Promising Directions for Regulating Signaling Pathways Involved in the Type 2 Diabetes Mellitus Development

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Abstract

Many studies confirm that substances of natural origin have a pronounced affinity for type 2 diabetes mellitus (T2DM) therapeutic targets. At the moment, there is growing interest in bioactive peptides, phytochemicals, and drugs from other natural sources as highly effective, safe and promising antidiabetic agents. Natural sources are a promising resource for regulating several pathological pathways in T2DM. The review describes ways to mitigate insulin resistance and tissue sensitivity to glucose through PTP1β (protein tyrosine phosphatase 1β), GLP-1R (glucagon-like peptide receptor), DPP-4 (dipeptidyl peptidase-4), AMPK (adenosine monophosphate activated protein kinase), MAPK (mitogen-activated protein kinase). Regulation of obesity and oxidative stress development through CCN3 (nephroblastoma overexpressed gene), PPAR-γ (peroxisome proliferator-activated receptor γ), Nrf2 (nuclear factor erythroid-related factor 2), FFAR (free fatty acid receptors), 11β-HSD1 (11β-hydroxysteroid dehydrogenase). Regulation of hyperglycemia through alpha-amylase inhibitors, regulation of glucose metabolism through GFAT (glutamine fructose-6-phosphate aminotransferase), FOXO1 (forkhead box protein O1), GLUT4 (glucose transporter type 4), PGC-1α (receptor gamma coactivator 1α activating peroxisome proliferator). The review examines the use of natural sources, from which low-molecular-weight and peptide compounds are used as T2DM targets modulators.

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About the authors

N. A. Borozdina

Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Branch of the Russian Biotechnological University (ROSBIOTECH)

Author for correspondence.
Email: borozdina@bibch.ru
Russian Federation, prosp. Nauki 6, Pushchino, 142290; prosp. Nauki 3, Pushchino, 142290

D. V. Popkova

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences

Email: borozdina@bibch.ru
Russian Federation, prosp. 100 let Vladivostoku 159, Vladivostok, 690022

I. A. Dyachenko

Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Branch of the Russian Biotechnological University (ROSBIOTECH)

Email: borozdina@bibch.ru
Russian Federation, prosp. Nauki 6, Pushchino, 142290; prosp. Nauki 3, Pushchino, 142290

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2. Fig. 1. Pathways for regulating insulin resistance, fat and glucose metabolism in type 2 diabetes. Promising methods for regulating insulin resistance include inhibition of 11β-HSD1, p38 MAPK, PTP1B, DPP-4, and activation of IRS1 and GLP-1R. Translocation of GLUT4 to the membrane surface helps reduce insulin resistance. Activation of AMPK and PGC-1α, increase in GLP-1 and GIP, and decrease in FFAR expression are proposed to activate FFA oxidation and reduce oxidative stress.

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3. Fig. 2. Effect of α-amylase inhibitors in T2DM. α-amylase inhibitors not only reduce peak glucose concentration during meals, but also trigger mechanisms regulating insulin resistance and FFA metabolism through GLP-1 secretion, as well as directly through the prevention of hyperglycemia.

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