TY - JOUR
T1 - Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat
T2 - A comparative study with metformin
AU - Khan, Sabbir
AU - Jena, Gopabandhu
N1 - Funding Information:
This work has been funded by National Institute of Pharmaceutical Education and Research , SAS Nagar, Punjab, India. The authors would also like to acknowledge MDC Pharmaceuticals Pvt. Ltd., Baddi, Himachal Pradesh, India for providing the generous gift of metformin hydrochloride. Further, authors would like to acknowledge Cayman Chemical Company, Michigan, USA for providing gift sample of HDAC fluorometric activity assay kit.
Publisher Copyright:
© 2016 Elsevier Ireland Ltd. All rights reserved.
PY - 2016/7/25
Y1 - 2016/7/25
N2 - Recent evidences highlighted that histone deacetylases (HDACs) can deacetylate the histone, various transcription factors and regulatory proteins, which directly or indirectly affect glucose metabolism. The present study aimed to evaluate the comparative effects of sodium butyrate (NaB) and metformin on the glucose homeostasis, insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet (HFD) and low dose streptozotocin (STZ, 35 mg/kg). NaB at the doses of 200 and 400 mg/kg twice daily as well as metformin (as a positive control) 150 mg/kg twice daily for 10 consecutive weeks were administered by i.p. and oral route, respectively. NaB treatment significantly reduced the plasma glucose, HbA1c, insulin-resistance, dyslipidemia and gluconeogenesis, which are comparable to metformin treatment. Further, NaB treatment ameliorated the micro- and macro-vesicular steatosis in liver and fat deposition in brown adipose tissue, white adipose tissue (adipocytes hypertrophy) as well as pancreatic beta-cell damage. In the present study, both NaB and metformin inhibited the diabetes-associated increased HDACs activity, thereby increased the acetylation of histone H3 in liver. The present findings demonstrated that NaB and metformin reduced insulin-resistance, dyslipidemia, fat accumulation and gluconeogenesis thereby improved the glucose homeostasis in rat. Thus, NaB might be a promising molecule for the prevention and treatment of type-2 diabetes and dyslipidemia.
AB - Recent evidences highlighted that histone deacetylases (HDACs) can deacetylate the histone, various transcription factors and regulatory proteins, which directly or indirectly affect glucose metabolism. The present study aimed to evaluate the comparative effects of sodium butyrate (NaB) and metformin on the glucose homeostasis, insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet (HFD) and low dose streptozotocin (STZ, 35 mg/kg). NaB at the doses of 200 and 400 mg/kg twice daily as well as metformin (as a positive control) 150 mg/kg twice daily for 10 consecutive weeks were administered by i.p. and oral route, respectively. NaB treatment significantly reduced the plasma glucose, HbA1c, insulin-resistance, dyslipidemia and gluconeogenesis, which are comparable to metformin treatment. Further, NaB treatment ameliorated the micro- and macro-vesicular steatosis in liver and fat deposition in brown adipose tissue, white adipose tissue (adipocytes hypertrophy) as well as pancreatic beta-cell damage. In the present study, both NaB and metformin inhibited the diabetes-associated increased HDACs activity, thereby increased the acetylation of histone H3 in liver. The present findings demonstrated that NaB and metformin reduced insulin-resistance, dyslipidemia, fat accumulation and gluconeogenesis thereby improved the glucose homeostasis in rat. Thus, NaB might be a promising molecule for the prevention and treatment of type-2 diabetes and dyslipidemia.
KW - Diabetes
KW - Fat accumulation
KW - Gluconeogenesis
KW - HDAC inhibitor
KW - Insulin-resistance
KW - Sodium butyrate
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U2 - 10.1016/j.cbi.2016.06.007
DO - 10.1016/j.cbi.2016.06.007
M3 - Article
C2 - 27270450
AN - SCOPUS:84974652543
SN - 0009-2797
VL - 254
SP - 124
EP - 134
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
ER -