1)Dept of Biology Faculty of Sience, Brawijaya University
2)Central Lab. Of Life Sciences, Brawijaya University
The pathogenesis of NIDDM has been studied in various ethnic groups. It appears that insulin resistance can precede the clinical onset of NIDDM. Mutations of the human insulin receptor gene have been identified in patients with severe insulin resistance, and studies of these naturally occurring mutants may provide important insights into the relationship between structure and function of the receptor. The aim of our research is to characterize genomic and proteomic insulin receptor (hINSR) of Indonesian diabetes mellitus patients. The bloods were collected from normal and DM patients from some public clinics and Saiful Anwar Hospital, Malang. DNA and RNA were isolated from blood, and then sequenced by ABIPrims Sequencer. To find out the genomic hINSR, DNA sequences were analyzed and characterized by in silico analysis, such as alignment by BioEdit & BLAST program from NCBI, and superimposed by Strap JAVA program, 2D- & 3D-structure analysis Swiss Model program. To examine the cytoplasm pathway tyrosine kinase, using docking hINSR-Tyrosine Kinase domain & IRS-1 (PTB domain) analyzed by Hex 5.1. We found specific protein of DM patient from 2D-protein profile and some type mutation of hINSR and can change the INSR 3D-protein structure and the 3D ligand structure of hINSR and insulin completely changed on DM patient. According to our result, we suggested that the hINSR protein mutation of DM patient precede abnormally hINSR function against tyrosine kinase and perhaps correlated with genetic syndrome of insulin resistance. The change function is presumed to inhibit the interaction between hINSR and IRS, makes transduction signals disturbance in the process of absorption of glucose leads to insulin resistance of diabetes mellitus.
Key words: insulin receptor, diabetes mellitus, genetic syndrome, in silico, tyrosine kinase