Insulin sensitivity is determined by direct effects of circulating insulin on metabolically active tissues in combination with indirect effects of circulating insulin, i.e. via the central nervous system. The dose-response effects of insulin differ between the various physiological effects of insulin. At lower insulin concentrations, circulating insulin inhibits endogenous glucose production through a combination of direct and indirect effects. At higher insulin concentrations, circulating insulin also stimulates glucose uptake and fatty acid uptake in adipose tissue, again through direct and indirect effects. High-fat diet induces insulin resistance in the central nervous system, which contributes considerably to overall insulin resistance of liver and peripheral tissues. Central insulin resistance is amendable to therapeutic intervention, reflected in the central effects of topiramate and glucagon-like peptide-1 on hepatic and peripheral insulin resistance in insulin resistant mice.
© 2014 S. Karger AG, Basel.