Indian Journal of Biochemistry & Biophysics Vol. 47, February 2010, pp. 44-48 Effect of metformin on renal microsomal proteins, lipid peroxidation and antioxidant status in dexamethasone-induced type-2 diabetic mice Rameshwar Jatwa* and Anand Kar School of Life Sciences, Devi Ahilya University, Takshashila Campus, Indore 452 017, Madhya Pradesh, India Received 26 October 2009; revised 08 December 2009 An SDS-PAGE analysis of renal microsomal fraction of albino mice was performed to study the involvement of proteins in dexamethasone-induced type-2 diabetes mellitus (DM) and their alterations by metformin, a widely accepted oral antidiabetic drug. In addition, changes in renal lipid peroxidation (LPO), activities of superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH) content, as well as renal somatic index (RSI) and daily rate of water consumption were also investigated. While dexamethasone administration (1.0 mg/kg for 21 days) expressed two renal proteins (43 kDa and 63.23 kDa), in addition to the increased fasting serum levels of glucose and insulin, renal LPO, RSI and daily rate of water consumption, a parallel decrease in renal SOD, CAT and GSH was also observed. Treatment with metformin normalized these alterations including the renal proteins and LPO, confirming its efficacy in ameliorating dexamethasone-induced type-2 DM and also the association of two proteins with type-2 DM. Keywords: Dexamethsone, Lipid peroxidation, Metformin, Mice, SDS-PAGE Diabetes mellitus (DM) is a disorder of carbohydrate, lipid and protein metabolism, caused either by lack in the secretion of insulin or loss of its function on target tissues 1 . It is primarily characterized by an inefficient utilization of circulating glucose, leading to consistent hyperglycemic condition 2 . The world health organization (WHO) recognized three main types of diabetes, viz. insulin-dependent DM (IDDM; type-1), non-insulin-dependent DM (NIDDM; type-2), and malnutrition-related DM (MRDM). Of these, type-2 comprises 85-90% of the total diabetic population. The etiology of type-2 DM, in which beta cells of pancreas are usually functional often involves hormonal imbalance 3,4 . The hormonal diabetes results from either due to the hypo or hyper functioning of other endocrine glands, most commonly pituitary, thyroid and adrenal 3,4 . Among these, the hormones of adrenal cortex are well known for their diabetogenic effects 4 . In the treatment of type-2 DM, several oral hypoglycemic agents, including that of biguanides and sulphonylureas are commonly used and among biguanides, metformin is considered as a drug of choice 5 . Earlier study has clearly indicated that in DM kidney tissues are invariably affected 6 . Also, increased rate of urinary protein excretion in diabetic subjects has been observed 7 . However, influence of hyperglycemia on renal protein profile in corticosteroid-induced type-2 diabetes has not been reported till date. In the present study, the alterations in the renal microsomal proteins expression and their possible reversal by an anti-diabetic drug metformin in dexamethasone-induced type-2 diabetic mouse model have been investigated. The changes in the concentrations of serum insulin and glucose, renal lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activities, glutathione (GSH) and protein contents, renal somatic index (RSI) and daily rate of water consumption have also been investigated to correlate with the altered hyperglycemic condition. _________ *Corresponding author: E-mail: rjatwa80@hotmail.com Phone: +917312477166; Fax: +917312360026 Abbreviations: APS, ammonium persulphate; CAT, catalase; DM, diabetes mellitus; DTNB, 5,5, dithiobis 2-trinitrobenzoic acid; GSH, glutathione; IDDM, insulin-dependent DM; LPO, lipid peroxidation; MDA, malondialdehyde; MRDM, malnutrition-related DM; NIDDM, non-insulin-dependent DM; RIA, radioimmunoassay; RSI, renal somatic index; SOD, superoxide dismutase; TBA, 2-thiobarbituric acid; TEMED, tetramethylenediamine.