Insulin action in the brain regulates both central and peripheral functions

Rahul Agrawal, Candace M. Reno, Sunny Sharma, Camille Christensen, Yiqing Huang, Simon J. Fisher

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

Abstract

The brain has been traditionally thought to be insensitive to insulin, primarily because insulin does not stimulate glucose uptake/metabolism in the brain (as it does in classic insulin-sensitive tissues such as muscle, liver, and fat). However, over the past 20 years, research in this field has identified unique actions of insulin in the brain. There is accumulating evidence that insulin crosses into the brain and regulates central nervous system functions such as feeding, depression, and cognitive behavior. In addition, insulin acts in the brain to regulate systemic functions such as hepatic glucose production, lipolysis, lipogenesis, reproductive competence, and the sympathoadrenal response to hypoglycemia. Decrements in brain insulin action (or brain insulin resistance) can be observed in obesity, type 2 diabetes (T2DM), aging, and Alzheimer’s disease (AD), indicating a possible link between metabolic and cognitive health. Here, we describe recent findings on the pleiotropic actions of insulin in the brain and highlight the precise sites, specific neuronal population, and roles for supportive astrocytic cells through which insulin acts in the brain. In addition, we also discuss how boosting brain insulin action could be a therapeutic option for people at an increased risk of developing metabolic and cognitive diseases such as AD and T2DM. Overall, this perspective article serves to highlight some of these key scientific findings, identify unresolved issues, and indicate future directions of research in this field that would serve to improve the lives of people with metabolic and cognitive dysfunctions.

Original languageEnglish
Pages (from-to)156-163
Number of pages8
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume321
Issue number1
DOIs
StatePublished - Jul 2021

Bibliographical note

Funding Information:
This work was supported by funding from the National Institutes of Health Grants NS070235 and DK118082 (to S.J.F), by Juvenile Diabetes Research Foundation Grant 1-FAC-2020-984-A-N (to C.M.R.), and by the University of Utah’s Diabetes and Metabolism Research Center.

Funding Information:
This work was supported by funding from the National Institutes of Health Grants NS070235 and DK118082 (to S.J.F), by Juvenile Diabetes Research Foundation Grant 1-FAC-2020-984-A-N (to C.M.R.), and by the University of Utah?s Diabetes and Metabolism Research Center.

Publisher Copyright:
Copyright © 2021 the American Physiological Society.

Keywords

  • Brain
  • Diabetes
  • Hypoglycemia
  • Hypothalamus
  • Insulin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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