The Two Faces of Protein Palmitoylation in Islet β-Cell Function: Potential Implications in the Pathophysiology of Islet Metabolic Dysregulation and Diabetes
Abiy M. Mohammed,
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.
Keywords: 2-Bromo-palmitate, cerulenin, palmitoylation, palmitoyl esterase, palmitoyl transferase, pancreatic β-cells, proinflammatory
cytokines, therapeutic targets, type 1 diabetes, and type 2 diabetes.
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