Pancreastatin inhibitor, PSTi8 ameliorates metabolic health by modulating AKT/GSK-3β and PKCλ/ζ/SREBP1c pathways in high fat diet induced insulin resistance in peri-/post-menopausal rats.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Inc Country of Publication: United States NLM ID: 8008690 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5169 (Electronic) Linking ISSN: 01969781 NLM ISO Abbreviation: Peptides Subsets: MEDLINE
    • Publication Information:
      Publication: New York, NY : Elsevier Science Inc.
      Original Publication: Fayetteville, N. Y., Ankho International.
    • Subject Terms:
      Insulin Resistance*; Chromogranin A/*antagonists & inhibitors ; Dietary Fats/*pharmacology ; Glycogen Synthase Kinase 3 beta/*metabolism ; Isoenzymes/*metabolism ; Molecular Chaperones/*metabolism ; Peptides/*pharmacology ; Postmenopause/*metabolism ; Protein Kinase C/*metabolism ; Proto-Oncogene Proteins c-akt/*metabolism ; Sterol Regulatory Element Binding Protein 1/*metabolism; Animals ; Chromogranin A/metabolism ; Female ; Humans ; Rats
    • Abstract:
      Increase in the prevalence of insulin resistance (IR) in peri-/post-menopause women is mainly due to hormone deficiency and lifestyle. PSTi8 (PEGKGEQEHSQQKEEEEEMAV-amide) is a pancreastatin inhibitor peptide which showed potent antidiabetic activity in genetic and lifestyle induced type 2 diabetic mice. In the present work, we have investigated the antidiabetic activity of PSTi8 in rat models of peri-/post-menopausal IR. 4-vinylcyclohexenediepoxide treated and ovariectomized rats were fed with high fat diet for 12 weeks to develop the peri-/post-menopausal IR. PSTi8 peptide was administered after the development of peri-/post-menopausal IR rats. PSTi8 (1 mg/kg, i.p) improved the glucose homeostasis which is characterized by elevated glycogenesis, enhanced glycolysis and reduced gluconeogenesis. PSTi8 suppressed palmitate- and PST- induced IR in HepG2 cells. PSTi8 treatment enhanced energy expenditure in peri-/post-menopausal IR rats. PSTi8 treatment increased insulin sensitivity in peri-/post-menopausal IR rats, may be mediated by modulating IRS1-2-phosphatidylinositol-3-kinase-AKT-GSK3β and IRS1-2-phosphatidylinositol-3-kinase-PKCλ/ζ-SREBP1c signaling pathways in the liver. PSTi8 can act as a potential therapeutic peptide for the treatment of peri-/post-menopausal IR.
      (Copyright © 2019 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Diabetes; Estrogen deficiency; Insulin resistance; PSTi8; Pancreastatin inhibitor; peri-/post-menopause
    • Accession Number:
      0 (Chromogranin A)
      0 (Dietary Fats)
      0 (Isoenzymes)
      0 (Molecular Chaperones)
      0 (Peptides)
      0 (Prkcz protein, rat)
      0 (Srebf1 protein, rat)
      0 (Sterol Regulatory Element Binding Protein 1)
      106477-83-2 (pancreastatin)
      EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
      EC 2.7.11.1 (Gsk3b protein, rat)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
      EC 2.7.11.13 (Protein Kinase C)
      EC 2.7.11.13 (protein kinase C lambda)
    • Publication Date:
      Date Created: 20190902 Date Completed: 20200605 Latest Revision: 20200605
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.peptides.2019.170147
    • Accession Number:
      31473204