Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance - The cerebral basis for impaired control of food intake in metabolic syndrome?

K Anthony, L J Reed, J T Dunn, E Bingham, D Hopkins, P K Marsden, S A Amiel

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175 Citations (Scopus)

Abstract

The rising prevalence of obesity and type 2 diabetes is a global challenge. A possible mechanism linking insulin resistance and weight gain would be attenuation of insulin-evoked responses in brain areas relevant to eating in systemic insulin resistance. We measured brain glucose metabolism, using [F-18]fluorodeoxyglucose positron emission tomography, in seven insulin-sensitive (homeostasis model assessment of insulin resistance [HOMA-IR] = 1.3) and seven insulin-resistant (HOMA-IR = 6.3) men, during suppression of endogenous insulin by somatostatin, with and without an insulin infusion that elevated insulin to 24.6 +/- 5.2 and 23.2 +/- 5.8 mU/l (P = 0.76), concentrations similar to fasting levels of the resistant subjects and approximately threefold above those of the insulin-sensitive subjects. Insulin-evoked change in global cerebral metabolic rate for glucose was reduced in insulin resistance (+7 vs. +17.4%, P = 0.033). Insulin was associated with increased metabolism in ventral striatum and prefrontal cortex and with decreased metabolism in right amygdala/hippocampus and cerebellar vermis (P <0.001), relative to global brain. Insulin's effect was less in ventral striatum and prefrontal cortex in the insulin-resistant subjects (mean +/- SD for right ventral striatum 3.2 +/- 3.9 vs. 7.7 1.7, P = 0.017). We conclude that brain insulin resistance exists in peripheral insulin resistance, especially in regions subserving appetite and reward. Diminishing the link between control of food intake and energy balance may contribute to development of obesity in insulin resistance
Original languageEnglish
Pages (from-to)2986 - 2992
Number of pages7
JournalDiabetes
Volume55
Issue number11
DOIs
Publication statusPublished - Nov 2006

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