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Disturbance of transduction of adenylyl cyclase-inhibiting hormonal signaling in the myocardium and brain of rats with experimental type 2 diabetes

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Abstract

Presently, our work, as well as that of other authors, has produced convincing evidence in favor of the idea that disturbances in hormonal signaling systems are one of the main causes of the development of pathological alterations and complications in diabetes. However, the molecular mechanisms underlying these disturbances remain practically unstudied, particularly in insulin-independent type 2 diabetes. Using a neonatal streptozotocin model of type 2 diabetes, whose duration was either 80 or 180 days, we studied changes in the functional activity of components of the hormone-regulated adenylyl cyclase (AC) signaling system in the myocardium and brain striatum of diabetic rats as compared with control animals. In diabetes, the Gi-realized process of transduction of the hormonal signal inhibiting AC activity has been shown to be markedly impaired. This is manifested as a decrease of the inhibitory effect of hormones on AC activity and an attenuation of their stimulation of the G-protein’s GTP-binding activity. In the case of noradrenaline (myocardium), the inhibitory pathway of the AC system regulation is completely suppressed, while the stimulatory pathway is preserved. An increase in the duration of diabetes development from 80 to 180 days leads to some decrease in the transduction of hormonal signals realized via Gi-proteins. The stimulatory effects of biogenic amines and relaxin on AC activity and GTP binding in the myocardium and brain of diabetic rats change relatively little, both in the 80-and in the 180-day diabetes. Thus, in the experimental type 2 diabetes, disturbances in Gi-protein coupled signal cascades are primarily observed, through which hormones realize their inhibition of AC activity.

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Abbreviations

AR:

adrenergic receptor

AC:

adenylyl cyclase

AC:

system-adenylyl cyclase signaling system

STZ:

streptozotocin

Gs-and Gi-proteins:

heterotrimeric G-proteins of the stimulatory and inhibitory type

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    A. O. Shpakov, L. A. Kuznetsova, S. A. Plesneva & M. N. Pertseva

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  1. A. O. Shpakov
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  2. L. A. Kuznetsova
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  3. S. A. Plesneva
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  4. M. N. Pertseva
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Correspondence to A. O. Shpakov.

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Original Russian Text © A.O. Shpakov, L.A. Kuznetsova, S.A. Plesneva, M.N. Pertseva, 2007, published in Tsitologiya, Vol. 49, No. 4, 2007

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Shpakov, A.O., Kuznetsova, L.A., Plesneva, S.A. et al. Disturbance of transduction of adenylyl cyclase-inhibiting hormonal signaling in the myocardium and brain of rats with experimental type 2 diabetes. Cell Tiss. Biol. 1, 343–351 (2007). https://doi.org/10.1134/S1990519X07040062

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