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.

Hormonal Signaling Systems of the Brain in Diabetes Mellitus

“…Kumar et al, 2010). We showed that in the brain of rats with STZ-induced DM1, duration one month, as well as with neonatal model of DM2, duration 3 to 6 months, the sensitivity of AC to regulatory action of bromocriptine was decreased (Shpakov et al, 2006(Shpakov et al, , 2007a. The inhibitory effect of bromocriptine on forskolin-stimulated AC activity and its stimulating effect on GppNHp binding of G i proteins in synaptosomal membranes of diabetic rats were significantly decreased, predominantly in DM1.…”

Decreased Efferents of Mesencephalic Raphe Nuclei to Striatum in Animal Model of Streptozocin-Induced Diabetes

“…The MnR projections to ventral striatum are affected by diabetes mellitus more than that of those to dorsal striatum. Study of Shapakov and colleagues showed that the level of serotonin in striatum is not significantly different between diabetic and nondiabetic rats (21). On the other hand, some studies indicate that induction of diabetes mellitus causes a decrease in serotonin level of the striatum (22,23).…”

Molecular mechanisms for the effect of mastoparan on G proteins in tissues of vertebrates and invertebrates

“…The peptides corresponding to C-terminal regions 385-394 (α S -subunit) and 346-355 (α i2 -subunit) of human G proteins and polycationic peptides C-εAhx-WKK(C 10 )-KKK(C 10 )-KKKK(C 10 )-YKK(C 10 )-KK (peptide I) and (GRGDSGRKKRRQRRRPPQ) 2 -KεAhx-C(Acm) (peptide II) were synthesized as described previously [1][2][3][4]. eAhx, C 10 , and Acm are the residue of ε-aminohexanoic acid, residue of capric acid, and acetamide group, respectively.…”