Role of Sex Steroids in β Cell Function, Growth, and Survival

Abstract

The gonads have long been considered as endocrine glands producing sex steroids such as estrogens, androgens and progesterone, for the sole purpose of sexual differentiation, puberty and reproduction. Reproduction and energy metabolism are tightly linked, however, and gonadal steroids play an important role in sex-specific aspects of energy metabolism in different physiological conditions. In that respect, gonadal steroids also influence the secretion of insulin in a sex-specific manner. This review presents a perspective on the physiological roles of estrogen, androgen and progesterone via their receptors in pancreatic β-cells in the gender-specific tuning of insulin secretion. We also discuss potential gender-specific therapeutic avenues that this knowledge may open in the future.

Early weaning induces short‐ and long‐term effects on pancreatic islets in Wistar rats of both sexes

“…Oestrogen directly stimulates insulin secretion by pancreatic β‐cells and improves peripheral insulin sensitivity (Mauvais‐Jarvis et al . ). We did not perform in vivo experiments to investigate the direct effect of oestrogen in insulin secretion in the EW model, which is a limitation of our study.…”

“…Some studies have addressed the role of sex steroids on pancreatic β‐cells (Nadal et al . ; Mauvais‐Jarvis, ). Oestrogens act on the pancreatic islets by binding to their α‐type receptors, resulting in increased biosynthesis and glucose‐stimulated insulin secretion (Nadal et al .…”

“…In addition, it is known that sexual maturation in adolescence increases insulin needs due to the rapid growth and development that occur during this particular phase of life (Amiel et al 1986). Some studies have addressed the role of sex steroids on pancreatic β-cells (Nadal et al 2009;Mauvais-Jarvis, 2016). Oestrogens act on the pancreatic islets by binding to their α-type receptors, resulting in increased biosynthesis and glucose-stimulated insulin secretion (Nadal et al 2009).…”

“…In premenopausal women, elevated oestradiol levels are observed, which is related to the lower prevalence of glucose intolerance compared to men of the same age (Zhu et al 2014). On the other hand, the beneficial effects of oestrogen are reduced after menopause in humans or in ovariectomized rats, which is accompanied by increases in visceral fat pad production, glucose intolerance and pancreatic β-cell failure, abruptly reducing insulin secretion and leading to an increased risk to T2DM (Brussaard et al 1997;Le May et al 2006;Mauvais-Jarvis, 2016).…”

Androgen receptor-deficient islet β-cells exhibit alteration in genetic markers of insulin secretion and inflammation. A transcriptome analysis in the male mouse

“…We reported that testosterone action on AR β-cells amplifies the insulinotropic action of GLP-1 on its receptor via a cAMP-dependent protein kinase-A pathway (Navarro et al, 2016). Thus, androgen deficiency predisposes to T2D via the combination of loss of androgen action in peripheral tissues producing insulin resistance and loss of androgen action in β-cells producing β-cell failure to compensate for insulin resistance (Mauvais-Jarvis, 2016b; Navarro et al, 2015; Navarro et al, 2016). …”