Functional defects in adenylyl cyclase signaling mechanisms of insulin and relaxin in skeletal muscles of rat with streptozotocin type 1 diabetes |
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Authors: | Alexander O Shpakov Ludmila A Kuznetsova Svetlana A Plesneva Alexander P Kolychev Vera M Bondareva Oksana V Chistyakova Marianna M Pertseva |
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Institution: | (1) Russian Academy of Sciences, Sechenov Institute of Evolutionary Physiology and Biochemistry, 194223 St. Petersburg, Russia |
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Abstract: | Functional disturbance in the novel adenylyl cyclase signaling mechanism (ACSM) of insulin and relaxin action in rat streptozotocin
(STZ) type I diabetes was studied on the basis of the authors’ conception of molecular defects in hormonal signaling systems
as the main causes of endocrine diseases. Studying the functional state of molecular components of the ACSM and the mechanism
as a whole, the following changes were found in the skeletal muscles of diabetic rats compared with control animals: 1) increase
of insulin receptor binding due to an increase in the number of insulin binding sites with high and low affinity; 2) increase
of the basal adenylyl cyclase (AC) activity and the reduction of AC-activating effect of non-hormonal agents (guanine nucleotides,
sodium fluoride, forskolin); 3) reduction of ACSM response to stimulatory action of insulin and relaxin; 4) decrease of the
insulin-activating effect on the key enzymes of carbohydrate metabolism, glycogen synthase and glucose-6-phosphate dehydrogenase.
Hence, the functional activity of GTP-binding protein of stimulatory type, AC and their functional coupling are decreased
during experimental type 1 diabetes that leads to the impairment of the transduction of insulin and relaxin signals via ACSM. |
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Keywords: | Adenylyl cyclase signaling insulin relaxin biogenic amine rat skeletal muscle type 1 diabetes streptozotocin |
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