Diabetes Type 1 Negatively Influences Leydig Cell Function in Rats, Which is Partially Reversible by Insulin Treatment

Isabel Viola Wagner*, Nora Klöting, Iuliia Savchuk, Lisa Eifler, Alexandra Kulle, Susan Kralisch-Jäcklein, Jörg Dötsch, Olaf Hiort, Konstantin Svechnikov, Olle Söder

*Corresponding author for this work


Type 1 diabetes mellitus (T1DM) is associated with impaired spermatogenesis and lower testosterone levels and epididymal weight. However, the underlying processes in the testis are unknown and remain to be elucidated. Therefore, the present study focused on the effects of T1DM on testicular function in a spontaneously diabetic rat model. BB/OKL rats after diabetes manifestation were divided into 3 groups: those without insulin treatment and insulin treatment for a duration of 2 and of 6 weeks. Anthropometrical data, circulating levels of gonadotrophins, testosterone, and inhibin B were measured. Intratesticular testosterone, oxidative stress, inflammation, and apoptosis were analyzed. Key enzymes of steroidogenesis were evaluated in the testis. Untreated diabetic rats had significantly lower serum follicle-stimulating hormone and luteinizing hormone levels. Serum and intratesticular testosterone levels significantly decreased in untreated diabetic rats compared to healthy controls. Key markers of Leydig cell function were significantly downregulated at the RNA level: insulin-like factor 3 (Insl3) by 53% (P=.006), Star by 51% (P=.004), Cyp11A1 by 80% (P=.003), 3Beta-Hsd2 by 61% (P=.005), and Pbr by 52% (P=.002). In the insulin-treated group, only Cyp11A1 and 3Beta-Hsd2 transcripts were significantly lower. Interestingly, the long-term insulin-treated group showed significant upregulation of most steroidogenic enzymes without affecting testosterone levels. Tumor necrosis factor α and apoptosis were significantly increased in the long-term insulin-treated rats. In conclusion T1DM, with a severe lack of insulin, has an adverse action on Leydig cell function. This is partially reversible with well-compensated blood glucose control. Long-term T1DM adversely affects Leydig cell function because of the process of inflammation and apoptosis.

Original languageEnglish
Article numberbqab017
JournalEndocrinology (United States)
Issue number4
Publication statusPublished - 01.04.2021

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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