title: Decrease in functional activity of G-proteins hormone-sensitive adenylate cyclase signaling system, during experimental type II diabetes mellitus.
abstract: The development of experimental type II diabetes mellitus in rats was accompanied by dysfunction of inhibitory and stimulatory heterotrimeric G-proteins, components of hormone-sensitive adenylate cyclase signal system. The function of inhibitory G-proteins decreased most significantly under these conditions, which is seen from weakened regulatory effects of somatostatin (in the myocardium) and bromocriptine (in the brain striatum) realized via inhibitory G-proteins in diabetic rats compared to controls. These hormones produce less pronounced inhibitory effect on forskolin-induced activation of adenylate cyclase. In the myocardium of diabetic rats, the stimulatory effects of isoproterenol and relaxin on adenylate cyclase realized via stimulatory G-proteins were decreased to a lesser extent. In the striatum of diabetic rats the stimulatory effect of serotonin and relaxin did not differ from the control. Therefore, dysfunction of stimulatory G-proteins during type II diabetes mellitus is characterized by tissue specificity. Synthetic peptides corresponding to functionally important regions in a-subunits of G-proteins and relaxin receptor LGR7 less effectively inhibited hormone signal transduction via the adenylate cyclase system in rats with type II diabetes. These changes reflect abnormal coupling between receptors and G-proteins in tissues of diabetic rats.
authors.affiliation: Laboratory of Molecular Endocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
authors.forename: A O
authors.initials: AO
authors.lastname: Shpakov
authors.forename: L A
authors.initials: LA
authors.lastname: Kuznetsova
authors.forename: S A
authors.initials: SA
authors.lastname: Plesneva
authors.forename: V M
authors.initials: VM
authors.lastname: Bondareva
authors.forename: I A
authors.initials: IA
authors.lastname: Guryanov
authors.forename: G P
authors.initials: GP
authors.lastname: Vlasov
authors.forename: M N
authors.initials: MN
authors.lastname: Pertseva
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012065:Relaxin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013004:Somatostatin / Q000494:pharmacology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D002316:Cardiotonic Agents; D006727:Hormone Antagonists; D006728:Hormones; D010455:Peptides; D018490:Serotonin Agents; D005576:Colforsin; D012701:Serotonin; D001971:Bromocriptine; D013004:Somatostatin; D012065:Relaxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol