PDF(Pubmed)
Abstract：
Pancreatic β cells secrete insulin in response to glucose elevation to maintain glucose homeostasis. A complex network of inter-organ communication operates to modulate insulin secretion and regulate glucose levels after a meal. Lipids obtained from diet or generated intracellularly are known to amplify glucose-stimulated insulin secretion, however, the underlying mechanisms are not completely understood. Here, we show that a Drosophila secretory lipase, Vaha (CG8093), is synthesized in the midgut and moves to the brain where it concentrates in the insulin-producing cells in a process requiring Lipid Transfer Particle, a lipoprotein originating in the fat body. In response to dietary fat, Vaha stimulates insulin-like peptide release (ILP), and Vaha deficiency results in reduced circulatory ILP and diabetic features including hyperglycemia and hyperlipidemia. Our findings suggest Vaha functions as a diacylglycerol lipase physiologically, by being a molecular link between dietary fat and lipid amplified insulin secretion in a gut-brain axis.
摘要：
胰腺β细胞响应于葡萄糖升高而分泌胰岛素以维持葡萄糖稳态。复杂的器官间通信网络可以调节胰岛素分泌并调节餐后的葡萄糖水平。已知从饮食中获得或在细胞内产生的脂质会增强葡萄糖刺激的胰岛素分泌，然而,潜在的机制还没有完全理解。这里,我们发现果蝇分泌脂肪酶，瓦哈(CG8093),在中肠中合成并移动到大脑，在需要脂质转移颗粒的过程中，它集中在胰岛素产生细胞中，起源于脂肪体内的脂蛋白。为了应对膳食脂肪，Vaha刺激胰岛素样肽释放（ILP），和Vaha缺乏导致循环ILP减少和糖尿病特征，包括高血糖和高脂血症。我们的发现表明，Vaha在生理上充当二酰基甘油脂肪酶，通过膳食脂肪和脂质之间的分子联系，增加了肠-脑轴中的胰岛素分泌。
