title: 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?
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 [(18)F]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 be-tween control of food intake and energy balance may contribute to development of obesity in insulin resistance.
authors.affiliation: Medical School Building, King's College London School of Medicine, King's College Hospital Campus, Bessemer Road, London, SE5 9PJ, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Anthony
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Reed
authors.forename: Joel T
authors.initials: JT
authors.lastname: Dunn
authors.forename: Emma
authors.initials: E
authors.lastname: Bingham
authors.forename: David
authors.initials: D
authors.lastname: Hopkins
authors.forename: Paul K
authors.initials: PK
authors.lastname: Marsden
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Amiel
mesh_terms: D000328:Adult; D001066:Appetite / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002149:Energy Intake; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology*; D008875:Middle Aged; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012201:Reward
chemical_list: D007328:Insulin