Dexmedetomidine suppresses glucose-stimulated insulin secretion in pancreatic β-cells.

Autor: Kusunoki M; Department of Anesthesiology, Kansai Medical University, Hirakata, Osaka, Japan., Hirota K; Department of Pain Clinic Medicine, Minamiuonuma City Hospital, Minamiuonuma, Niigata, Japan., Shoji T; Department of Anesthesiology, Mitoyo General Hospital, Kan-onji, Kagawa, Japan., Uba T; Department of Anesthesiology, Kansai Medical University, Hirakata, Osaka, Japan., Matsuo Y; Department of Human Stress Response Science, Institute of Biomedical Science, Kansai Medical University, Hirakata, Osaka, Japan., Hayashi M; Department of Cell Physiology, Institute of Biomedical Science, Kansai Medical University, Hirakata, Osaka, Japan.
Jazyk: angličtina
Zdroj: FEBS open bio [FEBS Open Bio] 2024 Dec 20. Date of Electronic Publication: 2024 Dec 20.
DOI: 10.1002/2211-5463.13960
Abstrakt: Proper glycemic control is crucial for patient management in critical care, including perioperative care, and can influence patient prognosis. Blood glucose concentration determines insulin secretion and sensitivity and affects the intricate balance between the glucose metabolism. Human and other animal studies have demonstrated that perioperative drugs, including volatile anesthetics and intravenous anesthetics, affect glucose-stimulated insulin secretion (GSIS). Dexmedetomidine (DEX) decreases insulin release and affects glucose metabolism; however, the specific mechanism underlying this phenomenon remains largely unknown. Thus, we investigated the effect and mechanism of DEX on insulin secretion using mouse and rat pancreatic β-cell-derived MIN6 and INS-1 cell lines and primary pancreatic β-cells/islets extracted from mice. The amount of insulin secreted into the culture medium was determined using an enzyme-linked immunosorbent assay. Cell viability, cytotoxicity, and electrophysiological effects were investigated. Clinically relevant doses of DEX suppressed GSIS in MIN6 cells, INS-1 cells, and pancreatic β-cells/islets. Furthermore, DEX suppressed insulin secretion facilitated by insulinotropic factors. There was no significant difference in oxygen consumption rate, intracellular ATP levels, or caspase-3/7 activity. Electrophysiological evaluation using the patch-clamp method showed that DEX did not affect ATP-sensitive potassium (K ATP ) channels, voltage-dependent potassium channels, or voltage-gated calcium channels. We demonstrated that clinically relevant doses of DEX significantly suppressed GSIS. These findings suggest that DEX inhibits a signaling pathway via α2-adrenoceptor or insulin vesicle exocytosis, resulting in GSIS suppression. Our results support the hypothesis that DEX suppresses insulin secretion and reveal some underlying mechanisms.
(© 2024 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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