Enhanced expressions of sodium–glucose cotransporters in the kidneys of diabetic Zucker rats

Tabatabai, Niloofar M.; Sharma, Mukut; Blumenthal, Samuel S.; Petering, David H.

doi:10.1016/j.diabres.2008.11.003

Cited by 91 publications

(64 citation statements)

References 18 publications

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“…В тканях почек мышей линии db/db (модель СД2) наблюдался больший уровень экспрессии SGLT2 в сравнении с гетерозиготным контролем db/+ [11]. Ана-логичные результаты получены в модели СД2 у крыс линии ZDF, где уровень экспрессии гена SGLT2 был по-вышен в 4,8 раза [12]. У мышей ob/ob не выявлено изме-нений синтеза SGLT2 в почках [13].…”

Section: роль Sglt2 в почечной реабсорбции глюкозы в норме и при сдunclassified

Empagliflozin: a new strategy for nephroprotection in diabetes

Korbut¹,

Климонтов²

2017

Diabetes mellitus

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Диагностика, контроль, лечение Diagnosis, control, treatment нгибиторы глюкозо-натриевого симпортера 2 (SGLT2) -новый класс сахароснижающих препаратов с многочисленными негликеми-ческими эффектами. Применение препаратов данного класса открывает большие перспективы не только в плане контроля гликемии, но и в профилактике осложне-ний сахарного диабета (СД). В данном обзоре обобщены результаты экспериментальных и клинических иссле-дований эффектов ингибитора SGLT2 эмпаглифлозина на структурно-функциональные изменения в почках при СД и динамику развития диабетической нефропа-тии (ДН). Поиск источников проведен в базах данных Medline/PubMed, Scopus, Web of Science, ClinicalTrials.gov, eLibrary. Представлены результаты оригинальных иссле-дований и мета-анализов, опубликованных преимуще-ственно в период 2012-2016 гг. Эмпаглифлозин

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Section: роль Sglt2 в почечной реабсорбции глюкозы в норме и при сдunclassified

Empagliflozin: a new strategy for nephroprotection in diabetes

Korbut¹,

Климонтов²

2017

Diabetes mellitus

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“…The renal cortex of streptozotocin (STZ)-diabetic rats was found to contain increased mRNA expression for SGLT1 and SGLT2 (164) and greater renal SGLT1 protein expression (165). Likewise, renal SGLT1 and SGLT2 mRNA levels in diabetic obese Zucker rats were higher than in age-matched lean rats (136). Primary cultures of human exfoliated proximal Fig.…”

Section: Hyperglycemia Enhances the Reabsorption Of Glucose In The Prmentioning

confidence: 99%

The proximal tubule in the pathophysiology of the diabetic kidney

Vallon

2011

American Journal of Physiology-Regulatory, Integrative and Comp

312

306

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Diabetic nephropathy is a leading cause of end-stage renal disease. A better understanding of the molecular mechanism involved in the early changes of the diabetic kidney may permit the development of new strategies to prevent diabetic nephropathy. This review focuses on the proximal tubule in the early diabetic kidney, particularly on its exposure and response to high glucose levels, albuminuria, and other factors in the diabetic glomerular filtrate, the hyperreabsorption of glucose, the unique molecular signature of the tubular growth phenotype, including aspects of senescence, and the resulting cellular and functional consequences. The latter includes the local release of proinflammatory chemokines and changes in proximal tubular salt and fluid reabsorption, which form the basis for the strong tubular control of glomerular filtration in the early diabetic kidney, including glomerular hyperfiltration and odd responses like the salt paradox. Importantly, these early proximal tubular changes can set the stage for oxidative stress, inflammation, hypoxia, and tubulointerstitial fibrosis, and thereby for the progression of diabetic renal disease.

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“…Normally, the SGLT2 transporter in the proximal tubule reabsorbs 90% of the filtered load of glucose. The expression of SGLT2 and glucose reabsorption in the proximal tubule are markedly elevated in diabetic animals, and upregulation of the reabsorption of the filtered load of glucose plays an important role in maintaining the hyperglycemic state (Vestri et al, 2001;Rahmoune et al, 2005;Tabatabai et al, 2009). Thus, selective SGLT2 inhibitors have been considered as potential new therapeutic targets for the treatment of diabetes.…”

Section: Introductionmentioning

confidence: 99%

Effects of a New SGLT2 Inhibitor, Luseogliflozin, on Diabetic Nephropathy in T2DN Rats

Kojima

Williams

Takahashi

et al. 2013

J Pharmacol Exp Ther

136

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This study examined the effect of long-term control of hyperglycemia with a new sodium glucose cotransporter 2 inhibitor, luseogliflozin, given alone or in combination with lisinopril on the progression of renal injury in the T2DN rat model of type 2 diabetic nephropathy. Chronic treatment with luseogliflozin (10 mg/kg/day) produced a sustained increase in glucose excretion and normalized blood glucose and glycosylated hemoglobin levels to the same level as seen in the rats treated with insulin. It had no effect on blood pressure. In contrast, lisinopril (10 mg/kg/day) reduced mean blood pressure from 140 to 113 mmHg. Combination therapy significantly reduced blood pressure more than that seen in the rats treated with lisinopril. T2DN rats treated with vehicle exhibited progressive proteinuria, a decline in glomerular filtration rate (GFR), focal glomerulosclerosis, renal fibrosis, and tubular necrosis. Control of hyperglycemia with luseogliflozin prevented the fall in GFR and reduced the degree of glomerular injury, renal fibrosis, and tubular necrosis. In contrast, control of hyperglycemia with insulin had no effect on the progression of renal disease in T2DN rats. Reducing blood pressure with lisinopril prevented the fall in GFR and reduced proteinuria and the degree of glomerular injury and tubular necrosis. Combination therapy reduced the degree of glomerular injury, renal fibrosis, and tubular necrosis to a greater extent than administration of either drug alone. These results suggest that control of hyperglycemia with luseogliflozin slows the progression of diabetic nephropathy more than that seen with insulin, and combination therapy is more renoprotective than administration of either compound alone.

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Enhanced expressions of sodium–glucose cotransporters in the kidneys of diabetic Zucker rats

Cited by 91 publications

References 18 publications

Empagliflozin: a new strategy for nephroprotection in diabetes

Empagliflozin: a new strategy for nephroprotection in diabetes

The proximal tubule in the pathophysiology of the diabetic kidney

Effects of a New SGLT2 Inhibitor, Luseogliflozin, on Diabetic Nephropathy in T2DN Rats

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