Podocyte-specific GLUT4-deficient mice have fewer and larger podocytes and are
protected from diabetic nephropathy.
Authors Guzman J, Jauregui AN, Merscher-Gomez S, Maiguel D, Muresan C, Mitrofanova A,
Diez-Sampedro A, Szust J, Yoo TH, Villarreal R, Pedigo C, Molano RD, Johnson K,
Kahn B, Hartleben B, Huber TB, Saha J, Burke GW, Abel ED, Brosius FC, Fornoni A
Submitted By Alessia Fornoni on 3/17/2014
Status Published
Journal Diabetes
Year 2014
Date Published 2/1/2014
Volume : Pages 63 : 701 - 714
PubMed Reference 24101677
Abstract Podocytes are a major component of the glomerular filtration barrier, and their
ability to sense insulin is essential to prevent proteinuria. Here we identify
the insulin downstream effector GLUT4 as a key modulator of podocyte function in
diabetic nephropathy (DN). Mice with a podocyte-specific deletion of GLUT4 (G4
KO) did not develop albuminuria despite having larger and fewer podocytes than
wild-type (WT) mice. Glomeruli from G4 KO mice were protected from
diabetes-induced hypertrophy, mesangial expansion, and albuminuria and failed to
activate the mammalian target of rapamycin (mTOR) pathway. In order to
investigate whether the protection observed in G4 KO mice was due to the failure
to activate mTOR, we used three independent in vivo experiments. G4 KO mice did
not develop lipopolysaccharide-induced albuminuria, which requires mTOR
activation. On the contrary, G4 KO mice as well as WT mice treated with the mTOR
inhibitor rapamycin developed worse adriamycin-induced nephropathy than WT mice,
consistent with the fact that adriamycin toxicity is augmented by mTOR
inhibition. In summary, GLUT4 deficiency in podocytes affects podocyte nutrient
sensing, results in fewer and larger cells, and protects mice from the
development of DN. This is the first evidence that podocyte hypertrophy
concomitant with podocytopenia may be associated with protection from

Investigators with authorship
E. Dale AbelUniversity of Iowa
Frank BrosiusUniversity of Arizona
Alessia FornoniUniversity of Miami - Medical Campus