Relationships between diabetic nephropathy and insulin resistance, inflammation, Trx, Txnip, CysC and serum complement levels

Eur Rev Med Pharmacol Sci. 2020 Nov;24(22):11700-11706. doi: 10.26355/eurrev_202011_23815.

Abstract

Objective: To investigate the relationships between diabetic nephropathy (DN) and insulin resistance, inflammation, thioredoxin (Trx), thioredoxin-interacting protein (Txnip), Cystatin C (CysC) and serum complement levels.

Patients and methods: A total of 119 patients with type 2 diabetes mellitus (T2DM) treated in the Endocrinology Department of our hospital from January 2017 to December 2017 were enrolled as the experiment group, while 30 healthy volunteers were selected as the control group. The expression levels of inflammatory factors, Trx, Txnip, CysC and serum complements in every subject were detected. In addition, the type 2 diabetic nephropathy rat model was established via high-fat diet and injection of low-dose streptozotocin. Blood glucose, insulin resistance indexes and 24h-urinary albumin excretion were measured, and the histomorphological characteristics of the kidney in animals were observed.

Results: In clinical subjects, Trx level was notably lower in the simple DM group, early DN group and clinical DN group in comparison with that in the control group. The levels of Txnip and CysC in the simple DM group, early DN group and clinical DN group were remarkably higher than those in the control group. Moreover, the expression levels of TNF-α and IL-6 in the clinical DN group were significantly elevated compared with those in the simple DM group and early DN group. In addition, C1q expression in the clinical DN group was higher than that in the simple DM group and early DN group. In model rats, HOMA-IR was distinctly higher in the DM group and DN group than that in the control group. The ratio of kidney weight to body weight (KW/BW) was evidently higher in the DN group in comparison with that in the control group and DM group.

Conclusions: Insulin resistance, inflammatory factors, and levels of Trx, Txnip, CysC and serum complement C1q are related to the progression of DM.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Carrier Proteins / analysis
  • Cell Cycle Proteins / analysis
  • Complement C1q / analysis
  • Cystatin C / analysis
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / pathology*
  • Diabetic Nephropathies / chemically induced
  • Diabetic Nephropathies / pathology*
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Humans
  • Inflammation / chemically induced
  • Inflammation / pathology*
  • Insulin Resistance
  • Intracellular Signaling Peptides and Proteins / analysis
  • Male
  • Membrane Proteins / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin / administration & dosage
  • Thioredoxins / analysis

Substances

  • Blood Glucose
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cystatin C
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • TXNIP protein, human
  • TXNIP protein, rat
  • Txn1 protein, rat
  • VAC14 protein, human
  • Thioredoxins
  • Streptozocin
  • Complement C1q