title: Octaphlorethol A, a marine algae product, exhibits antidiabetic effects in type 2 diabetic mice by activating AMP-activated protein kinase and upregulating the expression of glucose transporter 4.
abstract: Octaphlorethol A (OPA), a type of phlorotannin isolated from Ishige foliacea has been shown to have antidiabetic activities. However, the mechanism of action of OPA in type 2 diabetes has not been investigated extensively. Here, we investigated the antidiabetic effects and mechanism of OPA in C57BL/KsJ-db/db mice, a model of type 2 diabetes. Levels of postprandial blood glucose were significantly lower in OPAtreated db/db mice than in control db/db mice. In addition, the OPA supplements significantly improved fasting blood glucose level and impaired glucose tolerance compared to control db/db mice. OPA also significantly decreased the level of serum insulin, augmented the activation of AMP-activated protein kinase (AMPK), and increased the expression of glucose transporter 4 (GLUT4) protein in skeletal muscle. In addition, it significantly suppressed the increases in hepatic mRNA expression level of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), gluconeogenesis-related enzymes. Therefore, the mechanisms of OPA may involve suppression of gluconeogenesis by inhibiting PEPCK and G6Pase activity in the liver and affecting GLUT4-mediated glucose uptake in skeletal muscle through activation of AMPK. These findings provide a new insight into the antidiabetic clinical applications of OPA and demonstrate the potential of OPA as a new drug candidate for type 2 diabetes.
authors.affiliation: Division of Food Bioscience and Korea Nokyong Research Center, Konkuk University, Chungju, 27478, Republic of Korea.
authors.forename: Seung-Hong
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Marine-Integrated Bionics Research Center, Pukyong National University, Busan, 48513, Republic of Korea.
authors.forename: Seok-Chun
authors.initials: SC
authors.lastname: Ko
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, 21565, Republic of Korea. Electronic address: drhormone@naver.com.
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Marine Life Science, Jeju National University, Jeju, 63243, Republic of Korea. Electronic address: youjin2014@gmail.com.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Jeon
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D051275:Glucose Transporter Type 4 / Q000187:drug effects*; D008297:Male; D008386:Marine Biology; D051379:Mice; D008810:Mice, Inbred C57BL; D000459:Phaeophyceae / Q000737:chemistry*; D010636:Phenols / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D051275:Glucose Transporter Type 4; D010636:Phenols; C572462:octaphlorethol A; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; Glucose transporter 4; Glucose-6-phosphatase; Octaphlorethol A; Phosphoenolpyruvate carboxykinase; Type 2 diabetes