THE ROLE OF ALTERATIONS IN THE BRAIN SIGNALING SYSTEMS REGULATED BY INSULIN,
IGF-1 AND LEPTIN IN THE TRANSITION OF IMPAIRED GLUCOSE TOLERANCE
TO OVERT TYPE 2 DIABETES MELLITUS
Shpakov A.O.
I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg;
e-mail: alex_shpakov@list.ru
One of the crucial factors leading to the development of pre-diabetes and type 2 diabetes mellitus (DM2)
are the disturbances in the brain hormonal signaling systems regulated by insulin, insulin-like growth factor-1
(IGF-1) and leptin. The causes of these disturbances are the changes in the redox balance and lipid metabolism
leading to lipotoxicity and endoplasmic reticulum stress in neuronal cells, as well as the dysfunctions in neurotransmitter
systems of the brain that are functionally associated with insulin, IGF-1 and leptin signaling systems.
The identification of molecular disturbances in insulin, IGF-1 and leptin systems of the brain in pre-diabetes
and DM2 can be used for early diagnostics of these diseases, and to develop new strategies for preventive
treatment of DM2 at the pre-diabetic stage. In the review, the literature data and the results of own investigations
concerning the changes in the insulin, IGF-1 and leptin systems of the brain in pre-diabetes and DM2
and their role in the etiology and pathogenesis of DM2 are analyzed, and the approaches to restore the functional
activity of these systems are discussed.
Key words: hypothalamus, insulin, insulin-like growth factor-1, leptin, brain, insulin receptor, diabetes
mellitus
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