Proinsulin C-peptide constricts glomerular afferent arterioles in diabetic mice. A potential renoprotective mechanism.
OBJECTIVE
an increased glomerular filtration rate (GFR) has been postulated as a potential mechanism involved in the progression of diabetic nephropathy. Studies suggest that C-peptide exerts a renoprotective effect on diabetes. The peptide decreases hyperfiltration in patients with type 1 diabetes, as well as in diabetic animal models. In this study, we investigated whether C-peptide causes a change in arteriolar diameter.


METHODS
C57-Bl mice were made diabetic by means of a single intravenous injection of alloxan 2 wk prior to the experiment. Age-matched normoglycemic mice served as controls. Afferent arterioles, intact with the glomeruli, were dissected and microperfused. The effect of luminal application of C-peptide, compared with scrambled C-peptide or vehicle, was investigated. The effect of the Rho-kinase inhibitor Y-27632 was also investigated.


RESULTS
C-peptide constricted afferent arterioles in diabetic mice by -27% compared with the control value. Normoglycemic arterioles administered C-peptide displayed a delayed and minute response (-4%). Scrambled C-peptide or vehicle administration, whether administered to hyperglycemic or normoglycemic mice, did not induce any effect. Addition of Y-27632 abolished the effect of C-peptide.


CONCLUSIONS
C-peptide induces constriction of afferent arterioles in diabetic mice. This can reduce enhanced GFR and may be one of the mechanisms in the renoprotective action of C-peptide in diabetes.
Nordquist
Lina
L
Department of Medical Cell Biology, Division of Physiology, University of Uppsala, Uppsala, Sweden.
Lai
En Yin
EY
Sjöquist
Mats
M
Patzak
Andreas
A
Persson
A Erik G
AE
D000577:Amides / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000033:anatomy & histology / Q000187:drug effects; D002096:C-Peptide / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012234:Rho Factor / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000577:Amides; D002096:C-Peptide; D004791:Enzyme Inhibitors; D011725:Pyridines; D012234:Rho Factor; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C108830:Y 27632; D011189:Potassium Chloride; D054460:rho-Associated Kinases; D020928:Mitogen-Activated Protein Kinases; D009638:Norepinephrine