Angptl4 links alpha-cell proliferation following glucagon receptor inhibition with adipose tissue triglyceride metabolism

作者：Ben Zvi Danny^*; Barrandon Ornella; Hadley Stephanie; Blum Barak; Peterson Quinn P; Melton Douglas A

来源：Proceedings of the National Academy of Sciences of the United States of America, 2015, 112(50): 15498-15503.

DOI：10.1073/pnas.1513872112

• diabetes
• metabolism
• angiopoietin
• glucagon
• LPL

Type 2 diabetes is characterized by a reduction in insulin function and an increase in glucagon activity that together result in hyperglycemia. Glucagon receptor antagonists have been developed as drugs for diabetes; however, they often increase glucagon plasma levels and induce the proliferation of glucagon-secreting alpha-cells. We find that the secreted protein Angiopoietin-like 4 (Angptl4) is up-regulated via Ppar gamma activation in white adipose tissue and plasma following an acute treatment with a glucagon receptor antagonist. Induction of adipose angptl4 and Angptl4 supplementation promote alpha-cell proliferation specifically. Finally, glucagon receptor antagonist improves glycemia in diet-induced obese angptl4 knockout mice without increasing glucagon levels or alpha-cell proliferation, underscoring the importance of this protein. Overall, we demonstrate that triglyceride metabolism in adipose tissue regulates alpha-cells in the endocrine pancreas.

• 出版日期2015-12-15