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Iu A Pankov

Publications and source records attributed to Iu A Pankov.

At least 19 recordsLinked to original sources

[Adiponectin, a new hormone: its role in the pathogenesis of diabetes mellitus].

Adiponectin is a hormone of adipose tissue, activating lipid metabolism and other physiological functions. Adiponectin deficiency induces obesity and decreases insulin-regulated carbohydrate metabolism, thus leading to insulin resistance. Blood level of adiponectin falls in type 2 diabetes. Adiponectin receptors--AdipoR1 and AdipoR2--are proteins with 7 transmembrane domains, which are synthesized mostly in muscles and the liver and function in a close connection with G proteins. Obesity and diabetes lower the tissue concentration of the receptors, thus impeding adiponectin regulation of lipid exchange and lowering the effectiveness of the insulin control of carbohydrate exchange. Adiponectin also influences cardiovascular functions and prevents atherosclerosis and some of the other kinds of vascular pathology.

Adiponectin↗

[The role of leptin and its peptide mediators in neurophysiology].

The adipocyte hormone leptin binds to its receptors in hypothalamic neurons and decreases appetite and food consumption. Its effect on appetite is mediated by melanocortines (MC) that are derivative of proopiomelanocortin (POMK) and their receptor (MC4-R). The knock-out of POMC gene or MC4-R gene causes obesity in animals. However, the growth of the animals intensifies and their reproductive function does not cease. The paper covers consequences of mutations in genes responsible for leptin regulation of various functions.

Adipose Tissue↗

[Molecular and genetic study of the role of hormones, receptors, and enzymes in regulation of reproduction, lipid metabolism, and other human physiological functions].

Prevalence of uterine progesterone receptors over estrogen ones, high uterine cAMP level, and low uterine prostaglandin level are necessary conditions of normal pregnancy. In cases of spontaneous and antiprogestin RU486-induced abortions, estrogen receptors prevail over progesterone ones, cAMP level decreases, and prostaglandin concentration in decidual tissue increases. Porcine and bovine beta-lipotropines were the first proteins, whose correct amino acid sequence was first determined in Russia. Several research centers carried out collaborative studies of the nucleotide sequences of human and animal proopiomelanocortin (lipotropin precursor) and prolactin cDNA. Researchers constructed genetic engineering producers of human pre-proinsulin and somatostatin, identified structural genes expressed in pancreatic beta-cells, studied antigenic properties of glutamic acid decarboxylase (GAD), which determine insulin-dependent diabetes, and identified the cholesterase determinant. They revealed mutations in the genes of proopiomelanocortin and melanocortin receptors (MC4-P), which inhibit leptin regulation of appetite and are associated with human obesity.

Abortifacient Agents, Steroidal↗

[Study of the association between constitutional exogenous obesity and polymorphism of the apolipoprotein B gene].

An attempt was made to associate the insertion-deletion (Ins/Del) polymorphism of the apolipoprotein B gene (apoB) with obesity and to identify alleles and genotypes predisposing to this disorder. The apoB Ins/Del allele frequencies observed in the Russian population were similar to those in West European populations and significantly differed from frequencies reported for Asian populations. Patients with obesity did not differ from healthy individuals in allele and genotype frequencies regardless of whether total or sex-stratified samples were compared. Estimation of relative risk for individuals with genotype Ins/Ins did not reveal a significant association between obesity and this genotype. Thus, constitutional exogenous obesity did not prove to be associated with the Ins/Del polymorphism of the apoB gene in the Russian population.

Adolescent↗

[All human and animal organs, tissues and cells are endocrine].

All known hormones are shown to be synthesized and secreted by different structures of the brain and nervous system, including neurons and glial cells and many of them are neurotransmitters. It should be recognized that all the organs, tissues, and cells of animals and man are endocrine and secrete different hormones into the intercellular space and blood.

Animals↗

[Leptin--a peptide hormone from adipocytes. Sensation of the 23rd FEBS Meeting].

Studies of the obese gene are reviewed. Recessive mutations in the ob gene in homozygous state cause excessive weight and diabetes in mice. Cloning and expression of cDNA of the human and mouse ob genes revealed that the ob gene is only expressed in white adipose tissue. cDNA encodes the ob protein that consists of 167 amino acid residues, the homology between the mouse and human ob proteins being 84%. The peptide leptin, secreted into blood, consists of 145 amino acid residues and results from the cleavage of a signal peptide off the ob protein. Leptin was obtained by genetic engineering methods. Its injection into ob/ob mice decreases body weight and eliminates diabetes symptoms. Leptin also decreased body weight of healthy mice by activating the utilization of endogenous lipids in energy metabolism. Leptin was found in human and mouse blood and mouse adipose tissue but not in blood or adipose tissue of ob/ob mice. Based on the results obtained, it was postulated that leptin, a product of the ob gene, is a hormone that is secreted into blood in varying quantities by adipocytes and controls the adipose tissue weight by stimulating lipid metabolism in the organism.

Adipocytes↗

[ob protein--product of expressing an obesity gene and some aspects of modern-day endocrinology].

A brief review of the studies on the obese (ob) gene is given. The ob gene is a mouse gene, the mutations of which are associated with altered metabolism and increased lipid deposits in adipose tissue. Recessive ob gene mutations in homozygous mice result in obesity and diabetes mellitus. Both mouse and human ob cDNAs were cloned and sequenced using positional cloning, exon trapping, and PCR. Of ten tested tissues, the ob gene was expressed only in white adipose tissue. The ob gene cDNA has a region of the nucleotide sequence with an opening reading frame and encodes the ob protein consisting of 167 amino acid residues. Mouse and human ob proteins showed a 85% homology. The 145-amino acid peptide termed as leptin and derived from ob protein after cleavage of signal peptide is secreted in the blood and stimulates fat consumption in energy metabolism. The biologically active ob peptide has been obtained by gene engineering methods. Administration of the ob protein to ob/ob mice reduced body weight and abolished symptoms of diabetes. The ob protein lowered body weight also in healthy animals. It was biologically effective both upon parenteral and intravenous administration and also when injected into lateral ventricle of the brain. With a polyclonal antiserum against the peptide the ob protein was shown to be present in human and mouse plasma and mouse adipose tissue. Based on the data obtained, it is postulated that the ob gene protein product leptin, is a hormone, which is secreted by adipocytes in the blood in varying amounts and regulates the mass of adipose tissue by stimulating lipid metabolism. Similarly to adipocytes, many other organs and tissues are presumably endocrine and may secrete peptide hormones in the blood. This considerably extends the scope of endocrinology and makes it necessary to review the existing concepts and views.

Amino Acid Sequence↗

[Study on structural gene expression in human insulinoma].

A human insulinoma cDNA library was constructed in the expression plasmid vector pUEX1. The clone pUEX1Ins12 was selected by means of hybridization with an insulin probe. It codes for full size amino acid sequence preproinsulin. The bacterial strain pUEX3Ins8 producing proinsulin as beta-galactosidase fusion protein was obtained for the use of recombinant protein as an antigen in an ELISA to detect serum antibodies in subjects with IDDM. Recombinant clones containing the middle, N- and C-terminal domains of the GAD65, the major autoantigen in IDDM, were constructed in pVEX1. These clones may become important tools to study the nature of GAD autoreactivity in IDDM. The clone pHICEO.9 was selected from the human insulinoma cDNA library by immunoscreening with total human insulinoma protein antibodies. This clone expresses the C-terminal fragment of human cholesterol esterase/lipase containing its antigenic determinant and can be used for blood lipase determination. Four clones containing cDNA inserts (0.47-1.42 kb) without any significant homologies to the known sequences in the Gene Bank were obtained by means of statistic selection.

Amino Acid Sequence↗

[Genetic engineering in the bacterial synthesis of somatostatin].

Series of recombinant plasmids for expression of the synthetic gene somatostatin-14 (SST) as a fusion protein were obtained. The somatostatin gene was fused to chloramphenicol acetyltransferase (cat) or its deleted variant genes. Both parts of the resultant fusion protein were joined through a Met residue. The hybrid gene was expressed under the control of the cat gene promoter (Pcat), the tryptophan operon promoter (Ptrp) or the promoter of bacteriophage T5 (PT5). These fusions gave insoluble polypeptide products amounting from 5-10% of the total cellular protein under constitutive biosynthetic conditions (Pcat) to 5-30% upon induction (Ptrp, PT5). A correlation between the efficiency of expression and the length of cat, the power of the promoter used and the absence or presence of transcription terminators, was studied. The scheme for SST isolation from bacterial cells was developed. SST was liberated from the fused polypeptide by treatment with cyanogen bromide and purified to homogenity by a combination of chromatographic steps: gel filtration, ion-exchange and rpHPLC. The renaturated recombinant SST showed specific biological and immunological activities and had 98% purity. The yield was 1 mg of the purified cyclic SST/1 culture of E.coli.

Chloramphenicol O-Acetyltransferase↗

[Synthesis of somatostatin in Escherichia coli cells: isolation and characteristics].

A synthetic gene coding for somatostatin-14 (SST) was cloned in plasmid expression vectors in frame with the chloramphenicol acetyl transferase (CAT) gene, both genes being divided by a Met residue. The hybrid gene was expressed under the control of the CAT gene promoter (Pcat) or the tryptophan operon promoter (Ptrp). Them fused genes gave insoluble polypeptide products amounting from 5% of the total cellular protein under constitutive biosynthesis conditions (Pcat) to 30% upon induction (Ptrp). SST was liberated from the fused polypeptide by treatment with cyanogen bromide, purified to homogeneity by gel-filtration and reverse phase HPLC, and finally refolded by dilution and air oxidation. The renaturated recombinant SST showed the specific biological and immunological activities of the native peptide.

Amino Acid Sequence↗

[Effects of endogenous opioids on the development of reproductive function in rats].

The influence of opioid peptide on the process of formation of reproductive function in rats was studied. Administration of beta-endorphin to neonatal female rats did not affect the concentrations of oestrogen and androgen receptors in the hypothalamus and pituitary, whereas the content of testosterone receptors was significantly higher in both hypothalamus and pituitary. Chronic administration of beta-endorphin to both female and male rats does not affect the concentration of sex hormones. The results obtained indicate that chronic administration of beta-endorphin to neonatal female rats lead to formation of instable contacts in the mechanism of regulation of hypophysis gonadotropic function.

Animals↗

[The morphology of diabetic nephropathy in experimental diabetes induced by low doses of streptozotocin].

Kidneys of 16 Wistar rats were examined by light and electron microscopy, immunofluorescence and biochemically for the transamidinase activity at various periods of experimental diabetes induced by the fractionated intraperitoneal administration of low (40 mg/kg) doses of streptozotocin. 18 rats of the same age and sex served as control. This model of diabetes is characterized by a gradual decrease of the serum immunoreactive insulin, increase of hyperglycemia, the presence of "insulitis" 19 days after the beginning of the experiment and the development of nephropathy in the genesis of which immune mechanisms might participate. Transamidinase activity correlated with the alterations of renal tubuli. The conclusion is made on the possibility of using this model of experimental diabetes for studying the pathogenetic mechanisms of renal lesions in diabetes; transamidinase activity allows one to evaluate the nephron function in diabetic nephropathy.

Animals↗

[The role of beta-endorphin in regulating the conditioned reflex activity of cats].

The role of beta-endorphin in regulation of instrumental food conditioning and in more complicated forms of nervous activity in cats was found to involve a facilitating unspecific effect both on positive and negative food conditioning, the latter having a general adaptive character. The influence of the same small doses of beta-endorphin (10 mkg/kg - 15 x 10(-6) mkg/kg) on the choice responses was more complicated and depended on the basic level of conditioning and the typology of animals. Possible mechanism of the beta-endorphin effect on higher nervous activity, is discussed.

Animals↗

[Molecular biological aspects of the pathogenesis of diabetes mellitus].

The discovery of the key role played by the immune system in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) opens up new possibilities for its early diagnosis, at the stages preceding its clinical manifestation. Analysed are the markers of genetic susceptibility to IDDM associated with some major histocompatibility complex antigens (specifically with HLA-DR 3, HLA-DR4, and HLA-DQ), of the cellular and humoral anti-islet autoimmunity, as well as the origin of the islet-cell autoantigens. The markers' significance for the diagnosis and prognosis is discussed.

Diabetes Mellitus, Type 1↗

[The role of proteolytic processes in the stimulation of lipolysis in the adipose tissue by somatotropin, adrenocorticotropin and beta-lipotropin].

The influence of proteinase inhibitors on the lipotropic effect of somatotropic (STH), adrenocorticotropic (ACTH) and beta-lipotropic (LPH) hormones in adipose tissue was studied in vitro. The effect of STH was found to be completely dependent on the activity of tissue serine proteinases of trypsin and chymotrypsin types. The effect of LPH partly depended on serine proteinases of chymotrypsin type, whereas that of ACTH--on chymotrypsin and carboxylic proteinases. The effects of all the three hormones were also manifested during lysosomal proteolysis. The protease-dependent inhibition was specific for polypeptide hormones and was unobserved in the lipotropic effect of adrenaline. The inhibiting effect of serine proteinase inhibitors on hormones pretreated with blood plasma or proteinases was much weaker than on untreated hormones. In adipose tissue the early insulin-like effect of STH, unlike the late lipotropic effect, was independent of proteolysis. It was assumed that primary proteolysis plays a role in the activation of polypeptide hormones which is necessary for the manifestation of the lipotropic action.

Adipose Tissue↗