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

Danny Ben-Zvi, Ornella Barrandon, Stephanie Hadley, Barak Blum, Quinn Peterson, Douglas A. Melton

Research output: Contribution to journalArticle

20 Scopus citations


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 α-cells. We find that the secreted protein Angiopoietin-like 4 (Angptl4) is up-regulated via Pparγ activation in white adipose tissue and plasma following an acute treatment with a glucagon receptor antagonist. Induction of adipose angptl4 and Angptl4 supplementation promote α-cell proliferation specifically. Finally, glucagon receptor antagonist improves glycemia in diet-induced obese angptl4 knockout mice without increasing glucagon levels or α-cell proliferation, underscoring the importance of this protein. Overall, we demonstrate that triglyceride metabolism in adipose tissue regulates α-cells in the endocrine pancreas.

Original languageEnglish (US)
Pages (from-to)15498-15503
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number50
StatePublished - Dec 15 2015
Externally publishedYes



  • Angiopoietin
  • Diabetes
  • Glucagon
  • LPL
  • Metabolism

ASJC Scopus subject areas

  • General

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