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Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

Kleinridders, André, Ferris, Heather A., Cai, Weikang, Kahn, C. Ronald·2014·Diabetes
DOI 10.2337/db14-0568
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Abstract

Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases.

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  • The increase in Angptl4 in the hypothalamus of ob/ob type 2 diabetic mice is most likely due to insulin resistance.

    “The increase in Angplt4 in type 2 diabetes in hypothalamus of ob/ob mice is most likely due to insulin resistance, since we [37,38] and others [39,40] have shown, obesity is associated with increased inflammation and mitochondrial dysfunction at the level of the hypothalamus and both of these can contribute to an altered insulin response.”

    From Differential effects of angiopoietin-like 4 in brain and muscle on regulation of lipoprotein lipase activity (2015) · cites this paper as [37]

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Metadata

Authors
Kleinridders, A., Ferris, H. A., Cai, W., & Kahn, C. R.
Affiliations
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA
Venue
Diabetes
Publisher
American Diabetes Association
Published
2014-06-14
Volume
63
Issue
7
Pages
2232-2243
ISSN
  • 0012-1797
  • 1939-327X
DOI
10.2337/db14-0568
Cited by
625
References
22
Language
en

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