepinephrine, and forearm The vasodilatory effect of insulin is mainly on the skeleblood flow (FBF) were measured at the end of baseline tal circulation, leading to an increase in skeletal blood and each hyperinsulinemic period.Baseline measureflow and a decrease in skeletal vascular resistance ments in the cirrhotics, when compared with our laboratory standards obtained from a comparable group of without affecting the systemic circulation. 13The effects male healthy normals, showed significant hyperinsulinon the renal circulation are less well documented, alemia (P Å .01),associated with significantly higher FBF though recent literature suggests that insulin also in-(P Å .02),and glomerular filtration rate (GFR) (P Å .02),creases renal plasma flow. 10,14The antinatriuretic efas well as significantly reduced urinary volume (P fect of insulin is thought to be caused by either a direct Å .04)and fractional excretion of sodium (P Å .04).Insutubular action 9,10 or indirectly via sympathetic activalin infusions in the cirrhotics produced no further sotion. 15Indeed, the increased sodium retention associdium retention, but further forearm vasodilatation ocated with hyperinsulinemia has been implicated in the curred at doses ¢ 10 mU/m 2 /min.In contrast, there was pathogenesis of essential hypertension 16,17 and the volume expansion observed in diabetes. 18 The effect of insulin on the sympathetic nervous system is contro-