Chronic activation of GPR40 does not negatively impact upon BRIN-BD11 pancreatic β-cell physiology and function
Autor: | Emmanuel Ampofo, Eloisa Aparecida Vilas-Boas, Angelo Rafael Carpinelli, Noémie Karabacz, Maíra Melo Rezende Valle, Bruce A. Morgan, Gabriela Nunes Marsiglio-Librais, Leticia Prates Roma, Lisa Nalbach |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cell physiology medicine.medical_specialty endocrine system Cell Survival Palmitates β-cells 030209 endocrinology & metabolism GPR40 activation Apoptosis APOPTOSE Palmitate medicine.disease_cause Benzoates Article Cell Line Receptors G-Protein-Coupled 03 medical and health sciences Methylamines 0302 clinical medicine Free fatty acid receptor 1 Internal medicine Insulin-Secreting Cells medicine Animals Viability assay Cell Proliferation Pharmacology Chemistry Endoplasmic reticulum General Medicine Hydrogen Peroxide Endoplasmic Reticulum Stress Rats 030104 developmental biology Endocrinology Pyrimidines Lipotoxicity Unfolded protein response Calcium Propionates Intracellular Oxidative stress |
Zdroj: | Pharmacological Reports Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
ISSN: | 2299-5684 1734-1140 |
Popis: | Background Free fatty acids (FFAs) are known for their dual effects on insulin secretion and pancreatic β-cell survival. Short-term exposure to FFAs, such as palmitate, increases insulin secretion. On the contrary, long-term exposure to saturated FFAs results in decreased insulin secretion, as well as triggering oxidative stress and endoplasmic reticulum (ER) stress, culminating in cell death. The effects of FFAs can be mediated either via their intracellular oxidation and consequent effects on cellular metabolism or via activation of the membrane receptor GPR40. Both pathways are likely to be activated upon both short- and long-term exposure to FFAs. However, the precise role of GPR40 in β-cell physiology, especially upon chronic exposure to FFAs, remains unclear. Methods We used the GPR40 agonist (GW9508) and antagonist (GW1100) to investigate the impact of chronically modulating GPR40 activity on BRIN-BD11 pancreatic β-cells physiology and function. Results We observed that chronic activation of GPR40 did not lead to increased apoptosis, and both proliferation and glucose-induced calcium entry were unchanged compared to control conditions. We also observed no increase in H2O2 or superoxide levels and no increase in the ER stress markers p-eIF2α, CHOP and BIP. As expected, palmitate led to increased H2O2 levels, decreased cell viability and proliferation, as well as decreased metabolism and calcium entry. These changes were not counteracted by the co-treatment of palmitate-exposed cells with the GPR40 antagonist GW1100. Conclusions Chronic activation of GPR40 using GW9508 does not negatively impact upon BRIN-BD11 pancreatic β-cells physiology and function. The GPR40 antagonist GW1100 does not protect against the deleterious effects of chronic palmitate exposure. We conclude that GPR40 is probably not involved in mediating the toxicity associated with chronic palmitate exposure. |
Databáze: | OpenAIRE |
Externí odkaz: |