Cx30.2 deletion causes imbalances in testicular Cx43, Cx46, and Cx50 and insulin receptors. Reciprocally, diabetes/obesity alters Cx30.2 in mouse testis

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 318; no. 6; pp. R1078 - R1090
• Main Authors: Pelletier, R-Marc, Layeghkhavidaki, Hamed, Kumar, Nalin M, Vitale, María Leiza
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.06.2020
• Series: Hormones, Reproduction and Development
• Subjects: Animals; Connexin 43 - genetics; Connexin 43 - metabolism; Connexins - genetics; Connexins - metabolism; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Gene Expression Regulation; Male; Mice; Mice, Knockout; Obesity - genetics; Obesity - metabolism; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; Testis - metabolism; sertoli cells; testis; connexions; germ cells
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00044.2020

Cx30.2 protein content and localization were assessed during development. An account of Cx30.2, Cx43, Cx46, and Cx50, and insulin receptor (IR) responses to , , or deficiency in mouse interstitial tissue (ITf)- and seminiferous tubule-enriched fractions (STf) is given. The impact of high glucose/insulin on Cx30.2 was investigated in spontaneously diabetic and obese and mouse testis and anterior pituitary (AP). Cx30.2 labeled contacts in vascular endothelial and Leydig cells and Sertoli cell junctions in stage V-VII. Cx30.2 expression is regulated differently in the interstitium and tubules. Cx30.2 at 30-kDa levels peaked by 28 days in ITf and by 14 days in STf. In STf, deleting decreased Cx43 and Cx50, whereas deleting downregulated Cx30.2. The opposite occurred in ITf. In STf, deleting upregulated Cx46 except the full-length reciprocally, deleting upregulated Cx30.2. In ITf, deficiency upregulated full-length and phosphorylated Cx46, whereas deleting downregulated 48- to 50-kDa Cx30.2. The and mouse ITf, STf, and AP showed imbalanced Cx30.2 levels. IRα levels at 135 kDa declined in and mouse ITf and and Cx50-/- STf. IRβ at 98 to 110 kDa dropped in and mice STf suggesting that deficiency decreases active IR sites. The results show the connexins interdependence and interaction and that altering a single connexin changes the remaining connexins expression, which can modify gap junction-mediated glucose exchanges in contacting cells. Data suggest that glucose/insulin influences Cx30.2 turnover in testis and AP and, reciprocally, that connexins modulate testis glucose uptake and response to insulin.