Abstract
Type 1 diabetes mellitus (insulin-dependent diabetes) is characterized by hyperglycemia caused by an insulin deficiency. Diabetic nephropathy is a major complication of hyperglycemia. 3,3′-diindolylmethane (DIM)-a natural compound produced from indole-3-carbinol, found in cruciferous vegetables-enhances glucose uptake by increasing the activation of the insulin signaling pathway in 3T3-L1 adipocytes. In this study, we investigated whether DIM could improve insulin-dependent diabetes and nephropathy in streptozotocin (STZ)-induced diabetic mice. In mice, STZ induced hyperglycemia, hunger, thirst, and abnormally increased kidney weight and serum creatinine, which is a renal functional parameter. DIM decreased STZ-increased high blood glucose levels and food and water intake in diabetic mice. DIM also improved diabetic nephropathy by inhibiting the expression of PKC-α, the marker of albuminuria, and TGF-β1, an indicator of renal hypertrophy, in diabetic mice. Our findings suggest that DIM may ameliorate hyperglycemia and diabetic nephropathy through the inhibition of PKC-α and TGF-β1 signaling.
Highlights
Type 1 diabetes mellitus is a chronic disease, which is characterized by insulin deficiency due to the loss of pancreatic β cells and the resultant abnormally high blood glucose [1,2]
1 diabetes mellitus is a metabolic disease resulting the destruction of insulincells in Type the pancreas, that leads to hyperglycemia
Type diabetes is characterized by hyperglycemia, thirst, hunger, and and weight loss, caused by insulin deficiency [1,2]
Summary
Type 1 diabetes mellitus is a chronic disease, which is characterized by insulin deficiency due to the loss of pancreatic β cells and the resultant abnormally high blood glucose [1,2]. Diabetic nephropathy is a major chronic complication, caused by uncontrolled hyperglycemia in type 1 diabetes [3,4] Pathological changes, such as glomerular hypertrophy, mesangial cell expansion, and tubulointerstitial fibrosis, occur during the progression of diabetic nephropathy [4,5]. Previous studies have found that DIM can improve type 2 diabetes by enhancing glucose uptake through activation of insulin signaling in 3T3-L1 cells, by lowering plasma glucose uptake through the the activation of insulin signaling in 3T3-L1 cells, andand by lowering thethe plasma glucose levels in high-fat-diet-fed obese mice [13,14]. In toxic to the insulin-producing pancreatic ββ cells, this study, study, our ourgoal goalwas wastotodetermine determinewhether whether In this andand nephropathy in mice, as well as to elucidate its underlying mechanism.
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