Glucose-insensitivity induced by Ca(2+) toxicity in islet beta-cells and its prevention by PACAP

Peptides. 2002 Jan;23(1):135-42. doi: 10.1016/s0196-9781(01)00589-7.


The present study examined whether a sustained increase in cytosolic Ca(2+) concentration ([Ca(2+)](i)) causes glucose-insensitivity in beta-cells and whether it could be modulated by pituitary adenylate cyclase-activating polypeptide (PACAP), a pancreatic insulinotropin. Rat single beta-cells were cultured for 2 days with sustained increases in [Ca(2+)](i), followed by determination of the [Ca(2+)](i) response to glucose (8.3 mM) as monitored with fura-2. High K(+) (25 mM) produced sustained increases in [Ca(2+)](i) in beta-cells, which were inhibited by nifedipine, a Ca(2+) channel blocker. After culture with high K(+), the incidence and amplitude of [Ca(2+)](i) responses to glucose were markedly reduced. This glucose-insensitivity was prevented by the presence of nifedipine or PACAP-38 (10(-13) M and 10-9) M) in high K(+) culture. PACAP-38 attenuated high K(+)-induced [Ca(2+)](i) increases. In conclusion, sustained increases in [Ca(2+)](i) induce glucose-insensitivity (Ca(2+) toxicity in beta-cells) and it is prevented by PACAP possibly in part due to its Ca(2+)-reducing capacity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cells, Cultured
  • Coloring Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Fluorescent Dyes / pharmacology
  • Fura-2 / pharmacology
  • Glucose / metabolism
  • Glucose / pharmacology*
  • Islets of Langerhans / metabolism*
  • Neuropeptides / pharmacology*
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Potassium / metabolism
  • Rats
  • Time Factors
  • Vasodilator Agents / pharmacology


  • Adcyap1 protein, rat
  • Coloring Agents
  • Fluorescent Dyes
  • Neuropeptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Vasodilator Agents
  • Glucose
  • Potassium
  • Calcium
  • Fura-2