However, although it is established that hyperglycemia requires β cell dysfunction to develop, the role of testosterone in β cell function is less understood. Severe testosterone deficiency predisposes men to type 2 diabetes (T2D), while in contrast, androgen excess predisposes women to hyperglycemia. One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose homeostasis by testosterone in male and females. Positive correlation between insulin sensitivity (M) and increase in testosterone post stimulation of… Our data also suggest that testosterone may affect insulin sensitivity both directly and indirectly. The normal aging process is accompanied by physiological changes in target organs that are sites of androgen action. However, the approval of a transdermal testosterone delivery system in the form of a gel meant that testosterone could now be administered easily, conveniently, and in a pain-free manner (3). For decades, the only method of delivering testosterone was through a deep, painful intramuscular injection every two weeks. A second important factor that contributed to the more widespread use of testosterone was the development of more patient-friendly formulations. While increasing awareness of and demand for a medication may be beneficial if the risk-benefit ratio of the drug is favorable, that assumption is questionable for many men taking testosterone for nonspecific symptoms without a clear diagnosis. When prescribing trends are compared between countries, it is evident that this increase in testosterone use was most marked in the United States, with relatively little change in the United Kingdom (1). T-increased levels by physical activity have been shown to play a key role in skeletal muscle tissue homeostasis, metabolism and recovery from exercise-induced stress 9–11, 23. I, targeting muscle, govern carbohydrate, lipid and protein metabolism , while T seemed to mainly affect the body composition . Skeletal muscle system, essential for the postural retention and locomotion has been shown to be an active organ able to dynamically respond to several molecules involved in the regulation of body metabolism, physiologic or pathologic processes, such as T and I, among other factors 5–7, 20, 21. Immunofluorescence analysis (a) revealed no signal for GLUT4 membrane expression in control (ctr) untreated Hfsmc; positive staining for GLUT4 was observed after 30-min incubation with I (100 nM) or T (100 nM) (upper panels). Effect of bicalutamide pre-treatment on testosterone-induced GLUT4 translocation in Hfsmc. Percentage analysis of GLUT4 positive cells shows that T-mediated GLUT4 translocation was induced by 99.3% ± 3.1 and 83.4 ± 9.9% in undifferentiated and in differentiated cells, respectively; P 2b). Immunofluorescence analysis (a) revealed no signal for GLUT4 membrane expression in control (ctr) untreated undifferentiated or differentiated Hfsmc; positive staining for GLUT4 was observed after 30-min incubation with I (100 nM) or T (100 nM) both in undifferentiated or differentiated conditions (upper panels). The effects of T onto I-related signal transduction pathways were investigated in undifferentiated Hfsmc cells treated with T for 15 min, 30 min, 2, 6 and 12 h vs. T0 (time before stimuli addition); 15 min I treatment was used as positive control. T insulin-like effects on human skeletal muscle cells has been not yet fully investigated. We know that acute physical exercise induces a rapid increase in the human serum endogenous levels of several circulating factors such as T 4–6, but the related short-term effects on T-targeted cells, such as skeletal muscle cells, have been not yet characterized. All together our data indicate that testosterone through the activation of non-genomic pathways, participates in skeletal muscle glucose metabolism by inducing insulin-related effects. GLUT4 cell expression, localization and the phosphorylation/activation of AKT, ERK, mTOR and GSK3β insulin-related pathways at different time points after treatment with testosterone were analyzed. A third of these genes code for proteins involved in inflammation and cellular stress, demonstrating that islets lacking AR are adapting to injury. This is consistent with the observation that male βARKO mice exhibit blunted GSIS and glucose intolerance in response to parenteral glucose, which does not activate gut GLP-1 secretion. Rather, testosterone enhances GSIS from cultured islets by increasing cAMP accumulation (Navarro et al., 2016).
