Combination Therapy with Vitamin D and Metformin: A Potential Approach to Mitigate Testicular Dysfunction in Type 2 Diabetes Mellitus
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Date
2024-09-25
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Reproductive Sciences
Abstract
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 fndings have associated long-term metformin intake with progressive oxidative pancreatic β
cell damage as the disease progresses. Hence, a signifcant number of patients treated with MET need an alternate therapy.
Hence, identifying drug combinations that can efectively alleviate diferent 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 efect
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 sacrifced using IP injection of ketamine and xylaxine (40 and 4 mg/kg respectively). Vitamin D improved the
ameliorative efect of metformin on T2DM-induced hyperglycemia and lipid dysmetabolism, accompanied by a signifcant
decrease in testicular lactate dehydrogenase and lactate. Also, vitamin D + metformin signifcantly increased serum lutein-
izing hormone, follicle-stimulating hormone, testosterone, and testicular 5α reductase activities. Furthermore, vitamin D
improved the anti-infammatory and antioxidant efects of metformin by signifcantly 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 efect of
metformin on T2DM-induced testicular dysfunction.
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High fat diet · Streptozotocin · Vitamin D · Metabolic syndrome · Micronutrient · Testis