Title

Central Nervous System Control of Glucose Homeostasis: A Therapeutic Target for Type 2 Diabetes?

Document Type

Article

Abstract

Historically, pancreatic islet beta cells have been viewed as principal regulators of glycemia, with type 2 diabetes (T2D) resulting when insulin secretion fails to compensate for peripheral tissue insulin resistance. However, glycemia is also regulated by insulin-independent mechanisms that are dysregulated in T2D. Based on evidence supporting its role both in adaptive coupling of insulin secretion to changes in insulin sensitivity and in the regulation of insulin-independent glucose disposal, the central nervous system (CNS) has emerged as a fundamental player in glucose homeostasis. Here, we review and expand upon an integrative model wherein the CNS, together with the islet, establishes and maintains the defended level of glycemia. We discuss the implications of this model for understanding both normal glucose homeostasis and T2D pathogenesis and highlight centrally targeted therapeutic approaches with the potential to restore normoglycemia to patients with T2D.

Keywords

autonomic nervous system, central nervous system, diabetes, glucose effectiveness, glucose homeostasis, insulin-independent glucose disposal, therapeutics

Publication Date

1-6-2022

Publication Title

Annual review of pharmacology and toxicology

E-ISSN

1545-4304

Volume

62

First Page

55

Last Page

84

PubMed ID

34990204

Digital Object Identifier (DOI)

10.1146/annurev-pharmtox-052220-010446

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