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ER stress and unfolded protein response (UPR) signaling modulate GLP-1 receptor signaling in the pancreatic islets.
Gao, Yurong; Ryu, Hanguk; Lee, Hyejin; Kim, Young-Joon; Lee, Ji-Hye; Lee, Jaemin.
Afiliación
  • Gao Y; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
  • Ryu H; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
  • Lee H; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
  • Kim YJ; Department of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
  • Lee JH; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
  • Lee J; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea; New Biology Research Center, DGIST, Daegu 42988, Republic of Korea; Well Aging Research Center, DGIST, Daegu 42988, Republic of Korea.
Mol Cells ; 47(1): 100004, 2024 Jan.
Article en En | MEDLINE | ID: mdl-38376482
ABSTRACT
Insulin is essential for maintaining normoglycemia and is predominantly secreted in response to glucose stimulation by ß-cells. Incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, also stimulate insulin secretion. However, as obesity and type 2 diabetes worsen, glucose-dependent insulinotropic polypeptide loses its insulinotropic efficacy, whereas GLP-1 receptor (GLP-1R) agonists continue to be effective owing to its signaling switch from Gs to Gq. Herein, we demonstrated that endoplasmic reticulum (ER) stress induced a transition from Gs to Gq in GLP-1R signaling in mouse islets. Intriguingly, chemical chaperones known to alleviate ER stress, such as 4-PBA and TUDCA, enforced GLP-1R's Gq utilization rather than reversing GLP-1R's signaling switch induced by ER stress or obese and diabetic conditions. In addition, the activation of X-box binding protein 1 (XBP1) or activating transcription factor 6 (ATF6), 2 key ER stress-associated signaling (unfolded protein response) factors, promoted Gs utilization in GLP-1R signaling, whereas Gq employment by ER stress was unaffected by XBP1 or ATF6 activation. Our study revealed that ER stress and its associated signaling events alter GLP-1R's signaling, which can be used in type 2 diabetes treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Islotes Pancreáticos / Respuesta de Proteína Desplegada / Estrés del Retículo Endoplásmico / Receptor del Péptido 1 Similar al Glucagón Límite: Animals Idioma: En Revista: Mol Cells Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Islotes Pancreáticos / Respuesta de Proteína Desplegada / Estrés del Retículo Endoplásmico / Receptor del Péptido 1 Similar al Glucagón Límite: Animals Idioma: En Revista: Mol Cells Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos