[Insulin resistance. Receptor and post-receptor abnormalities].
Insulin action starts with binding to a membrane receptor (insulin receptor-tyrosine kinase) and with activating an insulin receptor substrate 1 (IRS-1) and substrate 2 (IRS-2). Insulin receptors interact at least with three cascade reactions, phosphorylating G proteins and IRS-1, that activate PLC "ras" and PI-3-K. NIDDM can be defined as a disease caused by defective transduction of insulin signals and IR as a complex phenotype manifesting itself, emphasized by individual and environmental factors, in the cellular systems of signal transduction. IRS is a syndrome characterized by NIDDM, hypertension, visceral obesity, CHD: the X syndrome. Up to day the described mutations of the insulin-receptor gene are rare (e.g. the leprechaunism): genetic IR. Obesity is the principal cause of IR by receptorial and post-receptorial defects: metabolic IR. The obese skeletal muscle shows a reduction of insulin receptor and IRS-1 phosphorylation and of PI-3-K activation; the scarce expression of these proteins would determine the muscular IR. IR is a pattern of essential hypertension. Hypertension, dyslipidemia and abnormality of glucose metabolism are linked by IR. The so called high erythrocyte Na(+)-Li+ counter-transport is a new biochemical marker for IR and hypertension. These drugs can reduce IR: metformin, sulphonilureas, fibrats, dexfenfluramine, troglitazone, doxazosin, ACE-inhibitors.
Liguori
M
M
Servizio di Dietologia e Diabetologia, Ospedale Forlanini, Roma.
Urso
R
R
Fatigante
G
G
D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation; D009765:Obesity / Q000150:complications; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction
D007004:Hypoglycemic Agents; D007328:Insulin; D011972:Receptor, Insulin
Insulino-resistenza. Anomalie recettoriali e post-recettoriali.