title: Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway.
abstract: Opuntia ficus-indicavar.saboten(OFS) has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, detailed mechanisms underlying hypoglycemic effects remain unclear. In this study, the mechanism underlying the hypoglycemic activity of OFS was evaluated using in vitro and in vivo systems. OFS treatment inhibited α-glucosidase activity and intestinal glucose absorption assessed by Na⁺-dependent glucose uptake using brush border membrane vesicles. AMP-activated protein kinase (AMPK) is widely recognized as an important regulator of glucose transport in skeletal muscle, and p38 mitogen-activated protein kinase (MAPK) has been proposed to be a component of AMPK-mediated signaling. In the present study, OFS dose-dependently increased glucose uptake in L6 muscle cells. The AMPK and p38 MAPK phosphorylations were stimulated by OFS, and inhibitors of AMPK (compoundC) and p38 MAPK (SB203580) abolished the effects of OFS. Furthermore, OFS increased glucose transporter 4 (GLUT4) translocation to the plasma membrane. OFS administration (1 g/kg and 2 g/kg body weight) indb/dbmice dose-dependently ameliorated hyperglycemia, hyperinsulinemia, and glucose tolerance. Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were also dose-dependently improved with OFS treatment. OFS administration improved pancreatic function through increased β-cell mass indb/dbmice. These findings suggest that OFS acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway.
authors.affiliation: College of Korean Medicine, Semyung University, Chungbuk 27136, Korea. heavenok@dreamwiz.com.
authors.forename: Kang-Hyun
authors.initials: KH
authors.lastname: Leem
authors.affiliation: College of Korean Medicine, Semyung University, Chungbuk 27136, Korea. ehdfkd@hanmail.net.
authors.forename: Myung-Gyou
authors.initials: MG
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Chung-Ang University, Gyeonggi 17546, Korea. ythahm@cau.ac.kr.
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Hahm
authors.affiliation: Department of Food & Biotechnology, Hanseo University, Seosan 31962, Korea. hkkim111@dreamwiz.com.
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007583:Jejunum / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008871:Microvilli / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism; D029747:Opuntia / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D000520:alpha-Glucosidases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D010936:Plant Extracts; C495694:Slc2a4 protein, rat; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D000520:alpha-Glucosidases; D005947:Glucose
keywords: AMPK; GLUT4; L6 myoblasts; Opuntia ficus-indica var. saboten; db/db mice; glucose uptake; p38 MAPK