SnapShot: Physiology of Insulin Signaling

See online version for legend and references. systemic IR Apparently normal intrauterine growth and development, severe hyperglycemia and hyperke-tonemia, perinatal death as the result of diabetic ketoacidosis within 48–72 hours IRS-1 Retarded embryonal and postnatal growth, insulin resistance, normal fasting glycemia and normal or mild glucose intolerance, hyperinsulinemia IRS-2 Insulin resistance, impaired glucose tolerance, impaired insulin secretion, decreased β cell mass Brain IR Obesity, increased body fat mass, insulin resistance, hyperinsulinemia, hypertriglyceridemia, increased food intake (female only) IRS-2 Obesity, increased body fat mass, insulin resistance, impaired glucose tolerance, hyperinsulinemia, extended life span, more active and greater glucose oxidation, increased superoxide dismutase-2 in the hypothalamus Liver IR Normal body weight, severe insulin resistance, impaired glucose tolerance, hyperinsulinemia, increased hepatic glucose production IRS-1 Normal body weight, normal insulin sensitivity during fasting but insulin resistance after refeeding IRS-2 Normal body weight, normal insulin sensitivity after refeeding but insulin resistance during fasting IRS-1/IRS-2 Normal body weight, severe insulin resistance, severe glucose intolerance, marked hyperin-sulinemia skeletal muscle IR Normal body weight, normal insulin and glucose tolerance, increased epididymal fat pad, hypertriglyceridemia, increased FFA levels IRS-1 Normal body weight, normal insulin and glucose tolerance, decreased skeletal muscle mass IRS-2 Normal body weight, normal insulin and glucose tolerance, normal skeletal muscle mass IRS-1/IRS-2 Reduced body weight and body length, insulin resistance, normal glucose tolerance, reduced skeletal muscle mass, increased lactate levels Heart IR Normal body weight, normal insulin and glucose tolerance, decreased cardiac size and cardiac output, decreased fatty acid oxidation Kidney IR Normal body weight, normal insulin and glucose tolerance, albuminuria, histological features of diabetic nephropathy β cell IR Normal body weight, normal insulin tolerance, impaired glucose tolerance, impaired glucose-stimulated insulin secretion, decreased β cell mass IRS-2 Impaired glucose tolerance, impaired insulin secretion, decreased β cell mass Macrophage IR Normal body weight, normal insulin and glucose tolerance, protected from obesity-linked insulin resistance due to decreased hepatic glucose production and increased glucose disposal in skeletal muscle endothelial cell IR Normal body weight, normal insulin and glucose tolerance, reduced eNOS and endothelin-1 expression, insulin resistance on a low-salt diet IRS-1 Normal body weight, normal insulin and glucose tolerance, normal insulin signaling in endothelial cells IRS-2 Normal body weight, insulin resistance, impaired glucose tolerance, impaired insulin-induced eNOS phosphorylation, attenuation of insulin-induced capillary recruitment and insulin delivery associated with reduced glucose uptake by skeletal muscle IRS-1/IRS-2 Normal body weight, insulin resistance, impaired glucose tolerance, impaired insulin-induced eNOS phosphorylation in endothelial …