New regulatory mechanism for insulin resistance and therapeutic target for age-related diabetes

Type 2 diabetes (T2D) is a chronic metabolic disorder affecting 370 million adults globally. In healthy individuals, the pancreas secretes insulin to control blood sugar levels after eating. In T2D patients, insulin-sensitive tissues like the liver and muscles do not respond to insulin, a condition known as insulin resistance. This results in prolonged high blood sugar, leading to complications such as limb loss, blindness, and death. The prevalence of T2D and insulin resistance increases with age, but the underlying mechanisms are unclear. The research team identified a crucial enzyme, membrane-type one matrix metalloproteinase (MT1-MMP), that regulates how ageing leads to insulin resistance in humans and monkeys.  

Insulin signals cells to remove sugar from the blood by binding with the Insulin Receptor (IR). Therefore, controlling the level of IR can affect insulin’s ability to regulate blood sugar levels and help modulate glucose homeostasis. The research team found that ageing process drives the activation of MT1-MMP systemically. Peripheral MT1-MMP directly sheds insulin receptors from the cell surface, blocking insulin from binding to these receptors and thus reducing insulin signalling.