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Imaging Calcium Dynamics in Subpopulations of Mouse Pancreatic Islet Cells
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Sulfonylurea Blockade of KATP Channels Unmasks a Distinct Type of Glucose-Induced Ca2+ Decrease in Pancreatic β-Cells

Bo Hellman1, Heléne Dansk, Eva Grapengiesser

  • 1From the Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.

Pancreas
|February 24, 2017
PubMed
Abstract

Insights

Sulfonylurea blockade of ATP-sensitive potassium (KATP) channels suppresses early calcium signals essential for glucose-stimulated insulin release in pancreatic beta-cells.

Area of Science:

  • Endocrinology
  • Cell Physiology
  • Molecular Biology

Background:

  • Insulin secretion is regulated by glucose levels, involving changes in intracellular calcium (Ca).
  • ATP-sensitive potassium (KATP) channels play a critical role in mediating glucose-induced insulin release.
  • Understanding the precise mechanisms of Ca signaling in beta-cells is crucial for diabetes research.

Purpose of the Study:

  • To investigate the impact of sulfonylurea drugs, which block KATP channels, on early calcium signals during glucose-stimulated insulin secretion.
  • To elucidate the role of KATP channels in the regulation of intracellular Ca dynamics in pancreatic beta-cells.

Main Methods:

  • Ratiometric microfluorometry using Fura-PE3 was employed to measure cytoplasmic Ca in isolated mouse islets.
  • Experiments involved blocking KATP channels with sulfonylureas (tolbutamide, gliclazide) and modulating other cellular pathways (Na/K pump, α2A adrenoceptors, SERCA pump).

Main Results:

  • Blockade of KATP channels by sulfonylureas suppressed the glucose-induced rise in cytoplasmic Ca.
  • Inhibition of the Na/K pump shortened the Ca decrease, while activation of α2A adrenoceptors prolonged it.
  • Inhibition of the sarco/endoplasmic reticulum Ca-ATPase (SERCA) pump counteracted the prolonged Ca decrease induced by α2A adrenoceptor activation.

Conclusions:

  • Glucose stimulation causes rapid suppression of cytoplasmic Ca in beta-cells with non-functional KATP channels.
  • α2A adrenoceptor activation significantly extends the duration of glucose-induced Ca reduction, an effect reversible by SERCA pump inhibition.

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