We investigated whether 1,25-dihydroxy-vitamin D (1,25(OH)D) could improve early diabetic nephropathy through the DNA-damage-inducible transcript 4/tuberous sclerosis 2/mammalian target of rapamycin pathway. Rat mesangial cells were cultured in media containing normal glucose or high glucose and were treated with or without 1,25(OH)D. Mesangial cells proliferation was measured. Streptozotocin-induced diabetic rats were injected intravenously with a recombinant lentivirus against the rat vitamin D receptor gene. Urinary and serum albumin, fasting plasma glucose, serum triglyceride, total cholesterol, calcium, parathyroid hormone and serum 25-dihydroxy-vitamin D (25(OH)D) levels, mean glomerular volume, glomerular basement membrane thickness and total kidney volume were determined. The expressions of vitamin D receptor, DNA-damage-inducible transcript 4, and mammalian target of rapamycin were measured. 1,25(OH)D inhibited the proliferation of mesangial cells induced by hyperglycemia. 1,25(OH)D also significantly reduced albumin excretion, mean glomerular volume, glomerular basement membrane, and total kidney volume in rats with diabetic nephropathy. The expression of DNA-damage-inducible transcript 4 was elevated by 1,25(OH)D treatment. The phosphorylation of mammalian target of rapamycin was reduced by 1,25(OH)D treatment. Vitamin D receptor gene silencing blocked all of the above results. The current study demonstrates that 1,25(OH)D can effectively inhibit mesangial cells proliferation induced by hyperglycemia, thus suppressing the development of diabetic nephropathy. This study also shows that the nephron-protective effect of 1,25(OH)D occurs partly through the DDIT4/TSC2/mTOR pathway.
We assessed the correlation between the visceral adiposity index (VAI; a useful indicator of adipose distribution and function) and homeostatic model assessment of insulin resistance (HOMA-IR) in participants with normal waist circumference. A cross-sectional study was conducted, which included 1834 Chinese adults. The blood pressure, anthropometric measurements, fasting and postprandial blood glucose, fasting insulin, and lipid profiles were measured. The VAI and HOMA-IR were calculated. Participants were divided into 4 groups according to the HOMA-IR level, and the correlation between the VAI and HOMA-IR was analyzed. The VAI gradually increased across the HOMA-IR quartiles ( P < .05), and a Pearson correlation analysis showed that VAI was positively related to the HOMA-IR ( P < .001) in males and females. After adjusting for the other covariates, VAI was independently correlated with the HOMA-IR. A logistic regression analysis indicated that VAI elevation was the main risk factor for the increased HOMA-IR in both genders. Overall, the VAI was closely correlated with the HOMA-IR in a population without central obesity.
The present study demonstrates that 1,25(OH) D treatment has the potential to improve diabetic cardiomyopathy in rats and suggests that VD-VDR signaling induces this protective effect against diabetic cardiomyopathy might partly through the PARP1/SIRT1/mTOR pathway.
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