Gene Analysis and Docking for GCGR Gene involved in Non Insulin Dependent Diabetes Mellitus (NIDDM)

Author Name: *M. Salik Ansari
Author Email: ansarimsalik@gmail.com

Abstract

Diabetes mellitus is a disorder of carbohydrate metabolism characterized by impaired ability of the body to produce or respond to insulin and thereby maintain proper levels of sugar (glucose) in the blood Long since the disease was studied Insulin has gained lot of importance in the disease occurrence and treatment. However there are several other proteins that are yet not studied to the extent but are known to have an important role in the disease. Some of the proteins involved in Diabetes mellitus include BDNF, BCHE, GCGR etc., The current work was undertaken with an aim to analyze the GCGR gene (glucagon receptor). It is a G protein coupled receptor for glucagon hormone and plays a central role in the blood glucose regulation. The current work involves the Collection of the Diabetic blood samples and extraction of the DNA using Bunce Method. The Extracted DNA was purified and visualized in AGE. Primers were designed for the Amplification of the GCGE gene and the samples were sent for sequencing, which include both patient and Normal DNA samples. The sequences were than used for Multiple sequence alignment and the SNP regions in the Patient samples were identified. The work was extended to the Protein Analysis which included protein 3D structure Collection and developing a potential drug to inhibit the complications of Type II Diabetes. The chemicals were collected from the Pubchem database and were screened for several parameters like Drug likeliness, Ambiguity and Toxicity. All the selected chemicals were than used to dock with the 3D structure of the GCGR protein using the HEX Software. Based upon the energy values of the docking pairs the best docked ligand with lowest docking energy can be finalized.

Keywords

GCGR, SNP, Docking, Ambiguity, Drug likeliness, HEX, Multiple Sequence alignment.

Introduction

Diabetes is a major cause of morbidity and mortality, though these outcomes are not due to the immediate effects of the disorder. They are instead related to the diseases that develop as a result of chronic diabetes
mellitus. These include diseases of large blood vessels (macro vascular disease, including coronary heart disease and peripheral arterial disease) and small blood vessels (micro vascular disease, including retinal and renal vascular disease), as well as diseases of the nerves. Type II diabetes is far more common than type I diabetes, accounting for about 90 percent of all cases. The frequency of type II diabetes varies greatly within and between countries and is increasing throughout the world. Most patients with type II diabetes are adults, often older adults, but it can also occur in children and adolescents. There is a stronger genetic component to type II diabetes than to type I diabetes. For example, identical twins are much more likely to both develop type II diabetes than to both develop type I diabetes, and 7 to 14 percent of people whose mother or father has type II diabetes will also develop type II diabetes; this estimate increases to 45 percent if both parents are affected. In addition, it is estimated that about 40 percent of the Pima Indian population in Arizona has type II diabetes, whereas in the entire United States it is estimated that more than 10 percent of the population has type II diabetes.
Glucagon is a pancreatic hormone produced by cells in the islets of Langerhans. Glucagon is a 29-amino-acid peptide that is produced specifically by the alpha cells of the islets. It has a high degree of similarity with several glucagon-like peptides that are secreted by cells scattered throughout the gastrointestinal tract. Glucagon secretion is stimulated by the ingestion of protein, by low bloodglucose concentrations (hypoglycemia), and by exercise. It is inhibited by the ingestion of carbohydrates, an effect that may be mediated by the resultant increase in blood glucose concentrations and insulin secretion. Glucagon strongly opposes the action of insulin; it raises the concentration of glucose in the blood by promoting glycogenolysis, which is the breakdown of glycogen (the form in which glucose is stored in the liver), and by stimulating gluconeogenesis, which is the production of glucose from amino acids and glycerol in the liver. By increasing the concentration of glucose in the bloodstream, glucagon plays a critical role in maintaining blood glucose concentrations during fasting and exercise.

Conclusion

In the above work gene analysis of GCGR was performed after obtaining the sequence from the blood samples of the diseased patients. The sequence analysis was performed and the protein structure selected as the structure representative was 2L63. The structure was selected for docking. The chemical that was selected for the docking with the receptor was glucagon receptor antagonists-3. The docking was performed in HEX software an the docking energy obtained was -218.31. Thus indicates that the ligand can be best suited as the drug to act against the adverse effects of the disease Diabetes.

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