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Imaging Calcium Dynamics in Subpopulations of Mouse Pancreatic Islet Cells
Published on: November 26, 2019
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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
Summary
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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