scholarly journals Dapagliflozin Aggravates Renal Injury via Promoting Gluconeogenesis in db/db Mice

2018 ◽  
Vol 45 (5) ◽  
pp. 1747-1758 ◽  
Author(s):  
Yingli Jia ◽  
Jinzhao He ◽  
Liang Wang ◽  
Limin Su ◽  
Lei Lei ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Renal Impairment ◽  
Glucose Tolerance ◽  
Blood Urea Nitrogen ◽  
Urinary Glucose Excretion ◽  
Urea Nitrogen ◽  
Urinary Glucose ◽  
Glucose Excretion

Background/Aims: A sodium-glucose co-transporter-2 inhibitor dapagliflozin is widely used for lowering blood glucose and its usage is limited in type 2 diabetes mellitus patients with moderate renal impairment. As its effect on kidney function is discrepant and complicated, the aim of this study is to determine the effect of dapagliflozin on the progression of diabetic nephropathy and related mechanisms. Methods: Twelve-week-old male C57BL/6 wild-type and db/db mice were treated with vehicle or 1 mg/kg dapagliflozin for 12 weeks. Body weight, blood glucose, insulin tolerance, glucose tolerance, pyruvate tolerance and 24-hour urine were measured every 4 weeks. At 24 weeks of age, renal function was evaluated by blood urea nitrogen level, creatinine clearance, urine output, urinary albumin excretion, Periodic Acid-Schiff staining, Masson’s trichrome staining and electron microscopy. Changes in insulin signaling and gluconeogenic key regulatory enzymes were detected using Western blot analysis. Results: Dapagliflozin did not alleviate but instead aggravated diabetic nephropathy manifesting as increased levels of microalbuminuria, blood urea nitrogen, and glomerular and tubular damage in db/db mice. Despite adequate glycemic control by dapagliflozin, urinary glucose excretion increased after administration before 24 weeks of age and was likely associated with renal impairment. Increased urinary glucose excretion was mainly derived from the disturbance of glucose homeostasis with elevated hepatic and renal gluconeogenesis induced by dapagliflozin. Although it had no effect on insulin sensitivity and glucose tolerance, dapagliflozin further induced the expression of gluconeogenic key rate-limiting enzymes through increasing the expression levels of FoxO1 in the kidney and liver. Conclusion: These experimental results indicate that dapagliflozin aggravates diabetes mellitus-induced kidney injury, mostly through increasing gluconeogenesis.

Theaflavin Enriched Black Tea Extract Alleviates Diabetic Nephropathy by Suppressing Hyperglycaemia-Mediated Oxidative Stress and Inflammation in Streptozotocin-Induced Rats

2020 ◽  
Vol 10 ◽  
Author(s):  
Dhrubajyoti Sarkar ◽  
Sekhar Kumar Bose ◽  
Tania Chakraborty ◽  
Souvik Roy
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Blood Urea Nitrogen ◽  
Phenolic Content ◽  
Black Tea ◽  
Total Phenolic ◽  
Urea Nitrogen ◽  
Black Tea Extract ◽  
Tea Extract

Background: Diabetic nephropathy (DN), a microvascular complication of diabetes has been a significant health issue globally. However, theaflavin enriched black tea extract (BTE-TF) could restrain DN. Objective: The main objective of this exploration was to elucidate the effect of BTE-TF on DN, though the underlying mechanism remains unclear and requires further investigation. Method: The tea leaves were fermented to get black tea extract. Total phenolic content and HPLC were carried out to determine the phenolic content and theaflavin in the extract. Streptozotocin induced diabetic rats were treated with 100, 200, and 400 mg/kg/day BTE-TF extract for 12 weeks. Biochemical parameters like blood glucose, creatinine, blood urea nitrogen (BUN), triglyceride and antioxidant parameters of kidney tissue were measured. Histology, immunohistochemistry and TUNEL assay were performed to observe the effect of the extract with comparison to the standard drug (Metformin 200mg/kg/day). Result: Treated animals exhibited reduced blood glucose levels, blood urea nitrogen (BUN), creatinine, and serum triglycerides. Further, BTE-TF restored the histological alterations in the kidney. Chronic hyperglycaemia resulted in a significant increase in oxidative stress and pro-inflammatory cytokines of NF-kβ pathway. BTE-TF attenuated oxidative stress (p<0.01), inflammation (p<0.05) and apoptosis (p<0.05). Conclusion: This study suggests that BTE-TF exerts a protective role against diabetes-induced renal injury by ameliorating oxidative stress, inflammation, and apoptosis.

scholarly journals Clinical and genetic determinants of urinary glucose excretion in patients with diabetes mellitus

2020 ◽  
Author(s):  
Keisuke Monobe ◽  
Shinsuke Noso ◽  
Naru Babaya ◽  
Yoshihisa Hiromine ◽  
Yasunori Taketomo ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Genetic Determinants ◽  
Urinary Glucose Excretion ◽  
Urinary Glucose ◽  
Patients With Diabetes ◽  
Glucose Excretion

Effects of AVE2268, a Substituted Glycopyranoside, on Urinary Glucose Excretion and Blood Glucose in Mice and Rats

2011 ◽  
Vol 58 (11) ◽  
pp. 574-580 ◽  
Author(s):  
Martin Bickel ◽  
Harm Brummerhop ◽  
Wendelin Frick ◽  
Heiner Glombik ◽  
Andreas Herling ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Urinary Glucose Excretion ◽  
Urinary Glucose ◽  
Glucose Excretion

Antidiabetic and renoprotective effect of Anogeissus acuminata leaf extract on experimentally induced diabetic nephropathy

2018 ◽  
Vol 29 (4) ◽  
pp. 359-364 ◽  
Author(s):  
Archana M. Navale ◽  
Archana Paranjape
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Serum Creatinine ◽  
Blood Urea Nitrogen ◽  
Leaf Extract ◽  
Dependent Manner ◽  
Urinary Volume ◽  
Urea Nitrogen ◽  
Protein Excretion

Abstract Background Diabetic nephropathy is the leading cause of end-stage renal disease. Hyperglycemia, oxidative stress, and inflammation are some of the mechanisms involved in renal damage. Anogeissus acuminata (AA) is used in India as an antidiabetic agent and has potent antioxidant activity. However, it has never been evaluated for its effect on diabetic nephropathy. Hence, in the present study we aimed to evaluate its effect on streptozotocin-induced diabetes mellitus and its renal complications. Methods Diabetes mellitus was induced by injecting streptozotocin, 50 mg/kg, i.p. in rats fasted for 6 h. Rats with hyperglycemia were treated with extracts of AA for 8 weeks at doses of 100 and 300 mg/kg, orally. Human NPH insulin (4 IU/kg, s.c.) was used as standard treatment. Plasma glucose levels (at weeks 1, 2, 4, and 8) and oxidative stress parameters (at weeks 2 and 4) were assessed. Effect on diabetic nephropathy was evaluated by recording the urinary volume, urinary protein excretion, kidney weights, serum creatinine, and blood urea nitrogen levels at week 8. Results Methanolic extract of AA leaves produced statistically significant (p<0.05) hypoglycemic and antioxidant effect. It also resulted in improved urinary function, reflected by better urinary volume and reduced protein excretion in urine. AA treatment could prevent the elevation of serum creatinine and blood urea nitrogen level in a dose-dependent manner. Kidney hypertrophy could be attenuated remarkably, as reflected by the significantly lower kidney weight (KW) per 100 g body weight (p<0.05). Conclusions AA leaf extract attenuated the development of diabetic nephropathy and also demonstrated antidiabetic and antioxidant action.

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