دورية أكاديمية

Mechano-sensor Piezo1 inhibits glucagon production in pancreatic α-cells.

التفاصيل البيبلوغرافية
العنوان: Mechano-sensor Piezo1 inhibits glucagon production in pancreatic α-cells.
المؤلفون: Guo W; Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong 510632, China., Gao L; Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong 510632, China., Mo H; Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong 510632, China., Deng H; Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong 510632, China., Zhao Y; Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong 510632, China., Xu G; Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong 510632, China; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, Guangdong, China. Electronic address: xugeyangliang@163.com.
المصدر: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Jun; Vol. 1870 (5), pp. 167185. Date of Electronic Publication: 2024 Apr 21.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-260X (Electronic) Linking ISSN: 09254439 NLM ISO Abbreviation: Biochim Biophys Acta Mol Basis Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier
مواضيع طبية MeSH: Glucagon-Secreting Cells*/metabolism , Glucagon*/metabolism , Ion Channels*/metabolism , Ion Channels*/genetics , Mice, Knockout* , Diet, High-Fat*/adverse effects, Animals ; Mice ; Male ; Signal Transduction ; Insulin/metabolism ; Cell Line ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mechanistic Target of Rapamycin Complex 1/genetics ; Mechanotransduction, Cellular ; Mice, Inbred C57BL ; Proglucagon/metabolism ; Proglucagon/genetics ; Pyrazines ; Thiadiazoles
مستخلص: Objective: Glucagon is a critical hormone regulating glucose metabolism. It stimulates the liver to release glucose under low blood sugar conditions, thereby maintaining blood glucose stability. Excessive glucagon secretion and hyperglycemia is observed in individuals with diabetes. Precise modulation of glucagon is significant to maintain glucose homeostasis. Piezo1 is a mechanosensitive ion channel capable of converting extracellular mechanical forces into intracellular signals, thus regulating hormonal synthesis and secretion. This study aims to investigate the role of Piezo1 in regulating glucagon production in α cells.
Methods: The effects of Piezo1 on glucagon production were examined in normal- or high-fat diet fed α cell-specific Piezo1 knockout mice (Gcg-Piezo1 -/- ), and the murine pancreatic α cell line αTC1-6. Expression of Proglucagon was investigated by real-time PCR and western blotting. Plasma glucagon and insulin were detected by enzyme immunoassay.
Results: Under both normal- and high-fat diet conditions, Gcg-Piezo1 -/- mice exhibited increased pancreatic α cell proportion, hyperglucagonemia, impaired glucose tolerance, and activated pancreatic mTORC1 signaling. Activation of Piezo1 by its agonist Yoda1 or overexpression of Piezo1 led to decreased glucagon synthesis and suppressed mTOR signaling pathway in αTC1-6 cells. Additionally, the levels of glucagon in the medium were also reduced. Conversely, knockdown of Piezo1 produced opposite effects.
Conclusion: Our study uncovers the regulatory role of the Piezo1 ion channel in α cells. Piezo1 influences glucagon production by affecting mTOR signaling pathway.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Glucagon; Piezo1; mTORC1; α cells
المشرفين على المادة: 0 (Piezo1 protein, mouse)
0 (yoda-1)
تواريخ الأحداث: Date Created: 20240423 Date Completed: 20240521 Latest Revision: 20240910
رمز التحديث: 20240910
DOI: 10.1016/j.bbadis.2024.167185
PMID: 38653360
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-260X
DOI:10.1016/j.bbadis.2024.167185