title: Glucose uptake stimulatory potential and antidiabetic activity of the Arnebin-1 from Arnabia nobelis.
abstract: The enhanced disposal of glucose by the peripheral tissue is an important mechanism to regulate hyperglycemia. Here, we investigated the effect of Arnebin-1 from Arnebia nobilis, on glucose disposal in skeletal muscle cells and explored its in vivo antihyperglycemic potential. In L6 myotubes, Arnebin-1 stimulated glucose uptake, mediated through the enhanced translocation of the glucose transporter-4 (GLUT4) to plasma membrane, without changing the amount of GLUT4 or GLUT1. These effects of Arnebin-1 were synergistic with that of insulin. The effect of Arnebin-1 on glucose uptake was abolished in presence of wortmannin, and Arnebin-1 significantly stimulated the phosphorylation of Akt and downstream marker GSK-3β. Moreover, treatment with Arnebin-1 lowered postprandial blood glucose levels in streptozotocin-induced diabetic rats, and improved glucose tolerance and suppressed the rises in the fasting blood glucose, serum insulin, triglycerides, and total cholesterol in db/db mice, associated with enhanced expression of the major marker of the PI-3-Kinase-mediated signaling cascade in skeletal muscle. These findings suggest that Arnebin-1 exert antihyperglycemic activity through stimulating glucose disposal in peripheral tissues via PI-3-Kinase-dependent pathway.
authors: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors: Sukanya
authors: S
authors: Pandeti
authors: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors: Deepti
authors: D
authors: Arha
authors: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors: Akansha
authors: A
authors: Mishra
authors: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors: Sabbu Sathish
authors: SS
authors: Reddy
authors: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors: Arvind K
authors: AK
authors: Srivastava
authors: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India. Electronic address: t_narendra@cdri.res.in.
authors: Tadigoppula
authors: T
authors: Narender
authors: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India. Electronic address: akhilesh_tamrakar@cdri.res.in.
authors: Akhilesh K
authors: AK
authors: Tamrakar
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D028082:Boraginaceae / Q000737:chemistry*; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D007004:Hypoglycemic Agents; D009285:Naphthoquinones; C032573:beta, beta-dimethylacrylshikonin; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose
keywords: Arnabia nobelis; GLUT4 translocation; Glucose uptake; Insulin resistance; Skeletal muscle