Flavin associated Sulfhydryl oxidase and Ero1β in Insulin activity in Type 2 Diabetes Mellitus

Abstract

DM is proving to be a global public health burden as this number is expected to rise to another 200 million by 2040. Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycaemia. It may be due to impaired insulin secretion, resistance to peripheral actions of insulin, or both. Type 1 diabetes mellitus (T1DM) accounts for 5% to 10% of DM and is characterized by autoimmune destruction of insulin-producing beta cells in the islets of the pancreas. Type 2 diabetes mellitus (T2DM) accounts for around 90% of all cases of diabetes. In T2DM, the response to insulin is diminished, and this is defined as insulin resistance. During this state, insulin is ineffective and we now hypothesize that this ineffectiveness of Insulin is due to its improper folding affecting its activity. Insulin consists of two chains: A chain with 21 amino acids and B chain consists of 30 amino acids with intra and interchain disulphide bonds. These disulphide linkages help to stabilize the structure of insulin thus resulting in its proper biological activity. The flavoprotein quiescin-sulfhydryl oxidase (QSOX) rapidly inserts disulfide bonds into unfolded proteins thereby stabilising their tertiary and quaternary structures. As this enzyme is Flavin dependent, a dietary deficiency of Riboflavin leads to improper activity of Sulfhydryl oxidase resulting in abnormal folding of proteins affecting their biological activity. Riboflavin is one of the most common vitamin deficiencies seen in Indian population. The overall prevalence of deficiency of vitamin B2 (Riboflavin) was strikingly high as documented in various studies. Looking at the rising trend of Type 2 Diabetes Mellitus cases in worldwide and in India, it is always the need of time to look into the pathophysiology of Insulin inactivity in these cases. Sulfhydryl oxidase can be the target molecule and improving its actions with Riboflavin supplementation can prove to be an easy and cost-effective way for the target population to overall improve the Insulin activity. For this the biochemical link has to be established between Sulfhydryl oxidase, Riboflavin and Insulin. Hence, this study aims establish the mechanistic link between serum Sulfhydryl oxidase and Ero1β with serum Riboflavin and Insulin in Type 2 Diabetes Mellitus patients.