NDT Advance Access published online on January 31, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfk089
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1 Department of Clinical Sciences, ‘La Sapienza’ University, Rome, Italy
* To whom correspondence should be addressed. Background. GLUT1 upregulation and increased glucose transport activity may contribute to extracellullar matrix (ECM) accumulation characterizing diabetic nephropathy (DN). Rats of the Milan hypertensive strain (MHS) are resistant to both hypertensive and diabetic renal disease, due to a haemodynamic protection. On the contrary, those of the Milan normotensive strain (MNS) develop spontaneous glomerulosclerosis, and when rendered diabetic, show typical morphological and haemodynamic changes. Methods. To assess whether susceptibility to diabetic glomerulopathy in MNS rats is associated with higher glucose transporter 1 (GLUT1) expression (and glucose transport activity) vs MHS rats, diabetic and nondiabetic MNS and MHS rats were followed for 6 months and mesangial cells derived from these animals were exposed to high glucose (HG) vs normal glucose (NG) conditions. Results. Glomerular expression of GLUT1 protein and ECM and transforming growth factor- Conclusions. These data indicate that susceptibility to diabetic glomerulopathy in MNS rats is associated with increased GLUT1-dependent glucose transport activity in response to hyperglycaemia and/or TGF-
Received October 3, 2005
Accepted January 3, 2006
Original Article
Role of TGF-
Carlo Ricci 1,
Carla Iacobini 2,
Giovanna Oddi 2,
Lorena Amadio 2,
Stefano Menini 1,
Maria Pia Rastaldi 3,
Aurora Frasheri 1,
Flavia Pricci 4,
Francesco Pugliese 1,
and
Giuseppe Pugliese 1 *
/GLUT1 axis in susceptibility vs resistance to diabetic glomerulopathy in the Milan rat model
2 Department of Clinical Sciences, ‘La Sapienza’ University, Rome, Italy; Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
3 Laboratory of Renal Immunopathology, San Carlo Borromeo Hospital, Milan, Italy
4 Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Giuseppe Pugliese, E-mail: giuseppe.pugliese{at}uniroma1.it
Abstract 
(TGF-) mRNA was significantly upregulated in diabetic vs nondiabetic MNS, but not MHS rats. Upon exposure to HG and/or TGF-, mesangial cells from 1- and 8-month-old MNS rats showed higher glucose transport activity and GLUT1 membrane expression than those from age-matched MHS rats. Likewise, ECM and TGF- production increased more markedly in response to HG and/or TGF- in MNS vs MHS mesangial cells., which may amplify ECM overproduction. Conversely, the haemodynamic protection from glomerulosclerosis in MHS rats is associated with lack of upregulation of TGF-s/GLUT1 axis, thus supporting the concept that this axis may represent the link between haemodynamic and metabolic mechanisms of injury..
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