The two faces of protein palmitoylation in islet β-cell function: potential implications in the pathophysiology of islet metabolic dysregulation and diabetes.

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  • Author(s): Mohammed AM;Mohammed AM; Chen F; Kowluru A
  • Source:
    Recent patents on endocrine, metabolic & immune drug discovery [Recent Pat Endocr Metab Immune Drug Discov] 2013 Sep; Vol. 7 (3), pp. 203-12.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Bentham Science Publishers Country of Publication: United Arab Emirates NLM ID: 101299743 Publication Model: Print Cited Medium: Internet ISSN: 2212-3334 (Electronic) Linking ISSN: 18722148 NLM ISO Abbreviation: Recent Pat Endocr Metab Immune Drug Discov Subsets: MEDLINE
    • Publication Information:
      Original Publication: Saif Zone, Sharjah, U.A.E. : Bentham Science Publishers, 2007-2017.
    • Subject Terms:
      Diabetes Mellitus/*metabolism ; Diabetes Mellitus/*physiopathology ; Insulin-Secreting Cells/*metabolism ; Insulin-Secreting Cells/*physiology ; Lipoylation/*physiology ; Pancreas/*metabolism ; Pancreas/*physiopathology ; Proteins/*physiology; Animals ; GTP-Binding Proteins/metabolism ; Glucose/pharmacology ; Humans ; Insulin/metabolism ; Lipoylation/drug effects ; Patents as Topic ; Proteins/metabolism
    • Abstract:
      Several cellular proteins undergo post-translational lipidation, including prenylation, palmitoylation and myristoylation, which are felt to promote intracellular targeting, membrane association and interaction with effector partner proteins. Recent findings implicate definitive roles of isoprenylation in islet β-cell function including glucose-stimulated insulin secretion [GSIS]. Published evidence also suggests novel regulatory roles for protein palmitoylation not only in GSIS but also in the metabolic dysfunction induced by proinflammatory cytokines and lipotoxic conditions. Herein, we overviewed the existing evidence on the regulatory roles of protein palmitoylation in the metabolic [dys]regulation of the islet β-cell and highlighted the developments in this area, specifically on potential identity of palmitoylated proteins, and on the utility of two structurally distinct inhibitors of palmitoylation [e.g., cerulenin and 2-bromopalmitate] in halting the metabolic dysfunction of the islet β-cell known to occur following exposure to proinflammatory cytokines and lipotoxic conditions. Potential avenues for future research, including the immediate need for discovery of novel small molecule compounds as inhibitors of palmitoyl transferases to attenuate deleterious consequences of proinflammatory cytokines and glucolipotoxicity are discussed. Furthermore, some relevant patents are also highlighted in this review.
    • Grant Information:
      R01 DK74921 United States DK NIDDK NIH HHS; R01 ES017217 United States ES NIEHS NIH HHS; R01 ES020137 United States ES NIEHS NIH HHS
    • Accession Number:
      0 (Insulin)
      0 (Proteins)
      EC 3.6.1.- (GTP-Binding Proteins)
      IY9XDZ35W2 (Glucose)
    • Publication Date:
      Date Created: 20130709 Date Completed: 20140326 Latest Revision: 20191112
    • Publication Date:
      20221213
    • Accession Number:
      10.2174/18722148113079990008
    • Accession Number:
      23829395