Ameliorating effect of berbamine on hepatic key enzymes of carbohydrate metabolism in high-fat diet and streptozotocin induced type 2 diabetic rats
Graphical abstract
Introduction
Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemic results from the total absence or insufficient secretion/ action of insulin. Though the etiology is multifaceted, genetic predisposition associated with an intake of ill-balanced diet play a vital role in the incidence of diabetes. Sedentary lifestyle, increasing availability of energy dense food and lack of exercise have led to dramatic rise in type 2 diabetes mellitus (T2DM). It is estimated that a global prevalence of 382 million people with diabetes in 2013, is expected to double by 2035 [1].
Nutrition plays an important role in the development and also in the prevention of diabetes mellitus. A diet rich in fat can induce metabolic disorders like insulin resistance, dyslipidemia and hypertension in rodents and humans [2]. Administration of high fat diet and streptozotocin (HFD/STZ) to experimental animals lead to β-cell dysfunction, defective insulin function and persistent hyperglycemia that mimics the natural stages of progression of diabetes in humans [3]. An aberration in insulin action causes derangement in carbohydrate metabolism resulting from altered activities of enzymes that control glycolysis, gluconeogenesis in liver and muscle and produces hyperglycemia. Presently available oral hypoglycemic drugs have limitations and hence a search for newer drugs is warranted.
Medicinal plants and their bioactive constituents are commonly used worldwide to control diabetes and its complications due to their non-toxic nature, availability and affordability. Hence WHO has recommended the use of traditional plants for the treatment of chronic and life threatening diseases including diabetes mellitus. Berberis aristata is a well known medicinal plant whose fruits, stem, bark and root are used in ayurvedic preparations for their diverse medicinal properties. Berbamine (BBM) is a bis-benzylisoquinoline alkaloid derived from the roots of Berberis aristata, possess antioxidant, anti-inflammatory, immunomodulatory and cardiovascular effects [4,5]. However there was no study in the literature on the possible antidiabetic effects of BBM. In this context, the present study was designed to evaluate the effect of BBM on the activities of carbohydrate metabolic enzymes in HFD/STZ induced diabetic rats.
Section snippets
Chemicals and drugs
BBM and STZ were purchased from Sigma Aldrich Pvt. Ltd., (St. Louis, MO, USA). Insulin kit was purchased from Bioassay Technology Laboratory (Korain Biotech Co. Ltd, China). Diagnostic kits for glucose, hemoglobin (Hb) and glycated hemoglobin (HbA1c) were purchased from Agappe diagnostics Ltd, Kerala, India. All other chemicals used in this study were of analytical grade and obtained from SD fine and HIMEDIA, India.
Ethical statement for animal experimentation
Forty two male Sprague-dawley rats with body weight ranging from 160 to 180 g
Dose dependent effect of BBM on plasma glucose and insulin levels
An increase in plasma glucose with a significant decrease in insulin levels were observed in diabetic rats (Table 1). Oral administration of BBM at three different doses (50, 100 and 200 mg/kg b.w.) for 56 days resulted in significant improvement in plasma insulin with a fall in glucose levels at the end of the treatment period. There was no significant change in normal rats treated with BBM. The effect of BBM was compared with metformin, a standard drug.
Effect of BBM on changes in body weight, food and fluid intake of control and diabetic treated rats
Table 2 shows the changes in the body
Discussion
Type 2 diabetes mellitus is the most common metabolic disorder across the world and is becoming the major cause of morbidity and mortality in human populations. Intake of excess dietary fat blunts insulin mediated glucose utilization and promotes insulin resistance under diabetic conditions [17]. Further, administration of low dose of STZ (40 mg/kg b.w.) to HFD fed rats causes mild destruction of pancreatic β-cells by necrosis resulting in insulin deficiency [18]. Studies by Srinivasan et al. [
Conclusion
From the results of the present study, we conclude that administration of BBM dose dependently to diabetic rats improved insulin secretion and exhibited pancreatic β-cell protective activity. It ameliorated the activities of carbohydrate metabolic enzymes and restored glucose homeostasis in HFD/STZ induced diabetic rats. The molecular actions of BBM on improving insulin secretion and resistance are warranted.
Conflict of interest
The authors declare no conflict of interests.
Acknowledgement
The Indian Council of Medical Research (ICMR), New Delhi is gratefully acknowledged for the financial support in the form of Major Research Project. The authors gratefully thank UGC, DST for the financial support to the department.
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