Аннотация:The system of glucose metabolism regulation is millions of years older than the insilin system and locomotor function. For this reason, the hypoglycemic activity of the hormone is mediated through fatty acid (FA) metabolism. Insulin blocks the ability of mitochondria to oxidize ketone bodies, short-, medium- and long-chain FA and makes them oxidize glucose, i.e. a physiologically unoptimal substrate. The relationship between FA and glucose in the Rnadle cycle is apparent only on the autocrine level (in the cell); they determine alternation of nutritive function (trophology) and biological exo/endo-reactions (after and without feeding respectively). Most antidiabetic medicines exhibit hypoglycemic activity, like insulin; they reduce the level of lipid substrates of oxidation in cytosol and mitochondria have to oxidize glucose. In these conditions, insulin increases glucose uptake by the cells mediated through GLUT4 transporters. Sulfonylurea derivatives enhance secretion of insulin by beta-cell. Biguanides covalently and irreversibly bind ketone bodies thereby preventing their oxidation by mitochondria. Fibrates, glitazones, flavonides, flavones, lipoic thio-FA, endogenous eicosanoids, derivatives of Ω-3 and Ω-6 essential polyenic FA, and conjugated unsaturated FA are agonists of peroxisome proliferator-activated receptors. They stimulate α-, β-, and Ω-oxidation of all exogenous a physiological FA and excessive palmitic saturated FA in peroxisomes which leads to cytosol hypolipidemia. Hypoglycemic preparations with the activity of oxidation beta-blockers arrest FA uptake by mitochondria. Hypoglycemic Ω-3 essential polyenoic FA activate GLUT4 function. Type 2 diabetes in middle-aged patients is a symptom of atherosclerosis, i.e. deficit of essential polyenoic FA caused by disturbed phospholipid synthesis and GLUT4 function. Diabetes should be in the first place considered as pathological FA metabolism and only in the second place as glucose pathology. This inference needs to be taken into account in the treatment of diabetes and in strategic programs of its prophylaxis.