Primary Cilia in Pancreatic β- and α-Cells: Time to Revisit the Role of Insulin-Degrading Enzyme

Abstract

The primary cilium is a narrow organelle located at the surface of the cell in contact with the extracellular environment. Once underappreciated, now is thought to efficiently sense external environmental cues and mediate cell-to-cell communication, because many receptors, ion channels, and signaling molecules are highly or differentially expressed in primary cilium. Rare genetic disorders that affect cilia integrity and function, such as Bardet-Biedl syndrome and Alström syndrome, have awoken interest in studying the biology of cilium. In this review, we discuss recent evidence suggesting emerging roles of primary cilium and cilia-mediated signaling pathways in the regulation of pancreatic β- and α-cell functions, and its implications in regulating glucose homeostasis.

Single cell multiome profiling of pancreatic islets reveals physiological changes in cell type-specific regulation associated with diabetes risk

“…At a T2D signal on chromosome 11, risk variants increase the activity of a beta cell cRE linked to DEUP1 as well as DEUP1 expression in islets. DEUP1 is a component of cell division machinery 80 and, given in vitro evidence that DEUP1 can self-assemble 81 , increased DEUP1 activity and assembly may alter signal reception or microtubule dynamics 82 . Other genes linked to beta cell cREs affected by T2D risk variants include UBE2E2, which alters insulin secretion in mouse beta cells 83 , and CD101, which has no established role in beta cells.…”

Hepatic insulin-degrading enzyme regulation and its role on glucagon signaling

“…This pathological state alters the functional capacity of the pancreas and liver, contributing to the pathogenicity of T2DM [7,9,10]. In this line of evidence our group has made a substantial contribution to explain the role of IDE in α-cells on hyperglucagonemia [15,16], however this topic is out of the scope of this thesis.…”

“…Another putative explanation for GCGR lost may be cytoskeleton disarrangement. Recently, we reported that genetic depletion of Ide in α-cells (αTC1.9 cell line transfected with an Ide-targeting siRNA) resulted in cytoskeleton disarrangement and a significant reduction in the number of primary cilia [15,16].…”