Testosterone Rapidly Stimulates Insulin Release from Isolated Pancreatic Islets through a Non-genomic Dependent Mechanism

Abstract

The action of testosterone on the 45Ca2+ uptake and insulin secretion was studied in short-term experiments using isolated pancreatic islets of Langerhans. Testosterone (1 microM) stimulated 45Ca2+ uptake within 60 seconds of incubation on similar proportion than tolbutamide. Also, the hormone rapidly increased insulin release (34%; 180 seconds) on the presence of non-stimulatory concentrations of glucose (3 mM). Impermeant testosterone-BSA significantly stimulated the secretion of insulin to a lower percentage (10%). The action of the hormone is specific--neither 17beta-E2 nor progesterone stimulated insulin secretion in the presence of 3 mM glucose. The action of testosterone on insulin secretion was dose-dependent, and at rat plasma physiological concentrations (25 nM), stimulus was 17% (p < 0.05). In conclusion, in isolated pancreatic islets experiments, physiological concentration of testosterone rapidly stimulate insulin secretion and 45Ca2+ uptake through a membrane bound mechanism.

Elevated androgen levels induce hyperinsulinemia through increase in Ins1 transcription in pancreatic beta cells in female rats†

“…Evidence indicates that androgens have paradoxical ability to induce apoptosis [48], inhibit proliferation [49] and expand islets [50]. Murine studies have demonstrated severely limited beta cell proliferation with advancing age [51,52]. The lack of increased proliferation of β cells in hyperinsulinemic DHT females illustrates this as well; the adaptation to produce more insulin appears to come from hypersecretive islets rather than an increased number or area of islets.…”

Sex steroids effects on the endocrine pancreas

“…In isolated islets, physiological concentrations of testosterone within 60 s stimulate insulin secretion and Ca2+ uptake in presence of non-stimulatory concentration of glucose [91]. On the other hand, dehydroepiandrosterone decreased agonist-induced Ca2+ release by a rapid, non-genomic mechanism in INS-1 cells, and inhibited insulin secretion induced by carbachol (an agonist of insulin secretion).…”

5α-androstane-3α,17β-diol selectively activates the canonical PI3K/AKT pathway: a bioinformatics-based evidence for androgen-activated cytoplasmic signaling

“…Although AR-dependent genomic action may ultimately turn out to be the most important for physiological development of androgen target tissues (Whitacre et al 2002;Cheng et al 2006), 5a-DHT-activated non-genomic action has been strongly implicated in pathological progression of androgen-independent prostate cancer (Sun et al 2006;Cinar et al 2007). In the mode of non-genomic action, it has been proposed that androgens may act as mediators of secondary transcription factors, as regulators of autocrine and paracrine mediators of gene expression, or as mediators in secretion of other hormones that regulate androgenic effects in androgen target tissues (Verhoeven and Swinnen 1999;Grillo et al 2005). Some of these effects have been attributed to membrane AR (Papakonstanti et al 2003;Grillo et al 2005) or other plasma membrane bound receptors (Lieberherr and Grosse 1994;Estrada et al 2003).…”

“…In the mode of non-genomic action, it has been proposed that androgens may act as mediators of secondary transcription factors, as regulators of autocrine and paracrine mediators of gene expression, or as mediators in secretion of other hormones that regulate androgenic effects in androgen target tissues (Verhoeven and Swinnen 1999;Grillo et al 2005). Some of these effects have been attributed to membrane AR (Papakonstanti et al 2003;Grillo et al 2005) or other plasma membrane bound receptors (Lieberherr and Grosse 1994;Estrada et al 2003).…”