No abstract

Carbohydrate metabolism markers, thyroid profile indexes, transaminase activity and structural features of liver were studied, taking into account sexual dimorphism, in rats which were keeping on a high-fructose diet under conditions of adequate iodine supply and pre- and postnatal iodine deficiency. It was found that under fructose loading of animals with iodine deficiency the risk of insulin resistance (IR) development increases (HOMA-IR index in insulin-resistant male rats under conditions of pre- and postnatal iodine deficiency increases respectively by 22 and 13% compared to the data in animals that received a high-carbohydrate diet and adequate iodine supply). It is important, that in males and females with IR, the secretion of free triiodothyronine decreased by 36 and 40%, thyroid-stimulating hormone – by 28 and 34%, respectively, compared to the data of intact animals. The development of IR was accompanied by the activation of aminotransferases in blood serum (more in males). In particular, in male rats with IR under conditions of pre- and postnatal iodine deficiency, the activity of aspartate aminotransferase increased by 2.7 and 2.4 times, alanine aminotransferase – by 3.9 and 2.7 times, respectively, which led to a decrease of the de-Ritis index (more significantly against the background of prenatal iodine deficiency – by 25%) in relation to the data in animals that were on a standard diet. The activity of aminotransferases in rats with IR under conditions of iodine deprivation was higher than in animals with isolated iodine deficiency – by 11-56% and IR – by 13-47 %. In animals with IR, the presence of binucleated hepatocytes with a diffuse decrease in the number of glycogen granules in them and accumulation of glycoproteins in the wall of liver vessels were found. The foci of fatty dystrophy and pronounced zonal character of dystrophic processes in hepatocytes were identified in females, diffuse dystrophy prevailed in males. In the cytoplasm of hepatocytes of animals with IR under conditions of prenatal iodine deficiency, the lightening and the granularity, single granules of glycogen were observed. Under these conditions, the average perimeter (by 74%) and area (by three times) of hepatocytes, the average area of nucleus (by 3.1 times), the average perimeter (by 50%) and area (by 66%) of the nucleolus were increased compared to the control values. The structural changes were consistent with an increase of the transaminase activity. Thus, fructose loading and the development of IR acts as a trigger for cytolysis of hepatocytes, which increases under conditions of iodine deficiency, especially prenatal.

Animals following a high-fructose diet during eight weeks, have experienced changes in metabolism and the signs of insulin resistance have developed. Under such conditions, moderate hyperglycemia, hyperinsulinemia, hyperuricemia, an increase of the level of glycosylated hemoglobin in whole blood were observed. The significant role of the HOMA-IR index, as an early marker of carbohydrate metabolism disorders at the stage of pre-diabetes, has been confirmed. In experimental animals against the background of the high-fructose diet, the changes in the lipid spectrum of the blood were revealed: an increase of the total cholesterol level, low-density lipoproteins, triglycerides against the background of a high-density lipoproteins decrease. These disorders and a significant increase of the atherogenicity reflect the development of secondary dyslipidemia. In this case, the disorders of carbohydrate metabolism were combined with the degree of dyslipidemia. Males were found to have at increased risk of development the insulin resistance and comorbid pathology. Iodine deficiency, especially of congenital nature, is an aggravating factor of metabolic disorders. The obtained data can serve as a basis for extend of preventive measures and identification of the priority treatment schemes for type 2 diabetes mellitus in residents of endemic regions.