The exact mechanisms by which growth hormone (GH) damages the kidney inducing diabetic
nephropathy has not yet been elucidated. Recently, it has been shown that transferrin
has the same diabetogenic effects of GH, being its mediator. Transferrin was studied
using immunohistochemistry and immuno-electron microscopy in cases of early diabetic
nephropathy, and in controls. Transferrin was only found in diabetic cases in podocytes
and Bowman’s capsule cells, but also in the tubular cells of both diabetic and non-diabetic
controls. Immuno-electron microscopy for the presence of transferrin showed positive
signals in the cytoplasm of diabetic podocytes, but not in pedicels. This selective
deposition was associated with signs of organelle and cytoskeleton damage. On the
basis of previous evidence and present glomerular findings, these results suggest
an indirect diabetogenic effect on the kidney by GH mediated through transferrin.
Key words:
Growth Hormone - Transferrin - Podocyte - Diabetic Nephropathy
References
- 1
Chen N Y, Chen W Y, Kopchick J J.
A growth hormone antagonist protects mice against streptozotocin-induced glomerulosclerosis
even in the presence of elevated levels of glucose and glycated hemoglobin.
Endocrinology.
1996;
137
5163-5165
- 2
Vargas L, Kawada M E, Bazaes S, Karplus P A, Faerman C H.
Insulin antagonism: a novel role for human serum transferrin.
Horm Metab Res.
1998;
30
113-117
- 3
Vargas L, Kawada M E.
Adrenal and liver participation in the rat’s post-stress diabetic response.
Horm Metab Res.
1976;
8
383-388
- 4
Houssay B A, Rieti G.
Action diabetogene de l’extract antero hypophysaire.
CR Soc Biol, Paris.
1932;
11
479
- 5
Hansen A P.
Serum growth hormone patterns in juvenile diabetes.
Danish Medical Bulletin.
1972;
19 (Suppl. 1)
32
- 6
Matsubara M, Nakagawa K, Akikawa K.
Plasma transferrin levels in abnormal endocrine states. I. The changes in hypophysial
diseases before and after treatment.
Horm Metabol Res.
1988;
20
506-509
- 7
Taylor K W, Vargas L, Randle P J.
A pituitary-dependent inhibitor of glucose uptake by muscle in protein fractions of
human plasma.
Lancet.
1960;
1
1313-1315
- 8
Bernard A M, Ouled Amor A A, Goemare-Vanneste J, Antoine J L, Lauwerys R R, Lambert A,
Vandeleene B.
Microtransferinuria is a more sensitive indicator of early glomerular damage in diabetes
than microalbuminuria.
Clin Chem.
1988;
1
920-921
- 9
Hsu S M, Raine L, Fanger H.
Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison
between ABC and unlabelled (PAP) procedures.
J Histochem Cytochem.
1981;
29
557-580
- 10 Hyatt A D.
Immunogold labelling techniques. In: Electron microscopy in Biology. A practical approach. Harris JR (ed). Oxford,
New York, Tokyo; IRL Press 1991: 59-81
- 11
Kriz W, Gretz N, Lemley K V.
Progression of glomerular diseases: is the podocyte the culprit?.
Kidney Int.
1998;
54
687-697
- 12
Bruzzi I, Benigni A, Remuzzi G.
Role of increased glomerular protein traffic in the progression of renal failure.
Kidney Int.
1997;
5
29-S31
- 13
Kemp S F, Creech R G, Horn T R.
Glycosylated albumin and transferrin: short-term markers of blood glucose control.
J Pediatr.
1984;
105
394-398
- 14
McVerry B A, Fisher C, Hopp A, Huehns E R.
Production of pseudodiabetic renal glomerular changes in mice after repeated injections
of glycosylated proteins.
Lancet I.
1980;
1
738-740
- 15
Klahr S, Schrevier G, Ichikawa I.
The progression of renal disease.
N Engl J Med.
1988;
318
1657-1666
- 16
Pargtalunan M E, Miller P L, Jumping-Eagle S, Nelson R G, Myers B D, Rennke H G, Coplon N,
Sun L, Meyer T W.
Podocyte loss and progressive glomerular injury in type II diabetes.
J Clin Invest.
1997;
99
342-348
- 17
Mundel P, Kriz W.
Structure and function of podocytes: an update.
Anat Embryol.
1995;
192
385-397
- 18
Bradley S E, Wheeler H O.
On the diversities of structure, perfusion and function or the nephron population.
Am J Med.
1960;
24
692-697
- 19
Rizza R A, Lawrence J, Mandarino L, Gerich J E.
Effect of growth hormone on insulin action in man.
Diabetes.
1982;
31
683-689
- 20
Campos C A, Curutchet J L, Lanari A.
Papel del hígado en la hiperglucemia del lóbulo anterior de la hipófisis en el sapo.
Rev Soc Argent Biol.
1933;
9
11-15
- 21
Simard M, Manthos H, Giard A, Lefebure Y, Goodyer C G.
Ontogeny of growth hormone receptors in human tissues: an immunohistochemical study.
J Clin Endocrinol Metab.
1996;
81 (8)
3097-3102
- 22
Chen N Y, Chen W Y, Kopchnik J J.
Liver and kidney growth hormone (GH) receptors are regulated differently in diabetic
GH and GH antagonist transgenic mice.
Endocrinology.
1997;
138 (5)
1988-1994
- 23
Chen L, Boadle A, Harris D CH.
Toxicity of holotransferrin but not albumin in proximal tubule cells in primary culture.
J Am Soc Nephrol.
1998;
9
77-84
- 24
Alfrey A C, Fovent D H, Hammond W S.
Role of iron in tubule interstitial injury in nephrotoxic serum nephritis.
Kidney Int.
1989;
36
753-759
Dr. L. Vargas
Department of Cellular and Molecular Biology
Faculty of Biological Sciences
P. Universidad Católica de Chile
Casilla 114-D
Santiago 1
Chile
Email: E-mail:lvargas@genes.bio.puc.cl
