The C-peptide fragment EVARQ reduces glomerular hyperfiltration in streptozotocin-induced diabetic rats.
BACKGROUND
Initially, diabetes is commonly associated with an increased glomerular filtration rate (GFR), a potential mechanism involved in the progression of diabetic nephropathy. Several studies have reported reno-protective effects of C-peptide. C-peptide reduces diabetes-induced hyperfiltration, as well as renal hypertrophy and albuminuria. In order to gain further understanding of these effects, it is very important to localize the active sites within the C-peptide molecule. This study was designed to elucidate the effects of the C-peptide fragment EVARQ on kidney function, blood pressure and blood glucose levels in diabetic rats in vivo.


METHODS
The study was performed on adult inactin-anaesthetized male Sprague-Dawley rats. Two weeks prior to the experiment, diabetes was induced by a single intravenous injection of streptozotocin (55 mg/kg BW). After recovery and recording of baseline values, vehicle, C-peptide (50 pmol . kg BW(-1).h(-1)) or EVARQ (500 pmol.kg BW(-1).h(-1)) was continuously administered for a total of 100 min.


RESULTS
Before substance administration, all diabetic groups displayed a pronounced hyperfiltration as compared to the control rats. Continuous administration of both C-peptide and EVARQ reduced the diabetes-induced hyperfiltration within an hour. Furthermore, blood pressure was only reduced in diabetic rats that were given C-peptide, whereas the blood glucose decreased in the diabetic groups that were given either C-peptide or EVARQ.


CONCLUSIONS
The present study shows that administration of the C-peptide fragment EVARQ has similar effects on GFR and blood glucose levels as the intact C-peptide molecule, suggesting at least one active site within this region.
Nordquist
Lina
L
Department of Medical Cell Biology, Division of Integrative Physiology, Uppsala University, Uppsala, Sweden. Lina.Nordquist@mcb.uu.se
Moe
Erika
E
Sjöquist
Mats
M
D000818:Animals; D002096:C-Peptide / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use; D010446:Peptide Fragments / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002096:C-Peptide; D009842:Oligopeptides; D010446:Peptide Fragments