Protein prenylation in glucose‐induced insulin secretion from the pancreatic islet β cell: a perspective

•  Insulin secretion – a simplified view •  Endogenous GTP and its binding proteins are important for GSIS •  G‐proteins undergo post‐translational modifications •  Data accrued from studies involving generic inhibitors of protein prenylation •  Data accrued from studies involving site‐specific inhibitors of protein prenylation ‐  Lovastatin (LOVA) ‐  Limonene ‐  Perillic acid (PA) ‐  Manumycin A•  Data accrued from studies involving over‐expression of inactive mutants of PPTases ‐  3‐Allyl and‐vinyl farnesols and geranylgeraniols•  What are the functional consequences of prenylation in the islet β cell? •  How are PPTases regulated by glucose in the islet? •  Conclusions and future directionsAbstract Insulin secretion from the pancreatic β cell is regulated principally by the ambient concentration of glucose. However, the molecular and cellular mechanisms underlying the stimulus – secretion coupling of glucose‐stimulated insulin secretion (GSIS) remain only partially understood. Emerging evidence from multiple laboratories suggests key regulatory roles for GTP‐binding proteins in the cascade of events leading to GSIS. This class of signalling proteins undergoes a series of requisite post‐translational modifications ( e.g. prenylation) at their C‐terminal cysteines, which appear to be necessary for their targeting to respective membranous sites for optimal interaction with their respective effector proteins. This communication represents a perspective on potential regulatory roles for protein prenylation steps ( i.e. protein farnesylation and protein geranylgeranylation) in GSIS from the islet β cell.Possible consequences of protein prenylation and potential mechanisms underlying glucose‐induced regulation of prenylation, specifically in the context of GSIS, are also discussed.