A fundamental role
of pancreatic β-cells to maintain proper
blood glucose level is controlled by the Ras superfamily of small
GTPases that undergo post-translational modifications, including prenylation.
This covalent attachment with either a farnesyl or a geranylgeranyl
group controls their localization, activity, and protein–protein
interactions. Small GTPases are critical in maintaining glucose homeostasis
acting in the pancreas and metabolically active tissues such as skeletal
muscles, liver, or adipocytes. Hyperglycemia-induced upregulation
of small GTPases suggests that inhibition of these pathways deserves
to be considered as a potential therapeutic approach in treating T2D.
This Perspective presents how inhibition of various points in the
mevalonate pathway might affect protein prenylation and functioning
of diabetes-affected tissues and contribute to chronic inflammation
involved in diabetes mellitus (T2D) development. We also demonstrate
the currently available molecular tools to decipher the mechanisms
linking the mevalonate pathway’s enzymes and GTPases with diabetes.