CHM-273S is a novel peptide derived from proprietary milk hydrolysate. It demonstrated the ability to induce IRS2 expression in primary murine fibroblasts. IRS2 is one of the main components of insulin receptor signaling pathway, and its expression activation is associated with the changes in the functioning of insulin- and glucose-dependent intracellular mechanisms in general. Such effect is typical for the main antidiabetic drugs including metformin and GLP-1R agonists and potentially indicates that CHM-273S can regulate cellular response to glucose and insulin. In the present work, we studied the ability of CHM-273S to alleviate symptoms of metabolic disorder caused by a high-sucrose diet (HSD) . Sprague-Dawley male rats (N=50) were given free access to 30% sucrose solution for 5 weeks. Animals with symptoms of a metabolic disorder - a stable significant increase in blood glucose concentration - were tested in the glucose tolerance test (GTT) . Single 1 mg/kg and 10 mg/kg CHM-273S i.p. administration 12, 2 and 0 hours prior to oral glucose injection in GTT significantly reduced blood glucose level. Additionally, CHM-273S administration 2 and 12 hours before blood sampling led to a decrease in fasting blood insulin concentration measured by ELISA and insulin resistance index HOMA-IR elevated as a result of HSD. These data indicates the peptide’s ability to alleviate the HSD-caused insulin resistance in experimental animals. Finally, the rats received CHM-273S and after 12 hours were injected with insulin 3 minutes before liver samples collection. CHM-273S restored pAKT (Thr308) and induced p-AKT (Ser473) levels in the liver, which indicates the ability of the peptide to normalize insulin signaling. The effect of CHM-273S on insulin signaling pathways in liver cells highly correlates with the observed decrease in blood glucose level in GTT and HOMA-IR values and could underly the mechanism of these effects.


V. Pavshintsev: None. N. Mitkin: None. I. Doronin: None. E. Emelianova: None. M. Lovat: None. G. Babkin: None. A. Malyshev: None.

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