C3aR1 on β cells Enhances β cell Function and Survival to Maintain Glucose Homeostasis DOI Creative Commons
Renan Pereira de Lima, Ang Li, Ankit Gilani

et al.

Molecular Metabolism, Journal Year: 2025, Volume and Issue: 96, P. 102134 - 102134

Published: April 6, 2025

Pancreatic β cell dysfunction is critical to the development of type 2 diabetes (T2D). Our previous studies suggested that C3aR1 on cells promotes insulin secretion and survival. However, as expressed many other types including within islets, whole-body knockout models confound analyses direct impacts cells. To clarify role in under T2D conditions, we generated cell-specific mice. We assessed glucose homeostasis, focusing function mass metabolic stress interrogate effects a mouse model T2D. performed proteomic islets from control determine potential translational relevance, C3AR1 was alongside glucose-stimulated human islets. show complement receptor plays an essential maintaining especially duress obesity Male mice with specific deletion C3ar1 (β-C3aR1 KO) exhibit worse tolerance lower levels when fed regular or high fat diet. Under diet, β-C3aR1 KO also have diminished mass. Islets demonstrate impaired secretion. lacking display increased susceptibility lipotoxicity-mediated death. Markers identity are decreased while markers elevated. Disruption ablates secretory response C3a, establishing signaling axis between C3a cell-derived C3aR1. Islet highlight MAPK pathway mitochondrial loss Finally, positively correlated These findings indicate expression necessary maintain optimal preserve

Language: Английский

C3aR1 on β cells Enhances β cell Function and Survival to Maintain Glucose Homeostasis DOI Creative Commons
Renan Pereira de Lima, Ang Li, Ankit Gilani

et al.

Molecular Metabolism, Journal Year: 2025, Volume and Issue: 96, P. 102134 - 102134

Published: April 6, 2025

Pancreatic β cell dysfunction is critical to the development of type 2 diabetes (T2D). Our previous studies suggested that C3aR1 on cells promotes insulin secretion and survival. However, as expressed many other types including within islets, whole-body knockout models confound analyses direct impacts cells. To clarify role in under T2D conditions, we generated cell-specific mice. We assessed glucose homeostasis, focusing function mass metabolic stress interrogate effects a mouse model T2D. performed proteomic islets from control determine potential translational relevance, C3AR1 was alongside glucose-stimulated human islets. show complement receptor plays an essential maintaining especially duress obesity Male mice with specific deletion C3ar1 (β-C3aR1 KO) exhibit worse tolerance lower levels when fed regular or high fat diet. Under diet, β-C3aR1 KO also have diminished mass. Islets demonstrate impaired secretion. lacking display increased susceptibility lipotoxicity-mediated death. Markers identity are decreased while markers elevated. Disruption ablates secretory response C3a, establishing signaling axis between C3a cell-derived C3aR1. Islet highlight MAPK pathway mitochondrial loss Finally, positively correlated These findings indicate expression necessary maintain optimal preserve

Language: Английский

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