Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob mice. 2010

Young-Sil Lee, and Byung-Yoon Cha, and Kiyoto Saito, and Hiroshi Yamakawa, and Sun-Sil Choi, and Kohji Yamaguchi, and Takayuki Yonezawa, and Toshiaki Teruya, and Kazuo Nagai, and Je-Tae Woo
Research Institute for Biological Functions, Chubu University, Kasugai, Aichi, Japan.

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.

UI MeSH Term Description Entries
D007333 Insulin Resistance Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. Insulin Sensitivity,Resistance, Insulin,Sensitivity, Insulin
D008820 Mice, Obese Mutant mice exhibiting a marked obesity coupled with overeating, hyperglycemia, hyperinsulinemia, marked insulin resistance, and infertility when in a homozygous state. They may be inbred or hybrid. Hyperglycemic Mice,Obese Mice,Mouse, Hyperglycemic,Mouse, Obese,Hyperglycemic Mouse,Mice, Hyperglycemic,Obese Mouse
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006943 Hyperglycemia Abnormally high BLOOD GLUCOSE level. Postprandial Hyperglycemia,Hyperglycemia, Postprandial,Hyperglycemias,Hyperglycemias, Postprandial,Postprandial Hyperglycemias
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000975 Antioxidants Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D047309 Flavones A group of 4-keto-FLAVONOIDS. 2-Phenyl-2-Ene-Benzopyran-4-One Compounds
D051272 Glucose Transporter Type 1 A ubiquitously expressed glucose transporter that is important for constitutive, basal GLUCOSE transport. It is predominately expressed in ENDOTHELIAL CELLS and ERYTHROCYTES at the BLOOD-BRAIN BARRIER and is responsible for GLUCOSE entry into the BRAIN. Erythrocyte Glucose Transporter,GLUT-1 Protein,GLUT1 Protein,SLC2A1 Protein,Solute Carrier Family 2, Facilitated Glucose Transporter, Member 1 Protein,GLUT 1 Protein,Glucose Transporter, Erythrocyte
D051275 Glucose Transporter Type 4 A glucose transport protein found in mature MUSCLE CELLS and ADIPOCYTES. It promotes transport of glucose from the BLOOD into target TISSUES. The inactive form of the protein is localized in CYTOPLASMIC VESICLES. In response to INSULIN, it is translocated to the PLASMA MEMBRANE where it facilitates glucose uptake. GLUT-4 Protein,GLUT4 Protein,Insulin-Responsive Glucose Transporter,SLC2A4 Protein,Solute Carrier Family 2, Facilitated Glucose Transporter, Member 4 Protein,GLUT 4 Protein,Glucose Transporter, Insulin-Responsive,Insulin Responsive Glucose Transporter

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