Peripheral glucose homeostasis: does brain insulin matter?
Barry E. Levin, Robert S. Sherwin
Barry E. Levin, Robert S. Sherwin
Published August 25, 2011
Citation Information: J Clin Invest. 2011;121(9):3392-3395. https://doi.org/10.1172/JCI59653.
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Commentary

Peripheral glucose homeostasis: does brain insulin matter?

Abstract

Much controversy surrounds the relative role of insulin signaling in the brain in the control of hepatic glucose metabolism. In this issue of the JCI, Ramnanan and colleagues demonstrate that arterial infusion of insulin into the brains of dogs reduces net hepatic glucose output without altering endogenous glucose production. However, this effect was modest and required both prolonged fasting and prolonged exposure of the brain to insulin, raising doubts about the overall physiological relevance of insulin action in the brain on hepatic glucose metabolism. Given the dominant direct role that insulin plays in inhibiting glucose production in the liver, we suggest that the main effect of central insulin on hepatic glucose metabolism may be more chronic and assume greater significance either when portal insulin is deficient, as occurs during exogenous insulin treatment of type 1 diabetes, or when chronic hyperinsulinemia and central insulin resistance develops, as occurs in type 2 diabetes.

Authors

Barry E. Levin, Robert S. Sherwin

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Figure 1

Effect of insulin delivery to the brain on hepatic glucose metabolism in the rat (3) and dog (5).

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Effect of insulin delivery to the brain on hepatic glucose metabolism in...
In the rat, insulin was administered i.c.v. in supraphysiological doses, whereas in the dog, insulin was administered via direct carotid and vertebral arterial infusion, which raised levels to the upper physiological range. In both cases, plasma glucose was kept at baseline using variable glucose infusion and somatostatin to suppress endogenous insulin and glucagon secretion. However, in the rat, insulin alone was replaced systemically, whereas in the dog, both insulin and glucagon were directly delivered to the liver to maintain portal levels. In both models, changes in hepatic glucose metabolism were observed: in the rat, HGP was inhibited; in the dog, a change in HGP was not seen, but hepatic glucose uptake (HGU) increased, thereby diminishing NHGO.