title: Testosterone protects against glucotoxicity-induced apoptosis of pancreatic β-cells (INS-1) and male mouse pancreatic islets.
abstract: Male hypogonadism associates with type 2 diabetes, and T can protect pancreatic β-cells from glucotoxicity. However, the protective mechanism is still unclear. This study thus aims to examine the antiapoptotic mechanism of T in pancreatic β cells cultured in high-glucose medium. T (0.0005-2 μg/mL) was added to INS-1 cells cultured in basal glucose or high-glucose media. Then cellular apoptosis, oxidative stress, and cell viability were measured. Endoplasmic reticulum (ER) stress markers and sensors and the antiapoptotic protein (B-cell lymphoma 2) were investigated by real-time PCR and Western blot analysis. ER stress markers were also measured in male mouse pancreatic islet cultured in similar conditions. T (0.05 and 0.5 μg/mL) did not have any effect on apoptosis and viability of INS-1 cells cultured in basal glucose medium, but it could reduce apoptosis and increase viability of INS-1 cells cultured in high-glucose medium. The protective effect of T is diminished by androgen receptor inhibitor. T (0.05 μg/mL) could significantly reduce nitrotyrosine levels, mRNA, and protein levels of the ER stress markers and sensor those that were induced when INS-1 cells were cultured in high-glucose medium. It could also significantly increase the survival proteins, sarco/endoplasmic reticulum Ca(2+) ATPase-2, and B-cell lymphoma 2 in INS-1 cells cultured in the same conditions. Similarly, it could reduce ER stress markers and increase sarco/endoplasmic reticulum Ca(2+) ATPase protein levels in male mouse pancreatic islets cultured in high-glucose medium. T can protect against male pancreatic β-cell apoptosis from glucotoxicity via the reduction of both oxidative stress and ER stress.
authors: MD, PhD, Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. siskw@mahidol.ac.th.
authors: Wanthanee
authors: W
authors: Hanchang
authors: Namoiy
authors: N
authors: Semprasert
authors: Thawornchai
authors: T
authors: Limjindaporn
authors: Pa-thai
authors: PT
authors: Yenchitsomanus
authors: Suwattanee
authors: S
authors: Kooptiwut
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000008:administration & dosage / Q000633:toxicity*; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011944:Receptors, Androgen; D013312:Stress, Physiological / Q000187:drug effects; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D011944:Receptors, Androgen; D013739:Testosterone; D005947:Glucose