Inhibition of sodium-linked glucose reabsorption in the kidney normalizes diabetes-induced glomerular hyperfiltration in conscious adenosine A1-receptor-deficient mice
2014 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 210, no 2, 440-445 p.Article in journal (Refereed) Published
Glomerular hyperfiltration is commonly observed in diabetics early after the onset of the disease and predicts the progression of nephropathy. In this study, we investigated the role of the increased tubular sodium/glucose co-transport for diabetes-induced glomerular hyperfiltration. To eliminate any potential confounding effect of the tubuloglomerular feedback mechanism (TGF), we used adenosine A1-receptor deficient (A1AR-/-) mice known to lack a functional TGF mechanism, and compared the results to corresponding wild-type animals (A1AR+/+). Diabetes was induced by an intravenous bolus injection of alloxan. Glomerular filtration rate (GFR) was determined in conscious mice by a single bolus injection of inulin. The sodium/glucose co-transporters were inhibited by phlorizin 30 minutes prior to GFR measurements. Normoglycemic animals had a similar GFR independent of genotype, and induction of diabetes resulted in similar glomerular hyperfiltration in both groups. Phlorizin had no effect on GFR in normoglycemic mice, whereas it reduced GFR in both genotypes during diabetes. Notably, the reduction was more pronounced in the A1AR-/-. This study demonstrates that increased tubular sodium/glucose reabsorption is important for diabetes-induced hyperfiltration, and that the TGF mechanism is not involved in these alterations, but rather functions to reduce any deviations from a new set-point.
Place, publisher, year, edition, pages
2014. Vol. 210, no 2, 440-445 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-113176DOI: 10.1111/apha.12152ISI: 000329519500020OAI: oai:DiVA.org:uu-113176DiVA: diva2:290076