Hormonal Signaling Systems of the Brain in Diabetes Mellitus

Шпаков, А. О.; Chistyakova, O. V.; Derkach, K. V.; Бондарева, В. М.

doi:10.5772/28930

Cited by 11 publications

(12 citation statements)

References 151 publications

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“…One of the causes of these complications is the alterations in hormone-sensitive signaling systems, the adenylyl cyclase (AC) system in particular [3,4]. It was shown that changes in the functional activity of AC system in the heart, brain, and reproductive tissues in experimental T1DM were tissue and hormone speci�c [5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin

Шпаков

Derkach

Moyseyuk

et al. 2013

Dataset Papers in Pharmacology

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One of the causes of complications in type 1 diabetes mellitus (T1DM) is the changes in adenylyl cyclase (AC) signaling system, identi�ed on the early stages of the disease. However, the most signi�cant disturbances in this system occur on the later stages of T1DM, which ultimately leads to severe complications, but functional state of the AC system in late T1DM is poorly understood. e aim of this work was to study alterations in AC system sensitive to biogenic amines and polypeptide hormones in the heart, brain, and testes of male rats with long-term, 7-month, streptozotocin T1DM and to assess the in�uence on them of 135-day therapy with intranasal insulin. It was shown that AC effects of -adrenergic agonists in the heart, serotonin receptor agonists and PACAP-38 in the brain, chorionic gonadotropin and PACAP-38 in the testes, and somatostatin in all investigated tissues in long-term T1DM were drastically decreased. e treatment with intranasal insulin (0.48 IU/day) signi�cantly restored these effects. e results were obtained suggesting that long-term T1DM induces signi�cant alterations in hormone-sensitive AC system in the heart, brain, and testes that are much more pronounced, compared with short-term T1DM, and include a large number of hormonal regulations.

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Section: Introductionmentioning

confidence: 99%

Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin

Шпаков

Derkach

Moyseyuk

et al. 2013

Dataset Papers in Pharmacology

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“…Quite recently, the convincing evidences were obtained in favor of the fact that alterations in the signaling cascades regulated by hormones other than peptides of the insulin family, such as leptin, melanocortin, dopamine and serotonin, can also be causal factors leading to DM. First, it concerns the brain signaling systems and allows putting forward the concept of central genesis of DM [9][10][11]. In accordance with this conception, the abnormalities in hormonal signaling systems of the brain will trigger the mechanism leading to insulin resistance or insulin deficiency and, as a result, to the development of DM and its central and peripheral complications.…”

Section: Editorialmentioning

confidence: 99%

Alterations in Hormonal Signaling Systems in Diabetes Melitus: Origin, Causality and Specificity

Шпаков¹

2012

Endocrinol Metabol

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EditorialDiabetes Mellitus (DM) is a complex metabolic disease associated with many complications including hypertension, coronary heart diseases, atherosclerosis, retinopathy, nephropathy, reproductive and neurodegenerative disorders. A new view on the origin and pathogenesis of DM and its complications shared by many specialists nowadays has emerged from the study of changes in hormonal signaling systems in the tissues and organs of diabetic individuals. These changes occur not only in the signaling pathways regulated by insulin and IGF-1, the principal players responsible for development of DM and its central and peripheral complications, but also in the signaling systems regulated by a wide spectrum of other hormones and neurotransmitters, including leptin, biogenic amines, glutamate, purines, neuropeptides and glycoprotein pituitary hormones. It would be logical to suppose that alterations in these systems may be due to DM-induced changes in the expression, processing and functional activity of hormonal molecules, their cognate receptors and a majority of the downstream signal proteins, which finally leads to abnormalities in fundamental cellular processes, such as growth, differentiation, metabolism and apoptosis and contributes to triggering and development of pathological processes in the diabetic organs and tissues. However, there are many questions concerning the origin, causality and specificity of these alterations in DM and their role in the development of DM-induced complications, which are still unclear and controversial. The first to be solved are the folowing: (1) what is the causal relationship between the altered hormonal signaling and DM, (2) what is the role of the signaling system alterations in the compensatory mechanisms triggered by DM-induced metabolic and functional abnormalities, (3) what is the temporal and functional dynamics of these changes and in which conditions they are irreversible, (4) what is the interaction between the altered signaling cascades in DM and what is its mechanism, and how the changes in some individual cascades extend to the entire signaling network, (5) to which extent alterations in the signaling cascades are specific to the tissues and the cell types, as well as to certain hormones and signal cascades. There is no common view concerning these questions.It is generally accepted that a severe hyperglycemia and insulin deficiency in type 1 DM (T1DM), mild hyperglycemia and insulin resistance typical of type 2 DM (T2DM) and recurrent hypoglycemia as a result of inadequate insulin therapy are the major factors inducing the compensatory changes in hormonal signaling systems. These changes at the initial stage are reversible and can be completely restored with adequate therapy, usually by insulin treatment. With a prolonged action of the above pathogenetic factors the changes in hormonal systems are irreversible and fail to be restored with insulin therapy. This eventually leads to severe functional disturbances in CNS and peripheral tissues characteristic of the l...

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“…In the case of T2DM it is generally accepted that the main factors responsible for the neurodegenerative changes are the resistance of the peripheral tissues to insulin action, which leads to moderate hyperglycemia, and the recurrent hypoglycemia induced by inadequate insulin therapy and glycemic control [3]. Recently, many evidences have been obtained to the effect that the alterations and abnormalities of hormonal signaling systems regulated by insulin, insulin-like growth factor-1, leptin, biogenic amines, and peptide hormones controlling fundamental processes in the neuronal and glial cells contribute to triggering and development of neurodegenerative changes in the diabetic brain [4,5]. In our view, the changes in the brain signaling systems, on the one hand, may be due to formation of a compensatory response to physiological and biochemical dysfunctions occurring in DM, and, on the other hand, may themselves be the cause of these dysfunctions.…”

Section: Introductionmentioning

confidence: 99%

The Brain Adenylyl Cyclase Signaling System and Cognitive Functions in Rats with Neonatal Diabetes under the Influence of Intranasal Serotonin

Шпаков¹,

Derkach²

2012

J Metabolic Synd

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Hormonal Signaling Systems of the Brain in Diabetes Mellitus

Cited by 11 publications

References 151 publications

Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin

Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin

Alterations in Hormonal Signaling Systems in Diabetes Melitus: Origin, Causality and Specificity

The Brain Adenylyl Cyclase Signaling System and Cognitive Functions in Rats with Neonatal Diabetes under the Influence of Intranasal Serotonin

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