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.
Highlights
Type 2 diabetes mellitus (T2DM) has rapidly become the most prevalent chronic disease worldwide and remains one of the major health challenges of the 21st century
Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were dose-dependently improved with Opuntia ficus-indica var. saboten (OFS) treatment
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 AMP‐activated protein kinase (AMPK)/p38 mitogen-activated protein kinase (MAPK) signaling pathway
Summary
Type 2 diabetes mellitus (T2DM) has rapidly become the most prevalent chronic disease worldwide and remains one of the major health challenges of the 21st century. One of the therapeutic approaches for decreasing postprandial hyperglycemia is to retard the absorption of glucose by inhibition of carbohydrate-hydrolyzing enzymes such as α-amylase and α-glycosidase. They are not able to prevent glucose absorption when glucose itself has been ingested. Nutrients 2016, 8, 800 epithelia [1] It has been shown in diabetic animals and humans that the capacity of the small intestine to absorb glucose increases at the brush border membrane vesicles (BBMVs) due to the enhanced activity and abundance of SGLT1 [2,3]
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