Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob mice.
Nobiletin is a polymethoxylated flavone found in certain citrus fruits that exhibits various pharmacological effects including anti-inflammatory, antitumor and neuroprotective properties. The present study investigated the effects of nobiletin on insulin sensitivity in obese diabetic ob/ob mice, and the possible mechanisms involved. The ob/ob mice were treated with nobiletin (200mg/kg) for 5 weeks. Nobiletin significantly improved the plasma glucose levels, homeostasis model assessment index, glucose tolerance in an oral glucose tolerance test and plasma adiponectin levels. In white adipose tissue (WAT), nobiletin significantly decreased the mRNA expression levels of inflammatory adipokines such as interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 and increased the mRNA expression levels of adiponectin, peroxisome proliferator-activated receptor (PPAR)-gamma and its target genes. At the same time, nobiletin increased the glucose transporter (Glut) 4 expression levels in the whole plasma membrane, and Glut1 and phospho-Akt expression in the whole cell lysates in WAT and muscle. Nobiletin also increased Glut4 protein expression level in the whole cell lysates of the muscle. Taken together, the present results suggest that nobiletin improved the hyperglycemia and insulin resistance in obese diabetic ob/ob mice by regulating expression of Glut1 and Glut4 in WAT and muscle, and expression of adipokines in WAT.
Research Institute for Biological Functions, Chubu University, Kasugai, Aichi, Japan.
Young-Sil
YS
Lee
Byung-Yoon
BY
Cha
Kiyoto
K
Saito
Hiroshi
H
Yamakawa
Sun-Sil
SS
Choi
Kohji
K
Yamaguchi
Takayuki
T
Yonezawa
Toshiaki
T
Teruya
Kazuo
K
Nagai
Je-Tae
JT
Woo
D054392:Adipokines / Q000235:genetics; D052436:Adipose Tissue, White / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D047309:Flavones / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D051272:Glucose Transporter Type 1 / Q000235:genetics; D051275:Glucose Transporter Type 4 / Q000235:genetics; D006943:Hyperglycemia / Q000188:drug therapy*; D007333:Insulin Resistance; D051379:Mice; D008820:Mice, Obese; D009132:Muscles / Q000737:chemistry / Q000378:metabolism
D054392:Adipokines; D000975:Antioxidants; D047309:Flavones; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; C495678:Slc2a1 protein, mouse; C008661:nobiletin