A bovine milk-derived peptide ameliorates alloxan-injured pancreatic β cells through IRS2/PI3K/Akt signaling

Life Sci. 2022 Nov 1:308:120907. doi: 10.1016/j.lfs.2022.120907. Epub 2022 Aug 28.

Abstract

Background and aims: Lacto-ghrestatin is abovine milk-derived peptide with the sequence of LIVTQTMKG, named LGP9 here. This study aimed to investigate protective effects of LGP9 on diabetic β cells in vivo and in vitro.

Methods and results: Type-1-diabetic (T1D) mice were generated by alloxan (ALX; 50 mg/kg, i.v.) and received a four-week treatment schedule of LGP9 at 0.3 mg/kg and 1 mg/kg. Related biochemical parameters were analyzed, and the protein expression was evaluated by Western blotting. The results showed that LGP9 decreased body weight, water consumption and blood glucose, improved oxygen stress and upregulated IRS2/PI3K/Akt signaling in the pancreas of T1D mice. To further investigate the mechanism of LGP9 on the preventive effect of the pancreas, Rin-m5f cells were treated with 15 mM alloxan and followed with LGP9 at 30 μM and 90 μM. The results indicated that LGP9 rebalanced oxygen stress levels, increased cell proliferation, decreased cell apoptosis and activated IRS2/PI3K/Akt signaling.

Conclusion: LGP9 ameliorated alloxan-injured pancreatic β cells through IRS2/PI3K/Akt signaling. The finding provides important help for the research and development of LGP9 in therapeutics of diabetes.

Keywords: Akt; Alloxan; LGP9; PI3K; Type-1-diabetic mice.

MeSH terms

  • Alloxan
  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Type 1*
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin-Secreting Cells* / metabolism
  • Mice
  • Milk / metabolism
  • Oxygen / metabolism
  • Peptides / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Blood Glucose
  • Insulin Receptor Substrate Proteins
  • Irs2 protein, mouse
  • Peptides
  • Alloxan
  • Proto-Oncogene Proteins c-akt
  • Oxygen