INS and Insulin resistance: Loss of sensitivity to aspects of insulin action (insulin resistance) principally affects the liver, muscle, and adipose tissues and is selective for glucose and lipid metabolism, eg, sparing insulin's action to retain sodium in the distal tubule.4, 5 Reduction in insulin-mediated glucose disposal leads to compensatory hypersecretion of insulin to maintain homeostasis: Glucose intolerance ensues if this endocrine pancreas response is inadequate, although some obese individuals avoid T2D by virtue of a supranormal B-cell response.6