Thapsigargin inhibits the glucose-induced decrease of intracellular Ca2+ in mouse islets of Langerhans

Am J Physiol. 1994 Jun;266(6 Pt 1):E852-62. doi: 10.1152/ajpendo.1994.266.6.E852.


Stimulation of pancreatic islets of Langerhans with glucose results in changes in intracellular Ca2+ concentration ([Ca2+]i). With the use of mouse islets loaded with fura 2, the earliest glucose-induced alteration of [Ca2+]i was a pronounced decline in [Ca2+]i. This effect (phase 0) was evident 1 min after increasing extracellular glucose from 2 to 12 mM and was sustained for 3-5 min. Phase 0 was also observed when glucose was increased from 5 to 12 mM, indicating that it was not an experimental artifact resulting from substrate depletion. The [Ca2+]i-lowering effect of glucose was mimicked by D-glyceraldehyde but not by 2-deoxyglucose, pyruvate, glyburide, or 30 mM extracellular KCl. Mannoheptulose inhibited phase 0, whereas diazoxide, sodium azide, calmidazolium, or increasing extracellular [Ca2+] to 10 mM were all without effect. After the elevation of islet [Ca2+]i with 5 microM glyburide, 12 mM glucose caused a considerable transient decrease in [Ca2+]i. Under similar conditions, 5 mM caffeine attenuated phase 0, whereas 1 microM thapsigargin, a specific inhibitor of the sarcoplasmic and endoplasmic reticulum family of Ca(2+)-adenosinetriphosphatases (SERCA), almost completely inhibited any glucose-induced reduction of [Ca2+]i. These observations suggest that glucose causes an elevation of beta-cell SERCA activity triggered by factors generated during the cytosolic stages of glycolysis.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Calcium-Transporting ATPases / metabolism
  • Calmodulin / pharmacology
  • Cell Membrane / metabolism
  • Dose-Response Relationship, Drug
  • Endoplasmic Reticulum / metabolism
  • Glucose / antagonists & inhibitors
  • Glucose / pharmacology*
  • In Vitro Techniques
  • Intracellular Membranes / metabolism*
  • Islets of Langerhans / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Sarcoplasmic Reticulum / metabolism
  • Terpenes / pharmacology*
  • Thapsigargin


  • Calmodulin
  • Terpenes
  • Thapsigargin
  • Calcium-Transporting ATPases
  • Glucose
  • Calcium