Combination Therapy with Vitamin D and Metformin: A Potential Approach to Mitigate Testicular Dysfunction in Type 2 Diabetes Mellitus

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2024-12, Vol.31 (12), p.3795-3807
• Main Authors: Odetayo, Adeyemi Fatai, Abdulrahim, Halimat Amin, Yusuf, Adedotun Muiz, Aromokhame, Williams Oshetename, Olaitan, Ademola Muritala, Ugoji, Mirabel Chisom, Hamed, Moses Agbomhere, Olayaki, Luqman Aribidesi
• Format: Article
• Language: English
• Subjects: Animals; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Drug Therapy, Combination; Embryology; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacology; Infertility: Original Article; Male; Medicine; Medicine & Public Health; Metformin - administration & dosage; Metformin - pharmacology; Obstetrics/Perinatology/Midwifery; Oxidative Stress - drug effects; Rats; Rats, Wistar; Reproductive Medicine; Testicular Diseases - drug therapy; Testicular Diseases - etiology; Testicular Diseases - prevention & control; Testis - drug effects; Testis - metabolism; Testosterone - blood; Vitamin D - administration & dosage
• ISSN: 1933-7191; 1933-7205; 1933-7205
• DOI: 10.1007/s43032-024-01708-3

Type 2 diabetes mellitus (T2DM) is a multifactorial disease that cannot be linked to a single pathway, causing the observed heterogeneity among T2DM patients. Despite this level of heterogeneity, T2DM is majorly managed by metformin (MET) monotherapy. However, recent findings have associated long-term metformin intake with progressive oxidative pancreatic β cell damage as the disease progresses. Hence, a significant number of patients treated with MET need an alternate therapy. Hence, identifying drug combinations that can effectively alleviate different diabetes complications would serve as a more promising therapy that can translate into active use. Hence, this study was designed to explore the possible synergistic effect of vitamin D and metformin on T2DM-induced testicular dysfunction. Thirty healthy male Wistar rats (weight: 120-150 g and age: 10 ± 2 weeks) were randomly divided into control, diabetes untreated (HFD+STZ), diabetes + vitamin D (1000 IU/kg), diabetes + metformin (180 mg/kg), and diabetes + vitamin D + metformin. All treatments lasted for 28 days and animals were sacrificed using IP injection of ketamine and xylaxine (40 and 4 mg/kg respectively). Vitamin D improved the ameliorative effect of metformin on T2DM-induced hyperglycemia and lipid dysmetabolism, accompanied by a significant decrease in testicular lactate dehydrogenase and lactate. Also, vitamin D + metformin significantly increased serum luteinizing hormone, follicle-stimulating hormone, testosterone, and testicular 5α reductase activities. Furthermore, vitamin D improved the anti-inflammatory and antioxidant effects of metformin by significantly decreasing T2DM-induced increase in testicular interleukin 1beta, interleukin 6, TNF-α, nitric oxide, and NF-κB and increasing T2DM-induced decrease in interleukin 10, glutathione, superoxide dismutase, catalase, GPx, and Nrf2. Vitamin D enhanced the ameliorative effect of metformin on T2DM-induced testicular dysfunction.