Effect of Statins Therapy in Diabetogenesis

Abstract

Statins are widely used in the management or inhibition of several processes that lead to the development of cardiovascular diseases. Increased statin therapy has been related to the induction of type II diabetes (DM), a state which predisposes to cardiovascular disease (CVD). Statins are well-known to possess anti-inflammatory properties and the ability to disrupt de novo biosynthesis of cholesterol and lipid homeostasis has been implicated in the induction of inflammatory responses within pancreatic β-cells. Inhibition of β-hydroxy β-methyl glutaryl-CoA (HMG-CoA) results an increased level of low-density lipoproteins (LDL) receptors. Increased LDL receptor numbers will replenish exhausted intracellular supplies, resulting in higher levels of intracellular cholesterol. Therefore, stimulating immunological response and inflammatory reactions, disrupt the functional integrity of the β-cell via oxidation of the plasma-derived low-density lipoprotein. Despite the pleiotropic effects of statins on the pancreatic β-cell, they have also been reported to affect a number of other cell types associated with the development of diabetes. Inhibition of the biosynthesis of isoprenoid by statins has been associated with the down-stream regulation of glucose transporter (GLUT 4) in adipose tissues, which facilitates the uptake of glucose. This effect resulted in increasing resistance to insulin in the liver, muscle, and adipose tissue. Adiponectin, a plasma protein released by adipocytes, alters fatty acids and carbohydrate metabolism both in the muscle cells and liver. This process indirectly influences resistance to insulin by the attendant decrease in hepatic gluconeogenesis and to upregulate muscular β-oxidation and glucose uptake.