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The C-peptide fragment EVARQ reduces glomerular hyperfiltration in streptozotocin-induced diabetic rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
2007 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 23, no 5, 400-405 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2007. Vol. 23, no 5, 400-405 p.
Keyword [en]
C-peptide, EVARQ, diabetes, glomerular filtration rate, kidney function, rats
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-104057DOI: 10.1002/dmrr.704ISI: 000248437400009PubMedID: 17103462OAI: oai:DiVA.org:uu-104057DiVA: diva2:219310
Available from: 2009-05-27 Created: 2009-05-27 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Novel Approaches to Treatment and Prevention of Diabetic Nephropathy
Open this publication in new window or tab >>Novel Approaches to Treatment and Prevention of Diabetic Nephropathy
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Several studies have reported beneficial effects of C-peptide supplementation in diabetic patients and animal models of insulinopenic diabetes. However, it is also established that good glycemic control is essential to minimize the risk of diabetes-induced complications. This thesis investigates potential mechanisms for the beneficial effect of C-peptide on glomerular hyperfiltration, and a novel, painless route of insulin administration.

The results demonstrate that both C-peptide and its C-terminal penta-peptide sequence reduce the diabetes-induced glomerular hyperfiltration within an hour. The results also indicate that C-peptide possibly reduces diabetes-induced hyperfiltration via three different mechanisms: 1. Constriction of the afferent arteriole was demonstrated on isolated vessels from diabetic mice. 2. A net dilation of the efferent arteriole was evident in vivo. 3. Inhibition of the Na+/K+-ATPase was demonstrated in vivo in diabetic rats as well as in vitro on isolated proximal tubular cells from diabetic rats. All these mechanisms are known regulators of the net glomerular filtration pressure.

The last part of this thesis demonstrates that intradermal administration with a newly developed patch-like microneedle device results in similar insulin concentration compared to standard subcutaneous delivery.

These findings provide an insight for the beneficial effects of C-peptide on diabetic kidney function, and shows that this effect can be achieved by infusion of the C-terminal penta-peptide sequence alone. This thesis also presents a novel, painless alternative to insulin injections that is controllable, requires minimal training, and therefore presents several advantages compared to current standard therapy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 76 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 290
Keyword
Physiology, Diabetes, Nephropathy, C-peptide, Microneedle, Renal, GFR, Oxygen Consumption, Reabsorption, Fysiologi
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-8308 (URN)978-91-554-7021-0 (ISBN)
Public defence
2007-12-07, Auditorium Minus, Gustavianum, Akademigatan 3, Uppsala, 13:15
Opponent
Supervisors
Available from: 2007-11-14 Created: 2007-11-14 Last updated: 2011-11-14Bibliographically approved

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