Angiopoietin-like peptide 4 regulates insulin secretion and islet morphology

作者：Kim Hyun Kyong; Kwon Obin; Park Kyeong Han; Lee Kyung Jin; Youn Byung Soo; Kim Seung Whan; Kim Min Seon^*

来源：Biochemical and Biophysical Research Communications, 2017, 485(1): 113-118.

DOI：10.1016/j.bbrc.2017.02.031

• Angiopoietin-like protein 4 (Angptl4)
• Pancreas
• Insulin secretion
• Protein kinase A

Insulin secretion from pancreatic islet beta-cells is primarily regulated by the blood glucose level, and also modulated by a number of biological factors produced inside the islets or released from remote organs. Previous studies have shown that angiopoietin-like protein 4 (Angptl4) controls glucose and lipid metabolism through its actions in the liver, adipose tissue, and skeletal muscles. In this present study, we investigated the possible role of Angptl4 in the regulation of insulin secretion from pancreatic islets. Angptl4 was found to be highly expressed in the alpha-cells but not beta-cells of rodent islets. Moreover, treatment of rodent islets with Angptl4 peptide potentiated glucose-stimulated insulin secretion through a protein kinase A-dependent mechanism. Consistently, Angptl4 knockout mice showed impaired glucose tolerance. In the cultured islets from Angptl4 knockout mice, glucose-stimulated insulin secretion was significantly lower than in islets from wild type mice. Angptl4 peptide replacement partially reversed this reduction. Moreover, Angptl4 knockout mice had dysmorphic islets with abnormally distributed alpha-cells. In contrast, the beta-cell mass and distribution were not significantly altered in these knockout mice. Our current data collectively suggest that Angptl4 may play a critical role in the regulation of insulin secretion and islet morphogenesis.

• 出版日期2017-3-25