Glucose-induced [Ca2+]i oscillations in single human pancreatic islets

Area of Science:

• Endocrinology
• Cell Physiology
• Calcium Signaling

Background:

• Cytosolic free calcium concentrations ([Ca2+]i) are critical for regulated insulin secretion from pancreatic islets.
• Understanding the dynamics of [Ca2+]i in response to glucose is essential for elucidating glucose-stimulated insulin secretion (GSIS).

Purpose of the Study:

• To investigate the changes in cytosolic free calcium concentrations ([Ca2+]i) in human pancreatic islets in response to varying glucose concentrations.
• To characterize the pattern, synchronicity, and modulation of glucose-induced [Ca2+]i responses in human islets.

Main Methods:

• Human pancreatic islets were utilized for the study.
• Fura-2 fluorescence imaging was employed to measure cytosolic free calcium concentrations ([Ca2+]i).
• Stimulatory glucose concentrations (3 mM to 16.7 mM), tolbutamide, and diazoxide were used to elicit and modulate [Ca2+]i responses.

Main Results:

• Increasing glucose from 3 to 11 mM induced a triphasic [Ca2+]i response: initial decrease, transient increase, and periodic oscillations (1 +/- 0.3 min-1).
• Higher glucose (11 to 16.7 mM) reduced oscillation frequency (0.15 +/- 0.2 min-1) without altering amplitude.
• Glucose-induced [Ca2+]i responses were synchronous throughout the human islet.
• Tolbutamide stimulated a rise in [Ca2+]i, while diazoxide decreased [Ca2+]i in the presence of glucose.

Conclusions:

• Human islets respond to glucose with regular, islet-wide synchronous [Ca2+]i oscillations.
• The duration and frequency of these glucose-induced calcium oscillations are modulated by glucose concentration.
• These findings provide insights into the mechanisms of glucose sensing and insulin secretion in human pancreatic islets.