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Nat Commun ; 15(1): 4410, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782979

RESUMO

Pancreatic ß 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.


Assuntos
Encéfalo , Proteínas de Drosophila , Drosophila melanogaster , Secreção de Insulina , Insulina , Animais , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Encéfalo/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Eixo Encéfalo-Intestino/fisiologia , Lipase/metabolismo , Lipase/genética , Gorduras na Dieta/metabolismo , Glucose/metabolismo , Corpo Adiposo/metabolismo , Lipase Lipoproteica/metabolismo , Lipase Lipoproteica/genética , Masculino
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