Brain insulin: delivery routes, mechanisms of action, and application of intranasal insulin for the treatment of diabetes mellitus and metabolic syndrome

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Рұқсат ақылы немесе тек жазылушылар үшін

Аннотация

Insulin is traditionally considered a hormone of pancreatic origin that regulates glucose homeostasis and a wide range of metabolic and hormonal processes at the periphery. However, in recent decades, convincing evidence has been obtained that insulin also controls many processes in the brain, performing the functions of a neurotrophic factor, neuromodulator and neuroprotector, and some areas of the brain are capable of synthesizing insulin de novo. Insulin implements its effects in the central nervous system through the insulin signaling system, which in its structural and functional organization and regulatory mechanisms has significant similarities with that in the periphery. Since the total pool of insulin in the CNS consists of insulin produced by β-cells and entering the brain through the blood-brain barrier (BBB) and the hormone synthesized by brain structures, a decrease in its production or weakening of its transport through the BBB lead to insulin deficiency in the brain and disruption of its signaling. Other causes of weakened insulin signaling in the brain include central insulin resistance, neuroinflammation caused by increased activity of proinflammatory factors, the development of reactive astrogliosis and activation of microglia, as well as increased activity of enzymes that cause insulin degradation. One of the promising approaches for effective restoration of insulin signaling in the CNS is the use of intranasally administered insulin (IAI), which enters the brain directly through axonal pathways. Currently, IAI is used in the clinic to treat patients with Alzheimer's disease and cognitive deficit associated with type 2 diabetes mellitus (T2DM). However, the therapeutic potential of IAI is not limited to this. We have shown that IAI is effective in correcting metabolic and hormonal disorders associated with T1DM, T2DM, metabolic syndrome and obesity, and a number of its restorative effects are enhanced by the combined use of IAI with metformin, proinsulin C-peptide, and gangliosides, administered both systemically and intranasally. This indicates that the targets of IAI in diabetic pathology and obesity are not only brain structures, but also peripheral organs and tissues, including components of the gonadal and thyroid systems. This review is devoted to the problem of insulin signaling in the brain, its disorders in various pathologies, as well as the use of IAI to restore the activity of the brain's insulin system, including for the purpose of normalizing neurocognitive, metabolic and hormonal indicators in diabetic pathology.

Авторлар туралы

A. Shpakov

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: alex_shpakov@list.ru
St. Petersburg, 194223 Russia

K. Derkach

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: derkatch_k@list.ru
St. Petersburg, 194223 Russia

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