THE DISTURBANCE OF THE TRANSDUCTION OF ADENYLYL CYCLASE INHIBITING HORMONAL SIGNAL IN MYOCARDIUM
AND BRAIN OF RATS WITH EXPERIMENTAL TYPE II DIABETES
A. O. Shpakov, L. A. Kuznetsova, S. A. Plesneva, M. N. Pertseva
I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg;
e-mail: alex_shpakov@list.ru
At present, the data obtained by us and other authors give evidence that disturbances in hormonal signaling
systems are the main causes of development of pathological changes and complications under the diabetes. However,
the molecular mechanisms of these disturbances remain obscure, especially in the case of insulin-independent
type II diabetes. Using neonatal streptozotocin model of 80- and 180-days type II diabetes the changes
in functional activity of hormone-regulated adenylyl cyclase (AC) signaling systems components in the myocardium
and the brain striatum of diabetic rats in comparison with the control animals were found. The transduction
of AC inhibitory hormonal signal meditated through Gi proteins was shown to by disturbed under diabetes. This
was manifested in both the decrease of hormone inhibitory effect on AC activity and weakening of hormone stimulation
of G-protein GTP-binding activity. In the case of noradrenaline (myocardium) the inhibitory pathway
of AC regulation by the hormone was vanished and the stimulation pathway, in contrary, was protected. Prolongation
of diabetes from 80 up to 180 days led to some weakening of Gi-protein-mediated hormonal signal transduction.
Stimulating effect of biogenic amines and relaxin on the AC activity and GTP-binding in the myocardium
and brain of diabetic rats were weakly changed in the case of both 80- and 180-days diabetes. To sum up, the
experimental type II diabetes caused disturbances mainly in Gi-coupled signaling cascades participating in hormone
inhibition of AC activity.
Key words: adenylyl cyclase, adenylyl cyclase signaling system, G-protein, diabetes, myocardium,
brain, relaxin, somatostatin
Back
Contents
Main
