insulin resistance

Think of insulin as someone knocking on a cell's door to ask it to take in sugar. In insulin resistance, the cell hears the knock but answers slowly and grudgingly, so the body has to send insulin to knock louder and longer to get the same response. The signal is no longer cheap — it takes more hormone to do the same job.

Insulin resistance is a reduced biological response of target tissues — chiefly muscle, liver, and fat — to a given concentration of insulin. At the molecular level it reflects impaired insulin-receptor signaling, so muscle and fat take up less glucose (via fewer GLUT4 transporters reaching the surface) and the liver fails to switch off gluconeogenesis. To compensate, beta cells secrete more insulin, producing a state of high insulin with normal or rising glucose.

It is the central defect of type 2 diabetes and a hallmark of metabolic syndrome and polycystic ovary syndrome, and is closely tied to visceral obesity, inactivity, and chronic low-grade inflammation. As long as the pancreas can keep up by oversecreting, blood glucose stays normal; diabetes appears only when beta-cell output can no longer outrun the resistance. Resistance can be measured with indices like HOMA-IR, though such estimates are imperfect.