The Caprine Casein-Alpha-S2 Protein Modulates the Molecular Mechanism 2 of Insulin Signal Transduction in Type2 Diabetes Rat

Fatchiyah Fatchiyah; Rista Nikmatu Rohmah; Lidwina Faraline Triprisila; Takeshi Ohta; Hazna Noor Meidinna

doi:10.18388/abp.2020_5357

Fatchiyah Fatchiyah 1) Research Center of Smart Molecule of Natural Genetics Resources, Brawijaya University 2) Biology Department, Faculty of Science, Brawijaya University https://orcid.org/0000-0001-6241-9665
Rista Nikmatu Rohmah 1Research Center of Smart Molecule of Natural Genetics Resource, Brawijaya University, Malang, East Java, Indonesia, 2) Biosains Institute, Brawijaya University, Malang, East Java, Indonesia https://orcid.org/0000-0002-2452-3020
Lidwina Faraline Triprisila 1)Research Center of Smart Molecule of Natural Genetics Resource, Brawijaya University, Malang, East Java, Indonesia, 2) Biosains Institute, Brawijaya University, Malang, East Java, Indonesia https://orcid.org/0000-0003-2266-7538
Takeshi Ohta 1)Research Center of Smart Molecule of Natural Genetics Resource, Brawijaya University, Malang, East Java, Indonesia, 2) Graduate School of Agriculture, Kyoto University, Kyoto, Japan https://orcid.org/0000-0002-9573-3455
Hazna Noor Meidinna 1)Research Center of Smart Molecule of Natural Genetics Resource, Brawijaya University, Malang, East Java, Indonesia, 2)DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), National Institute of Advanced Industrial Science and Technology (AIST), and Tsukuba Life Science Innovation, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan https://orcid.org/0000-0002-1550-9358

DOI: https://doi.org/10.18388/abp.2020_5357

Abstract

This study purpose was to investigate the association of casein-alpha-S2 protein of Caprine milk and molecular mechanismofinsulin signaltransduction in type2 diabetes mellitus (T2DM). The Caprine milk CSN1S2 protein treatment of 0, 375, 750, and 1500mg/kg BW were conducted to the control and T2DM rats. We observed several physiological parameters of all rats. The levels of insulin and TNF-α in the plasma were measured using ELISA.The expressions of proteins and mRNA levels of diabetes-related genes in the pancreas tissues were analyzed using Western Blotting and Real-Time PCR, respectively. Our study found that diabetic rats had lower body weight, food intake, and fecal weight compared with control rats. The Caprine milk CSN1S2 protein consumption affected the body weight of diabetic rats to increase, especially at the dose of 750mg/kg BW.Interestingly, the genes associated with insulin signaling were improved by the CSN1S2 protein treatment in diabetic rats, although their blood glucose and cholesterol level were not affected. The diabetic rats showed an elevated insulin level and GLUT4 protein expression after treatment. We also reported that the CSN1S2-treated diabetic rats had a gradually reduced expression of TNF-α and VCAM-1 in dose-dependent. Moreover, the 750mg/kg BW of CSN1S2 treatment enhanced the mRNA expressions of INS-receptor, GLUT4, IGF-1, CAMKK, and CAMKIV in diabetic rats. The ability of Caprine milk CSN1S2 protein to regulate the molecular mechanisms in the diabetes-signaling pathway indicated its potential therapeutic effects on diabetes management.