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Objective: So far, high prevalence of metabolic symptoms accompanying diffuse idiopathic skeletal hyperostosis (DISH) appears not definitely elucidated because of their possible origin from other disorders such as diabetes and/or body mass differences. From such reasons this study was aimed to compare non-diabetic DISH patients to a group of age and BMI matched controls in order to distinguish the influence of DISH proper on metabolic parameters free of additional metabolic effects caused by diabetes and/or body weight differences., Methods: Both groups of patients were subjected to oral glucose tolerance test (OGTT) and fasting serum levels of glucose, insulin, C-peptide, growth hormone, insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGF-BP3) were assayed. Fasting serum total cholesterol, HDL cholesterol, triglycerides, non-esterified fatty acids (NEFA) and uric acid were determined as well. The indices of insulin sensitivity and insulin secretion were calculated., Results: With the exception of decreased NEFA serum level and decreased insulinogenic index and insulin/C-peptide ratio in DISH patients any other significant differences in serum parameters and indices of insulin sensitivity were not found., Conclusions: The data obtained suggest impaired beta-cell pancreatic stimulation and increased insulin hepatic extraction in DISH. It is assumed that the above mentioned conditions, if persisting for a long time, might lead to decreased ability of insulin to maintain normal serum glucose level and consequently to insulin resistance which is highly prevalent in symptomatic DISH patients.

In order to better understand the mechanisms leading to insulin resistance, the number of fat tissue insulin receptors, their affinity and insulin receptor protein in rats with monosodium glutamate-induced obesity were studied. Obese rats displayed significantly lower number of insulin receptors with high affinity. Surprisingly, the amount of insulin receptor protein was significantly elevated in these animals. The same relations have been already reported for angiotensin II binding and AT1 receptor protein in the same model of obesity. Therefore we suggest an existence of general defect of adipocyte cell membrane in monosodium glutamate-induced obesity characterized by the presence of high quantity of impaired receptor protein.

The explanation of the mechanism of the response to gravity changes is of great importance for the determination of the capacity of human subjects to adapt to the load of gravitational stress. Therefore several studies were performed to investigate the activity of endocrine system, since the hormones are involved in the regulation of physiological functions and metabolic processes. However the studies of endocrine system activity during altered gravity conditions, especially during the weightlessness are influenced by the several interventions in biomedical observations due to operational program of astronauts, wide variability in individual response and tolerance, use of extensive countermeasures, differences in the type of space missions and in the studies after landing also a hypergravity effect at landing and variability in postflight readaptation process. The significant changes of plasma insulin and glucose levels were observed in astronauts during space flights and in the first days of recovery period. In the first inflight period plasma insulin levels were increased, unchanged or decreased however after 4-5 weeks of exposure to weightlessness a decrease of insulin plasma levels were noted. After space flights an increase of plasma insulin levels were demonstrated in experimental animals and in human subjects. Since plasma insulin level is considered as most important factor involved in the regulation for insulin receptors in target tissues, an investigation of insulin receptors in various tissues was performed in rats exposed to space flight or to hypokinesia (model used for simulation of some effects of microgravity).

The binding of insulin (INS) and glucagon (GL) on isolated rat hepatocytes during the process of liver regeneration after partial hepatectomy was determined. Adult male rats were subjected to 65-70% partial hepatectomy, control animals were sham-operated. The binding of radioiodine labelled INS and GL to isolated hepatocytes was determined 1, 2, 3 and 5 days after the surgery. The plasma levels of INS and glucose and microviscosity of liver plasma membranes were also measured. The decrease of INS receptor binding capacity was found 1, 2, and 3 days after operation. No differences in sham and partially hepatectomized groups in INS binding were noted 5 days after operation. A single insulin injection during the process of regeneration did not affect these changes of INS binding to hepatocytes. The increase of GL binding was observed on the third day after partial hepatectomy, however, on the 5th day no changes of GL binding to its receptors were noted. The plasma insulin and glucose levels were similar in both hepatectomized and sham-operated rats. The increase of plasma membrane microviscosity of hepatocytes during the process of liver regeneration and a negative correlation between INS binding and membrane microviscosity were found. These results demonstrated significant changes in binding parameters of both INS and GL receptors in hepatocytes during liver regeneration induced by partial hepatectomy.

In searching for a genetic marker of type 2 diabetes we estimated the frequency of alleles of the Bgl II restriction fragment length polymorphism (RFLP) of the insulin receptor gene in a group of type II diabetic patients (n = 50), characterized by OGTT (glucose, insulin, C-peptide) and insulin receptor binding parameters. Leucocyte DNA was incubated with restriction endonuclease Bgl II and specific fragments were determined by Southern blot technique, using radioactive plasmid pINSR 13.1 as insulin receptor gene probe for hybridization. Insulin receptor numbers and receptor affinity were estimated by 125I-(Tyr-A-14)- insulin binding to red blood cells. Among control subjects the 20 kb fragment (allele Bgl II+) had a frequency of 0.21. In our group of diabetic patients this allele had a frequency of 0.10 (n.s., p greater than 0.05). In our study the insulin receptor genotype had no influence on body mass index, insulin and C-peptide during OGTT as well as insulin receptor binding data. So far, etiopathogenetic linkage between diabetes and insulin receptor variants (mutants) could unambiguously be proved in patients with extreme insulin resistance only. In our opinion, the estimation of the role of the gene as the reason underlying the disease inevitably requires the investigation of large families with multiple occurrence of type 2 diabetes.