The Proliferative Gene Cyclin D1 and Gluconeogenesis-Could Suppressing Glucose Production Also Promote Cancer?

摘要

Hepatic insulin resistance manifested as impaired suppression of glucose production is a key metabolic derangement that contributes to fasting hyperglycemia and increased HbA_(1c) levels in type 2 diabetes. Genetic manipulation to overexpress the key enzymes in gluconeogenesis (particularly PEPCK) in preclinical models has shown that a primary defect in this system can result in increased hepatic glucose production but, importantly, can lead to defects in insulin resistance in other tissues (muscle/fat) and impairments in insulin secretion. Despite this, medications that spedfically target hepatic glucose overproduction in diabetes are lacking. Currently, the only medication (other than insulin) that targets the liver is the biguanide metformin, and despite being used for more than half a century, the mechanism by which it does this is still not completely understood. Thus, understanding the mechanism causing hepatic insulin resistance will lead to more effective and targeted therapeutic options.