Glomerular hyperfiltration with hyperglycemia in the spontaneously diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model

Glomerular hyperfiltration is observed in an early stage of kidney diseases including diabetic nephropathy. A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we invest...

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Veröffentlicht in:Physiological research 2021-02, Vol.70 (1), p.45-54
Hauptverfasser: Sano, R, Ishii, Y, Yamanaka, M, Yasui, Y, Kemmochi, Y, Kuroki, F, Sugimoto, M, Fukuda, S, Sasase, T, Miyajima, K, Nakae, D, Ohta, T
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container_title Physiological research
container_volume 70
creator Sano, R
Ishii, Y
Yamanaka, M
Yasui, Y
Kemmochi, Y
Kuroki, F
Sugimoto, M
Fukuda, S
Sasase, T
Miyajima, K
Nakae, D
Ohta, T
description Glomerular hyperfiltration is observed in an early stage of kidney diseases including diabetic nephropathy. A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. Dapagliflozin achieved good glycemic control during the experimental period, inhibited the increase in GFR, and improved histopathological abnormalities in tubules. These results suggest that the SDT fatty rat is a useful model for analyzing the pathogenesis of diabetic nephropathy during its early stage and dapagliflozin improves not only hyperglycemia but also glomerular hyperfiltration and tubule lesions in SDT fatty rat.
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A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. 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A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. Dapagliflozin achieved good glycemic control during the experimental period, inhibited the increase in GFR, and improved histopathological abnormalities in tubules. These results suggest that the SDT fatty rat is a useful model for analyzing the pathogenesis of diabetic nephropathy during its early stage and dapagliflozin improves not only hyperglycemia but also glomerular hyperfiltration and tubule lesions in SDT fatty rat.</abstract><cop>Czech Republic</cop><pub>Institute of Physiology</pub><pmid>33453716</pmid><doi>10.33549/physiolres.934533</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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subjects Age
Animals
Benzhydryl Compounds - pharmacology
Cholesterol
Diabetes
Diabetes mellitus
Diabetes Mellitus, Experimental - drug therapy
Diabetes Mellitus, Experimental - genetics
Diabetes Mellitus, Experimental - physiopathology
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - pathology
Diabetes Mellitus, Type 2 - physiopathology
Diabetic Nephropathies - drug therapy
Diabetic Nephropathies - etiology
Diabetic nephropathy
Disease Models, Animal
Food
Glomerular Filtration Rate
Glucose
Glucosides - pharmacology
Hyperglycemia
Hyperglycemia - drug therapy
Hyperglycemia - pathology
Hypertrophy
Kidney diseases
Lesions
Male
Metabolism
Nephropathy
Obesity
Obesity - complications
Obesity - genetics
Pathogenesis
Rats
Rats, Sprague-Dawley
Sodium-glucose cotransporter
Sodium-Glucose Transporter 2 Inhibitors - pharmacology
Tubules
title Glomerular hyperfiltration with hyperglycemia in the spontaneously diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model
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