Emerging role of testosterone in pancreatic β cell function and insulin secretion - PubMed (original) (raw)

Review

Emerging role of testosterone in pancreatic β cell function and insulin secretion

Weiwei Xu et al. J Endocrinol. 2019 Mar.

Abstract

One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose homeostasis by testosterone in male and females. Severe testosterone deficiency predisposes men to type 2 diabetes (T2D), while in contrast, androgen excess predisposes women to hyperglycemia. The role of androgen deficiency and excess in promoting visceral obesity and insulin resistance in men and women respectively is well established. However, although it is established that hyperglycemia requires β cell dysfunction to develop, the role of testosterone in β cell function is less understood. This review discusses recent evidence that the androgen receptor (AR) is present in male and female β cells. In males, testosterone action on AR in β cells enhances glucose-stimulated insulin secretion by potentiating the insulinotropic action of glucagon-like peptide-1. In females, excess testosterone action via AR in β cells promotes insulin hypersecretion leading to oxidative injury, which in turn predisposes to T2D.

Keywords: androgen receptor; diabetes; islet cells; sex dimorphism; testosterone.

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Conflict of interest statement

Declaration of interest

The author declares no conflict of interest

Figures

Figure 1.

Figure 1.. Mechanism of testosterone insulinotropic action in β cell.

Testosterone action on an extranuclear AR in β cell amplifies the insulinotropic action of islet-derived GLP-1 via increasing cAMP production and PKA activation.

Figure 2.

Figure 2.. Mechanism of diabetes in men with androgen deficiency.

Moderate androgen deficiency during aging predisposes men to increased adiposity and insulin resistance leading to metabolic syndrome. During severe androgen deficiency such as androgen depletion therapy (ADT), the additional β cell dysfunction predisposes to diabetes.

Figure 3.

Figure 3.. Summary of the bi-directional modulation of β cell function in males and females.

In males testosterone action in β cells increases GSIS by enhancing GLP-1 insulinotropic action, prevents inflammation and promote β cell health. In females, testosterone excess in β cells promotes insulin hypersecretion, mitochondrial dysfunction, oxidative stress and predisposes to β cell dysfunction and failure.

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