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-indica var. 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 (compound C) 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) in db/db mice 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 in db/db mice. 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.

Transcriptome and Differential Expression Profiling Analysis of the Mechanism of Ca2+ Regulation in Peanut (Arachis hypogaea) Pod Development

“…The up-regulated expression of LOXs in GS is likely to provide sufficient nutrient preparation for pod development. Combined with the high expression of several energy- and substance-related transporter genes, which play critical roles in nutrient uptake and signal transduction (Leem et al, 2016 ), exogenous calcium probably promotes nutrient storage in the aerial gynophores, ascertaining the early development of pod.…”

An Overview of Herbal Products and Secondary Metabolites Used for Management of Type Two Diabetes

“…Polysaccharide ODP-Ia has been isolated from Opuntia dillenii Haw., and this was shown to have antihyperglycemic effects through the protection of the liver from peroxidation damage and through the maintenance of tissue function, thereby improving the sensitivity of target cells to insulin ( Zhao et al, 2011 ). Recent study conducted on murine model suggested that Opuntia ficus-indica treatment acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway ( Leem et al, 2016 ). Findings of a recent study conducted on Mexican patients with type 2 diabetes suggest that O. ficus-indica (L.) Mill.…”

Hypoglycemic effect of whole grain diet in C57BL/KsJ-db/db mice by activating PI3K/Akt and AMPK pathways

“…5A, B). AMPK induces GLUT4 recruitment to the plasma membrane by activating its downstream effector, p38 MAPK, which is an insulin-independent mechanism for GLUT4 translocation (Leem et al, 2016). Increased free fatty acids in the blood are another element that induces insulin resistance in target cells.…”

“…AMP-activated protein kinase (AMPK) is a major protein involved in regulation of energy homeostasis in cells (Hardie et al, 2012). Activation of AMPK not only recruits GLUT4 to the cell membrane through phosphorylation of p38 mitogen-activated protein kinase (MAPK) but also reduces synthesis of malonyl-CoA or a precursor of free fatty acids by inactivating acetyl-CoA carboxylase (ACC) (Day et al, 2017;Leem et al, 2016;Smith et al, 2016).…”