Adiponectin(additionally known as apM1, AdipoQ ,GBP-28and Acrp30) is a protein hormonewhich controls glucose levels and also unsaturated fat breakdown. In humans itis referred to by the ADIPOQ gene and is formed in fat tissue. Adiponectin is a244-amino-acid long polypeptide (protein).
There are four separate areas ofadiponectin. The first is a short signal sequence that targets the hormone for releaseoutside the cell; next is a short area that differs between species; the thirdis a 65-amino acid region with resemblance to collagenous proteins; the last isa globular domain. Adiponectin is a protein hormone that regulates variousmetabolic processes, including glucose regulation and unsaturated fatoxidation. Adiponectin is released from fat tissue (and furthermore from theplacenta during pregnancy) into the circulatory system and is extremely rich inplasma compared to numerous hormones.
Many studies have observed adiponectin tobe contrarily related with body mass index in patient populations. Adiponectin concentrationsrise during caloric limitation in animals and humans, for instance, in patientswith anorexia nervosa. AdiponectinDeficiency arises when there is low concentration of blood serum adiponectinlevels. This happens due downregulation of adiponectin and the reason for thisis not yet properly explained. The gene in affected people is usually found tobe localised to chromosome 3q27, a region known to affect the susceptibility toType 2 Diabetes and obesity.
The proper system of regulation of adiponectin is undetermined,however it could be managed by post-translational mechanisms in cells. A lowlevel of adiponectin is an autonomous risk factor for giving rise to: Metabolicdisorder , Diabetes mellitus . Lower levels of adiponectin are related withADHD in grown-ups. Adiponectin levels were observed to be elevated inrheumatoid joint inflammation patients reacting to DMARDs or TNF inhibitortreatment. Exercise induced production of adiponectin increased hippocampaldevelopment and prompted upper antidepressive symptoms in mice.The most commonlyused drugs used to treat adiponectin deficiency are Thiazolidinedione, whichare a class of heterocyclic compounds. Most of the drugs that belong to thisclass have been discontinued or banned due to their adverse side-effects thatdo more harm than good. Rivoglitazone belongs to this class ofthiazolidinedione and is currently undergoing research for use in the treatmentof type 2 diabetes.
If allowed by the FDA for commercialisation, it has thepotential of becoming a potent drug for the treatment of type 2 diabetes,obesity and other adiponectin deficiency related disorders. OBJECTIVESThe purpose ofthis research paper is to study the effect of gene mutations in the adipoq geneand hence its effect in the normal functioning of the body, particularlyobesity and type 2 diabetes. Out of the several protein constituents in theadipoq gene, the one which has been selected for further study is the R112Camino acid substitution. A successful study of mutation in the above statedgene will help us design drugs that could have therapeutic effects. Another purpose ofthis study is to evaluate the functioning of the drug Rivoglitazone against adiponectin deficiency, by comparing its functionto that of another known drug, Darglitazone , belonging to the same family. Apartfrom Rivoglitazone, another marine component derived drug is to be studied andcompared.
Expected Outcome The expectedoutcome of this study is to analyse and study the effects of gene mutation inthe adipoq gene and its consequent effect on the normal functioning of thehuman body. The efficacy of the drug Rivoglitazoneand the marine derived drug is also expected to be determined.