Insulin signaling

Implications for podocyte biology in diabetic kidney disease

Richard Coward, Alessia Fornoni

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Purpose of review Several key elements of the insulin signaling cascade contribute to podocyte function and survival. While it was initially thought that the consequences of altered insulin signaling to podocyte function was strictly related to altered glucose uptake, it has become clear that upstream signaling events involved in cell survival, lipid metabolism or nutrient sensing and modulated by insulin are strong independent contributors to podocyte function. Recent findings Akt2, the major isoform of Akt activated following cellular insulin stimulation, protects against the progression of renal disease in nephron-deficient mice, and podocyte-specific deletion of Akt2 results in a more rapid progression of experimental glomerular disease. In diabetes, podocyte mammalian target of rapamycin activation clearly contributes to podocyte injury and regulated autophagy. Furthermore, podocyte-specific glucose transporter type 4 (GLUT4) deficiency protects podocytes by preventing mammalian target of rapamycin signaling independently of glucose uptake. Finally, intracellular lipids have been recently recognized as major modulators of podocyte insulin signaling and as a new therapeutic target. Summary The identification of new contributors to podocyte insulin signaling is of extreme translational value as it may lead to new drug development strategies for diabetic kidney disease, as well as for other proteinuric kidney diseases.

Original languageEnglish
Pages (from-to)104-110
Number of pages7
JournalCurrent Opinion in Nephrology and Hypertension
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint

Podocytes
Diabetic Nephropathies
Insulin
Sirolimus
Glucose Transporter Type 4
Glucose
Nephrons
Autophagy
Kidney Diseases
Lipid Metabolism
Disease Progression
Cell Survival
Protein Isoforms
Kidney
Lipids
Food

Keywords

  • Akt
  • GLUT4
  • Insulin signaling
  • Intracellular lipids
  • Mammalian target of rapamycin

ASJC Scopus subject areas

  • Nephrology
  • Internal Medicine

Cite this

Insulin signaling : Implications for podocyte biology in diabetic kidney disease. / Coward, Richard; Fornoni, Alessia.

In: Current Opinion in Nephrology and Hypertension, Vol. 24, No. 1, 01.01.2014, p. 104-110.

Research output: Contribution to journalArticle

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