{Reference Type}: Journal Article
{Title}: Global deletion of G protein-coupled receptor 55 impairs glucose homeostasis during obesity by reducing insulin secretion and β-cell turnover.
{Author}: Liu B;Ruz-Maldonado I;Persaud SJ;
{Journal}: Diabetes Obes Metab
{Volume}: 0
{Issue}: 0
{Year}: 2024 Aug 7
{Factor}: 6.408
{DOI}: 10.1111/dom.15816
{Abstract}: <B>OBJECTIVE: </B>To investigate the effect of G protein-coupled receptor 55 (GPR55) deletion on glucose homeostasis and islet function following diet-induced obesity.<BR><B>METHODS: </B>GPR55-/- and wild-type (WT) mice were fed ad libitum either standard chow (SC) or a high-fat diet (HFD) for 20 weeks. Glucose and insulin tolerance tests were performed at 9/10 and 19/20 weeks of dietary intervention. Insulin secretion in vivo and dynamic insulin secretion following perifusion of isolated islets were also determined, as were islet caspase-3/7 activities and β-cell 5-bromo-20-deoxyuridine (BrdU) incorporation.<BR><B>RESULTS: </B>GPR55-/- mice fed a HFD were more susceptible to diet-induced obesity and were more glucose intolerant and insulin resistant than WT mice maintained on a HFD. Islets isolated from HFD-fed GPR55-/- mice showed impaired glucose- and pcacahorbol 12-myristate 13-acetate-stimulated insulin secretion, and they also displayed increased cytokine-induced apoptosis. While there was a 5.6 ± 1.6-fold increase in β-cell BrdU incorporation in the pancreases of WT mice fed a HFD, this compensatory increase in β-cell proliferation in response to the HFD was attenuated in GPR55-/- mice.<BR><B>CONCLUSIONS: </B>Under conditions of diet-induced obesity, GPR55-/- mice show impaired glucose handling, which is associated with reduced insulin secretory capacity, increased islet cell apoptosis and insufficient compensatory increases in β-cell proliferation. These observations support that GPR55 plays an important role in positively regulating islet function.