Related Experiment Video

Updated: Nov 23, 2025

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
10:31

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

Published on: May 2, 2025

456

Proximal tubular epithelial insulin receptor mediates high-fat diet-induced kidney injury

Hak Joo Lee1, Meenalakshmi M Mariappan1, Luke Norton2

  • 1Center for Renal Medicine, Division of Nephrology.

JCI Insight
|January 5, 2021
PubMed

Insights

Obesity-induced kidney injury in males requires insulin receptor (IR) activation in kidney proximal tubules. Blocking IR in these tubules ameliorates high-fat diet-induced kidney damage.

Area of Science:

  • Nephrology
  • Endocrinology
  • Metabolic Syndrome

Background:

  • Obesity is linked to kidney injury, with hyperinsulinemia potentially playing a role.
  • The specific contribution of insulin receptor (IR) activation in kidney proximal tubules to this injury remains unclear.

Purpose of the Study:

  • To investigate the role of kidney proximal tubule epithelial IR in obesity-induced kidney injury.
  • To determine if blocking IR in kidney proximal tubules can prevent high-fat diet (HFD)-induced kidney damage.

Main Methods:

  • Administered normal-fat diet (NFD) or HFD to control and kidney proximal tubule IR-knockout (KPTIRKO) mice for 4 months.
  • Assessed kidney injury markers, metabolic parameters, blood pressure, and renal IR signaling pathways.
  • Compared outcomes between genotypes and sexes.

Main Results:

  • HFD increased kidney injury markers (urinary albumin-to-creatinine ratio, kidney injury molecule-1), matrix proteins, and systolic blood pressure in male control mice.
  • These HFD-induced changes were significantly ameliorated in male KPTIRKO mice.
  • Female mice of both genotypes were resistant to HFD-induced kidney injury.

Conclusions:

  • Activation of kidney proximal tubule IR is essential for HFD-induced kidney injury in male mice.
  • Targeting IR in kidney proximal tubules may offer a therapeutic strategy for obesity-related kidney disease in males.
  • Sex differences exist in susceptibility to HFD-induced kidney injury.
Keywords:
Insulin signalingNephrologyObesity

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