INSULIN LIKE ANTIGEN: SOURCES OTHER THAN PANCREAS Review Article SAIMA KHURSHEED, RAZIQUE ANWER, TASNEEM FATMA Department of Biosciences, Jamia Millia Islamia University, New Delhi –110025, India. Email: fatma_cbl@yahoo.com * Received: 09 May 2012, Revised and Accepted: 21 June 2012 ABSTRACT Diabetes mellitus is the third largest cause of death after cardiovascular diseases and cancer. The failure to make insulin or insufficiency of insulin, is termed as diabetes mellitus. Insulin therapy is the only effective treatment of Type 1 diabetes mellitus. Insulin is a polypeptide key hormone which controls the level of the glucose in the blood and regulates the carbohydrate metabolism. In addition it also, metabolise fat and proteins and regulate expression of certain genes. Increased medicine’s cost; their pharmacological adverse effects and tremendous increase in diabetic population became a driving force in shifting interest towards development of bio- resource based medicines. Insulin was originally discovered in mammals, but later, insulin-related peptides were also recognized in plants. Insulin like antigen from plant with function, structure and sequence identical to vertebrate insulin are called ‘glucokinin’. Studies of our lab showing insulin-like antigens in Spirulina platensis S5 paved the path for in vivo study for anti-diabetic activity. Recently we reported ELISA based screening and western blot of Cyanobacterial strains using anti-human insulin antibody and showed that insulin like antigen was present in Spirulina platensis S5. 1,2 Keyword: Diabetes mellitus, Insulin like antigen, Herbal medicines, and Sulphonylureas. biguanides. This paved the path for confirmation of its antidiabetic activity in-vivo. INTRODUCTION Diabetes mellitus is associated with a large variety of complications and a greater risk of all manifestations of atherosclerosis. 3 Once diabetes develops, it is a costly disease to manage because of its chronic nature and severity of complications. 4 Worldwide estimates of its prevalence are expected to rise from 2.8% (171 million people) in 2000 to 4.4% (366 million people) in 2030. 5 Approximately 0.7% of the world’s population suffers from Type 1 diabetes mellitus; while about 90% of the diabetic world’s population suffers from Type 2 diabetes mellitus. 6 Type 1 [insulin dependent Diabetes mellitus (IDDM) or juvenile onset of diabetes] is caused by genetic disposition, environmental exposure to virus, toxin, stress, autoimmune reaction where beta cells of pancreas are destroyed by its own immunological system. Type 2 [Non insulin dependent Diabetes mellitus (NIDDM) or adult onset diabetes] is caused by insulin resistance: unable to utilize insulin produced because of cell receptor defect, insufficient production of insulin in response to blood glucose, excess production of glucose from the liver, genetic predisposition and obesity. The third type of diabetes is gestational diabetes mellitus (GDM) and is caused by insulin resistance due to pregnancy. Insulin is the primary medication in the treatment of Type 1 diabetes mellitus by directly promoting glucose uptake into muscle and fat cells as regulator of glucose metabolism and is a single hope for diabetic patients. Besides, controlling blood glucose level, insulin also stimulates cell proliferation. Insulin and insulin- like growth factors (IGFs) stimulate a signal transduction pathway that targets the protein synthesis apparatus by phosphorylating the S6 ribosomal protein (rp) on the 40 S ribosomal subunit. 7 7,8 Maize embryonic axis gradually reinitiates protein synthesis, based on translation of stored mRNAs and translation was shown highly regulated. 9,10 However, two other related proteins, insulin like growth factor (IGF-I) and IGF-II are more potent cell proliferators. 11 Because of greater antigenicity and impurity of animal insulin (bovine and porcine), genetically engineered human insulin was introduced in 1982 by Eli Lilly and Company. Unfortunately, diabetic patients, who received recombinant insulin for long periods developed antibodies to insulin. Developing fruits of Cowpea plant contained proteins of similar mass and amino acid sequence as bovine insulin. 12 Insulin is a small peptide hormone of about 6 KDa, Its highest concentration was found in the empty pods and seed coats, and not in the embryo, suggesting its involvement in carbohydrate metabolism in facilitating glucose transport across membranes, similar to its role in animals. Therefore, the search for more effective and safer hypoglycaemic agent started as an important area of active research. Plant based products may be one of the alternative for production of natural insulin. Insulin structure and function 13 composed of the A chain with 21 amino acids and the B chain with 30 amino acids, produced in vivo in the pancreatic cells (Fig. 1). Both chains are held together by two disulphide bonds between the cystines in CysA7 and CysB7 positions, CysA20 and CysB19 resp. Another disulphide bond is internal (intrachain disulfide bond) (A6 a A11). During insulin synthesis proinsulin is converted to insulin by cleavage of the binding peptide (C-peptide), binding the A and B chains together. Fig. 1: Structure of insulin. International Journal of Current Pharmaceutical Research ISSN- 0975-7066 Vol 4, Issue 3, 2012 A A c c a a d d e e m mi i c c S S c c i i e e n n c c e e s s