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Lithium reduces blood glucose levels, but aggravates albuminuria in BTBR-ob/ob mice

Glycogen synthase kinase 3 (GSK3) plays an important role in the development of diabetes mellitus and renal injury. GSK3 inhibition increases glucose uptake in insulin-insensitive muscle and adipose tissue, while it reduces albuminuria and glomerulosclerosis in acute kidney injury. The effect of chr...

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Autores principales: de Groot, Theun, Damen, Lars, Kosse, Leanne, Alsady, Mohammad, Doty, Rosalinda, Baumgarten, Ruben, Sheehan, Susan, van der Vlag, Johan, Korstanje, Ron, Deen, Peter M. T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731748/
https://www.ncbi.nlm.nih.gov/pubmed/29244860
http://dx.doi.org/10.1371/journal.pone.0189485
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author de Groot, Theun
Damen, Lars
Kosse, Leanne
Alsady, Mohammad
Doty, Rosalinda
Baumgarten, Ruben
Sheehan, Susan
van der Vlag, Johan
Korstanje, Ron
Deen, Peter M. T.
author_facet de Groot, Theun
Damen, Lars
Kosse, Leanne
Alsady, Mohammad
Doty, Rosalinda
Baumgarten, Ruben
Sheehan, Susan
van der Vlag, Johan
Korstanje, Ron
Deen, Peter M. T.
author_sort de Groot, Theun
collection PubMed
description Glycogen synthase kinase 3 (GSK3) plays an important role in the development of diabetes mellitus and renal injury. GSK3 inhibition increases glucose uptake in insulin-insensitive muscle and adipose tissue, while it reduces albuminuria and glomerulosclerosis in acute kidney injury. The effect of chronic GSK3 inhibition in diabetic nephropathy is not known. We tested the effect of lithium, the only clinical GSK3 inhibitor, on the development of diabetes mellitus and kidney injury in a mouse model of diabetic nephropathy. Twelve-week old female BTBR-ob/ob mice were treated for 12 weeks with 0, 10 and 40 mmol LiCl/kg after which the development of diabetes and diabetic nephropathy were analysed. In comparison to BTBR-WT mice, ob/ob mice demonstrated elevated bodyweight, increased blood glucose/insulin levels, urinary albumin and immunoglobulin G levels, glomerulosclerosis, reduced nephrin abundance and a damaged proximal tubule brush border. The lithium-10 and -40 diets did not affect body weight and resulted in blood lithium levels of respectively <0.25 mM and 0.48 mM. The Li-40 diet fully rescued the elevated non-fasting blood glucose levels. Importantly, glomerular filtration rate was not affected by lithium, while urine albumin and immunoglobulin G content were further elevated. While lithium did not worsen the glomerulosclerosis, proximal tubule function seemed affected by lithium, as urinary NGAL levels were significantly increased. These results demonstrate that lithium attenuates non-fasting blood glucose levels in diabetic mice, but aggravates urinary albumin and immunoglobulin G content, possibly resulting from proximal tubule dysfunction.
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spelling pubmed-57317482017-12-22 Lithium reduces blood glucose levels, but aggravates albuminuria in BTBR-ob/ob mice de Groot, Theun Damen, Lars Kosse, Leanne Alsady, Mohammad Doty, Rosalinda Baumgarten, Ruben Sheehan, Susan van der Vlag, Johan Korstanje, Ron Deen, Peter M. T. PLoS One Research Article Glycogen synthase kinase 3 (GSK3) plays an important role in the development of diabetes mellitus and renal injury. GSK3 inhibition increases glucose uptake in insulin-insensitive muscle and adipose tissue, while it reduces albuminuria and glomerulosclerosis in acute kidney injury. The effect of chronic GSK3 inhibition in diabetic nephropathy is not known. We tested the effect of lithium, the only clinical GSK3 inhibitor, on the development of diabetes mellitus and kidney injury in a mouse model of diabetic nephropathy. Twelve-week old female BTBR-ob/ob mice were treated for 12 weeks with 0, 10 and 40 mmol LiCl/kg after which the development of diabetes and diabetic nephropathy were analysed. In comparison to BTBR-WT mice, ob/ob mice demonstrated elevated bodyweight, increased blood glucose/insulin levels, urinary albumin and immunoglobulin G levels, glomerulosclerosis, reduced nephrin abundance and a damaged proximal tubule brush border. The lithium-10 and -40 diets did not affect body weight and resulted in blood lithium levels of respectively <0.25 mM and 0.48 mM. The Li-40 diet fully rescued the elevated non-fasting blood glucose levels. Importantly, glomerular filtration rate was not affected by lithium, while urine albumin and immunoglobulin G content were further elevated. While lithium did not worsen the glomerulosclerosis, proximal tubule function seemed affected by lithium, as urinary NGAL levels were significantly increased. These results demonstrate that lithium attenuates non-fasting blood glucose levels in diabetic mice, but aggravates urinary albumin and immunoglobulin G content, possibly resulting from proximal tubule dysfunction. Public Library of Science 2017-12-15 /pmc/articles/PMC5731748/ /pubmed/29244860 http://dx.doi.org/10.1371/journal.pone.0189485 Text en © 2017 de Groot et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
de Groot, Theun
Damen, Lars
Kosse, Leanne
Alsady, Mohammad
Doty, Rosalinda
Baumgarten, Ruben
Sheehan, Susan
van der Vlag, Johan
Korstanje, Ron
Deen, Peter M. T.
Lithium reduces blood glucose levels, but aggravates albuminuria in BTBR-ob/ob mice
title Lithium reduces blood glucose levels, but aggravates albuminuria in BTBR-ob/ob mice
title_full Lithium reduces blood glucose levels, but aggravates albuminuria in BTBR-ob/ob mice
title_fullStr Lithium reduces blood glucose levels, but aggravates albuminuria in BTBR-ob/ob mice
title_full_unstemmed Lithium reduces blood glucose levels, but aggravates albuminuria in BTBR-ob/ob mice
title_short Lithium reduces blood glucose levels, but aggravates albuminuria in BTBR-ob/ob mice
title_sort lithium reduces blood glucose levels, but aggravates albuminuria in btbr-ob/ob mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731748/
https://www.ncbi.nlm.nih.gov/pubmed/29244860
http://dx.doi.org/10.1371/journal.pone.0189485
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