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Imaging Calcium Dynamics in Subpopulations of Mouse Pancreatic Islet Cells
Published on: November 26, 2019
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Similarities in Calcium Oscillations Between Neonatal Mouse Islets and Mature Islets Exposed to Chronic Hyperglycemia
Cathleen V D'Angelo1, Hannah L West1,2, Nicholas B Whitticar1,3
1Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA.
Endocrinology
|May 13, 2022
Summary
Neonatal islets exhibit immature calcium signaling patterns, similar to dedifferentiated diabetic islets. This suggests a "reverse maturation" in diabetes and offers insights into improving beta cell function.
Area of Science:
- Endocrinology
- Cell Biology
- Physiology
Background:
- Islet function relies on pulsatile intracellular calcium ([Ca2+]i) signaling, which matures as islets develop.
- Understanding neonatal islet calcium dynamics is crucial for insights into islet development and disease.
Purpose of the Study:
- To characterize intracellular calcium ([Ca2+]i) oscillations in neonatal mouse islets compared to adult islets.
- To investigate the role of ATP-sensitive potassium (KATP) channels in neonatal islet calcium signaling.
- To explore the relationship between neonatal islet calcium patterns and dedifferentiated diabetic islets.
Main Methods:
- Fluorescence imaging was used to measure [Ca2+]i oscillations in islets from neonatal (postnatal days 0, 4, 12) and adult mice.
- Islets were exposed to varying glucose concentrations (3 mM, 11 mM).
- Responses to KATP channel agents (diazoxide, tolbutamide) were assessed to estimate channel activity.
Main Results:
- Neonatal islets (PN days 0, 4) showed robust [Ca2+]i oscillations in low glucose, unlike adult islets.
- While oscillations were present in neonatal islets at stimulatory glucose, patterns differed from adults.
- By PN day 12, [Ca2+]i oscillations approached adult characteristics, suggesting maturation.
- Immature patterns were partly attributed to differences in KATP channel activity.
- Neonatal patterns mimicked mature islets under prolonged hyperglycemia, showing elevated [Ca2+]i and oscillations in low glucose.
Conclusions:
- Neonatal islets display distinct, immature calcium signaling patterns compared to adult islets.
- These immature patterns share similarities with dedifferentiated diabetic islets, suggesting a
- reverse maturation
- phenomenon in diabetes.
- Pulsatility is an emergent feature of neonatal islets, and studying these patterns may inform strategies to reverse beta cell dedifferentiation and improve stem cell-derived beta cells.
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