Cholinergic augmentation of insulin release requires ankyrin-B

Sci Signal. 2010 Mar 16;3(113):ra19. doi: 10.1126/scisignal.2000771.


Parasympathetic stimulation of pancreatic islets augments glucose-stimulated insulin secretion by inducing inositol trisphosphate receptor (IP(3)R)-mediated calcium ion (Ca2+) release. Ankyrin-B binds to the IP(3)R and is enriched in pancreatic beta cells. We found that ankyrin-B-deficient islets displayed impaired potentiation of insulin secretion by the muscarinic agonist carbachol, blunted carbachol-mediated intracellular Ca2+ release, and reduced the abundance of IP3R. Ankyrin-B-haploinsufficient mice exhibited hyperglycemia after oral ingestion but not after intraperitoneal injection of glucose, consistent with impaired parasympathetic potentiation of glucose-stimulated insulin secretion. The R1788W mutation of ankyrin-B impaired its function in pancreatic islets and is associated with type 2 diabetes in Caucasians and Hispanics. Thus, defective glycemic regulation through loss of ankyrin-B-dependent stabilization of IP3R is a potential risk factor for type 2 diabetes.

MeSH terms

  • Animals
  • Ankyrins / deficiency
  • Ankyrins / genetics
  • Ankyrins / metabolism*
  • Calcium / metabolism
  • Carbachol / metabolism
  • Diabetes Mellitus, Type 2 / metabolism*
  • Glucose / metabolism
  • Immunoblotting
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism*
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Microscopy, Fluorescence
  • Mutation, Missense
  • Parasympathetic Nervous System / metabolism*
  • Polymorphism, Single Nucleotide / genetics
  • RNA, Small Interfering / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors


  • Ank2 protein, mouse
  • Ankyrins
  • Inositol 1,4,5-Trisphosphate Receptors
  • Insulin
  • RNA, Small Interfering
  • Carbachol
  • Glucose
  • Calcium