{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:39:13Z","timestamp":1787510353311,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,4,5]],"date-time":"2020-04-05T00:00:00Z","timestamp":1586044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Department of Science and Technology, New Delhi, India","award":["INT\/RUS\/RFBR\/P-310"],"award-info":[{"award-number":["INT\/RUS\/RFBR\/P-310"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Diabetes mellitus impairs testicular activity and leads to infertility. Leptin is one of the endogenous regulators of the male reproductive functions, but the role of leptin and its receptor (LEPR\/Ob\u2010R) in the control of testosterone production and testicular proliferation has not been investigated so far, especially in the Type 1 diabetes mellitus (DM1). Metformin is an anti\u2010hyperglycemic drug which is beneficial for treating the both DM2 and DM1. The aim of this work was to study the possible role of leptin and Ob\u2010R in the regulation of steroidogenesis and proliferation in the testes of mice with streptozotocin\u2010induced DM1 (75\u2009mg\/kg\/day, 4 days) and to estimate the restoring effect of metformin treatment (500\u2009mg\/kg, 2 weeks) on the diabetic testes. In the diabetic testes, the plasma and intratesticular leptin levels and plasma testosterone levels were reduced and completely restored by metformin treatment. Metformin also restored the expression of the steroidogenic transport protein steroidogenic acute regulatory protein reduced in DM1. In the diabetic testes, the expression of Ob\u2010R was downregulated and the immunolocalization of Ob\u2010R showed weak staining in the Leydig cells, the primary spermatocytes and the round spermatids. The germ cell proliferation was also reduced in DM1, as noticed with proliferating cell nuclear antigen (PCNA) expression. Metformin increased the Ob\u2010R expression and immunostaining in the different cell types and improved the PCNA expression. Thus, DM1 impairs the testicular steroidogenesis and proliferation by inhibiting the leptin signaling, causing a decrease in leptin levels and Ob\u2010R expression in the testes of diabetic mice, while metformin improves the leptin signaling and restores testosterone production and testicular proliferation.<\/jats:p>","DOI":"10.1002\/mrd.23342","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T00:33:25Z","timestamp":1586133205000},"page":"620-629","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Effect of metformin on testicular expression and localization of leptin receptor and levels of leptin in the diabetic mice"],"prefix":"10.1002","volume":"87","author":[{"given":"Lalrawngbawli","family":"Annie","sequence":"first","affiliation":[{"name":"Department of Zoology Mizoram University Aizawl Mizoram India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malsawmhriatzuala","family":"Jeremy","sequence":"additional","affiliation":[{"name":"Department of Zoology Mizoram University Aizawl Mizoram India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guruswami","family":"Gurusubramanian","sequence":"additional","affiliation":[{"name":"Department of Zoology Mizoram University Aizawl Mizoram India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira V.","family":"Derkach","sequence":"additional","affiliation":[{"name":"IM Sechenov Institute of Evolutionary Physiology and Biochemistry, Laboratory of Molecular Endocrinology Russian Academy of Sciences  St. Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander O.","family":"Shpakov","sequence":"additional","affiliation":[{"name":"IM Sechenov Institute of Evolutionary Physiology and Biochemistry, Laboratory of Molecular Endocrinology Russian Academy of Sciences  St. Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-5529","authenticated-orcid":false,"given":"Vikas Kumar","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Zoology Mizoram University Aizawl Mizoram India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/tisb.23992"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-S067"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0102-865020160060000008"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.5603\/FHC.a2015.0005"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.105569"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.007831"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/19396368.2014.885995"},{"issue":"9","key":"e_1_2_7_10_1","first-page":"1179","article-title":"Steroidogenesis and\u00a0spermatogenesis in male mice with streptozotocin diabetes mellitus","volume":"105","author":"Derkach K. 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