Endocrine Abstracts

G-Protein-Coupled Receptors, GPR 120 and GPR 40, are potential avenues for treating type 2 diabetes. This study aimed to use natural GPR 120/GPR40 agonist flaxseed oil to investigate the mechanistic function of downstream signalling in islets and peripheral tissues. C57BL/6 mice, on a 12 week high-fat-fed (HFF) diet supplemented with streptozotocin (40mg/kg x 5) were treated with flaxseed oil for 21-days. After 21 days, islet and peripheral tissues assessed morphology, protein expression and proliferation (immunohistochemistry), tissue genes and intracellular signalling (qPCR). In HFF mice, β-cell proliferation increased (122%, P < 0.001), β-cell mass decreased (59%, P < 0.01), β-cell area increased (1%, P < 0.01) and α-cell mass decreased (89%, P < 0.01). HFF jejunal gene expression of GPR 120 (69%, P < 0.05), GPR 40 (116%, P < 0.01), CCK (58%, P < 0.001) and JNK 2 (141%, P < 0.01) increased with flaxseed oil administration. In flaxseed-treated HFF mice, ileum GPR 120 (150%, P < 0.05), GPR 40 (671%, P < 0.01), JNK 2 (133%, P < 0.05) and p 38 (75%, P < 0.05) gene expression augmented. Duodenum gene expression of GPR 120 (113%, P < 0.01), GPR 40 (233%, P < 0.01), ERK 2 (256%, P < 0.01), JNK 2 (89%, P < 0.01) and p 38 (400%, P < 0.001) upregulated. HFF colon gene expression was upregulated for GLP-1 (163%, P < 0.01), JNK 1 (145%, P < 0.01), ERK 1 (100%, P < 0.05), but downregulated for ERK 2 (75%, P < 0.001) and p 38 (67%, P < 0.01). In peripheral tissues, HFF adipose gene expression increased for GPR 120 (180%, P < 0.01), GPR 40 (431%, P < 0.01), ERK 1 (200%, P < 0.01), ERK 2 (74%, P < 0.01), but reduced for JNK 1 (82%, P < 0.01) and HFF liver p 38 gene expression (64%, P < 0.05). GPR 120 and GPR 40 are promising type 2 diabetes treatments, as omega-3 induced activation promotes β-cell proliferation, elicits anti-inflammatory effects, and modulates islet function.