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 language | English |
|---|---|
| Pages (from-to) | 104-110 |
| Number of pages | 7 |
| Journal | Current Opinion in Nephrology and Hypertension |
| Volume | 24 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2014 |
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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 journal › Article
}
TY - JOUR
T1 - Insulin signaling
T2 - Implications for podocyte biology in diabetic kidney disease
AU - Coward, Richard
AU - Fornoni, Alessia
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Akt
KW - GLUT4
KW - Insulin signaling
KW - Intracellular lipids
KW - Mammalian target of rapamycin
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U2 - 10.1097/MNH.0000000000000078
DO - 10.1097/MNH.0000000000000078
M3 - Article
VL - 24
SP - 104
EP - 110
JO - Current Opinion in Nephrology and Hypertension
JF - Current Opinion in Nephrology and Hypertension
SN - 1062-4821
IS - 1
ER -