Chronic activation of GPR40 does not negatively impact upon BRIN-BD11 pancreatic β-cell physiology and function

• DOI: 10.1007/s43440-020-00101-6
• Publication Date: 2020-04-09T10:03:39Z
• Authors: Eloisa Aparecida ...; Noémie Karabacz; Gabriela Nunes Ma...; Maíra Melo Rezend...; Lisa Nalbach; Emmanuel Ampofo; Bruce Morgan; Angelo Rafael Car...; Leticia Prates Roma
• Keywords: Calcium in biology

Abstract 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 secretion. On the contrary, long-term saturated FFAs results in decreased secretion, well triggering oxidative stress endoplasmic reticulum (ER) stress, culminating cell death. The of can be mediated either via intracellular oxidation consequent cellular metabolism or activation membrane receptor GPR40. Both pathways likely activated upon both short- FFAs. However, precise role GPR40 physiology, especially chronic remains unclear. Methods We used agonist (GW9508) antagonist (GW1100) investigate impact chronically modulating activity BRIN-BD11 β-cells physiology function. Results observed that did not lead increased apoptosis, proliferation glucose-induced calcium entry were unchanged compared control conditions. also no increase H 2 O superoxide levels ER markers p-eIF2α, CHOP BIP. As expected, palmitate led levels, viability proliferation, entry. These changes counteracted by co-treatment palmitate-exposed cells with GW1100. Conclusions Chronic using GW9508 does negatively GW1100 protect against deleterious exposure. conclude is probably involved mediating toxicity associated