Type II diabetes and obesity are two of the most prevalent metabolic disorders effecting a huge population throughout the world. Research over the last decade has unequivocally established considerable molecular links...Type II diabetes and obesity are two of the most prevalent metabolic disorders effecting a huge population throughout the world. Research over the last decade has unequivocally established considerable molecular links between them and hence they are often described in conjugation as ‘diabesity’. The hallmarks of type II diabetes are primarily reduced insulin sensitivity, progressive insulin resistance and consequent hyperinsulinemia.1 Whereas, hyperinsulinemia promotes a plethora of fat synthesis from excess circulating carbohydrate and hyperactive fat storage mechanisms, ultimately inducing hepatic steatosis, myosteatosis and pancreatic steatosis.1 This in turn, aggravates the insulin sensitivity further, inflicting more insulin resistance and even more hyperinsulinemia. Needless to mention that the vicious process in turn, promotes uncontrolled weight gain1 and many secondary metabolic disorders. The prevalent anti-diabetic and anti-obesity medications comes with several limitations ranging from inefficiency to adverse side effects.2 Here, we report an efficient strategy of repositioning previously approved drugs with novel indication in the context of diabesity by investigating deregulated signalling axes affecting patients with both the disorders. Our approach relies extensively on deciphering the strength of gene association in various interactomes, as it is known that within networks, genes linked to similar disease phenotypes tend to be functionally similar3 and remain proximal to each other.4 Moreover, the potential drug targets associated to a disease pathway also cluster proximal to the disease pathways.展开更多
基金supported by Start-up Research Grant(No.SRG/2019/000221)from Science&Engineering Research Board(SERB),Government of India to D.D.
文摘Type II diabetes and obesity are two of the most prevalent metabolic disorders effecting a huge population throughout the world. Research over the last decade has unequivocally established considerable molecular links between them and hence they are often described in conjugation as ‘diabesity’. The hallmarks of type II diabetes are primarily reduced insulin sensitivity, progressive insulin resistance and consequent hyperinsulinemia.1 Whereas, hyperinsulinemia promotes a plethora of fat synthesis from excess circulating carbohydrate and hyperactive fat storage mechanisms, ultimately inducing hepatic steatosis, myosteatosis and pancreatic steatosis.1 This in turn, aggravates the insulin sensitivity further, inflicting more insulin resistance and even more hyperinsulinemia. Needless to mention that the vicious process in turn, promotes uncontrolled weight gain1 and many secondary metabolic disorders. The prevalent anti-diabetic and anti-obesity medications comes with several limitations ranging from inefficiency to adverse side effects.2 Here, we report an efficient strategy of repositioning previously approved drugs with novel indication in the context of diabesity by investigating deregulated signalling axes affecting patients with both the disorders. Our approach relies extensively on deciphering the strength of gene association in various interactomes, as it is known that within networks, genes linked to similar disease phenotypes tend to be functionally similar3 and remain proximal to each other.4 Moreover, the potential drug targets associated to a disease pathway also cluster proximal to the disease pathways.
