We have explored whether gamma-aminobutyric acid (GABA) is released by regulated exocytosis of GABA-containing synaptic-like microvesicles (SLMVs) in insulin-releasing rat pancreatic beta-cells. To this end, beta-cells were engineered to express GABA(A)-receptor Cl(-)-channels at high density using adenoviral infection. Electron microscopy indicated that the average diameter of the SLMVs is 90 nm, that every beta-cell contains approximately 3,500 such vesicles, and that insulin-containing large dense core vesicles exclude GABA. Quantal release of GABA, seen as rapidly activating and deactivating Cl(-)-currents, was observed during membrane depolarizations from -70 mV to voltages beyond -40 mV or when Ca(2+) was dialysed into the cell interior. Depolarization-evoked GABA release was suppressed when Ca(2+) entry was inhibited using Cd(2+). Analysis of the kinetics of GABA release revealed that GABA-containing vesicles can be divided into a readily releasable pool and a reserve pool. Simultaneous measurements of GABA release and cell capacitance indicated that exocytosis of SLMVs contributes approximately 1% of the capacitance signal. Mathematical analysis of the release events suggests that every SLMV contains 0.36 amol of GABA. We conclude that there are two parallel pathways of exocytosis in pancreatic beta-cells and that release of GABA may accordingly be temporally and spatially separated from insulin secretion. This provides a basis for paracrine GABAergic signaling within the islet.
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http://dx.doi.org/10.1085/jgp.200308966 | DOI Listing |
Acta Physiol (Oxf)
February 2025
Faculty of Medicine, University of Maribor, Maribor, Slovenia.
Background: The crucial steps in beta cell stimulus-secretion coupling upon stimulation with glucose are oscillatory changes in metabolism, membrane potential, intracellular calcium concentration, and exocytosis. The changes in membrane potential consist of bursts of spikes, with silent phases between them being dominated by membrane repolarization and absence of spikes. Assessing intra- and intercellular coupling at the multicellular level is possible with ever-increasing detail, but our current ability to simultaneously resolve spikes from many beta cells remains limited to double-impalement electrophysiological recordings.
View Article and Find Full Text PDFDiabetes Obes Metab
January 2025
School of Exercise and Health, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, China.
Aims: To investigate the role of chemerin reduction in mediating exercise-induced Glucagon-like peptide-1 (GLP-1) secretion and the amelioration of pancreatic β-cell function in obesity.
Materials And Methods: Obesity models were established using wild-type and chemerin systemic knockout mice, followed by 8 weeks of moderate-intensity continuous aerobic exercise training. Serum chemerin levels, GLP-1 synthesis, glucose tolerance, pancreatic β-cell function, structure, and apoptosis were assessed.
J Biosci Bioeng
January 2025
Department of Chemical Systems Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan. Electronic address:
The bioartificial pancreas, composed of a semi-permeable hydrogel encapsulating insulin-secreting cells, has attracted attention as a treatment for type 1 diabetes. In this study, we developed phospholipid polymer-modified alginate hydrogel beads that encapsulated spheroids of the pancreatic beta cell line MIN6. The hydrogel beads were composed of methacrylated alginic acid, which enabled both ionic and covalent cross-linking, resulting in a hydrogel that was more stable than conventional alginate hydrogels.
View Article and Find Full Text PDFToxicology
January 2025
School of Public Health, Dali University, Dali, Yunnan, China; Institute of Preventive Medicine, Dali University, Dali, Yunnan, China. Electronic address:
N-methyladenosine (mA) modification and LncRNAs play crucial regulatory roles in various pathophysiological processes, yet roles of mA modification and the relationship between mA modification and LncRNAs in cadmium-induced oxidative damage of pancreatic β-cells have not been fully elucidated. In this study, mA agonist entacapone and inhibitor 3-deazadenosine were used to identify the effects of mA on cadmium-induced oxidative damage as well as LncRNA changes. Our results indicate that elevated levels of mA modification by entacapone can rescue the cell viability and attenuate the cell apoptosis, while the inhibition levels of mA modification can exacerbate the cell death.
View Article and Find Full Text PDFLife Sci
January 2025
School of Life Science and Technology, Shandong Second Medical University, Weifang 261021, China. Electronic address:
The forkhead box O1 (FOXO1), the first discovered member of the FoxO family, is a critical transcription factor predominantly found in insulin-secreting and insulin-sensitive tissues. In the pancreas of adults, FoxO1 expression is restricted to islet β cells. We determined that in human islet microarray datasets, FoxO1 expression is higher than other FoxO transcription factors.
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