Amelioration of Hyperglycemia-Induced Nephropathy by 3,3'-Diindolylmethane in Diabetic Mice

Molecules. 2019 Dec 6;24(24):4474. doi: 10.3390/molecules24244474.

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.

Keywords: 3,3′-diindolylmethane; PKC-α; TGF-β1; hyperglycemia; nephropathy.

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Creatinine / blood
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / etiology*
  • Hyperglycemia / blood
  • Hyperglycemia / complications*
  • Hypoglycemic Agents / therapeutic use*
  • Indoles / chemistry*
  • Indoles / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protein Kinase C-alpha / blood
  • Transforming Growth Factor beta1 / chemistry

Substances

  • 3,3-diindolymethane
  • Blood Glucose
  • Hypoglycemic Agents
  • Indoles
  • Transforming Growth Factor beta1
  • Creatinine
  • Protein Kinase C-alpha