title: Deoxyandrographolide promotes glucose uptake through glucose transporter-4 translocation to plasma membrane in L6 myotubes and exerts antihyperglycemic effect in vivo.
abstract: Skeletal muscle is the principal site for postprandial glucose utilization and augmenting the rate of glucose utilization in this tissue may help to control hyperglycemia associated with diabetes mellitus. Here, we explored the effect of Deoxyandrographolide (DeoAn) isolated from the Andrographis paniculata Nees on glucose utilization in skeletal muscle and investigated its antihyperglycemic effect in vivo in streptozotocin-induced diabetic rats and genetically diabetic db/db mice. In L6 myotubes, DeoAn dose-dependently stimulated glucose uptake by enhancing the translocation of glucose transporter 4 (GLUT4) to cell surface, without affecting the total cellular GLUT4 and GLUT1 content. These effects of DeoAn were additive to insulin. Further analysis revealed that DeoAn activated PI-3-K- and AMPK-dependent signaling pathways, account for the augmented glucose transport in L6 myotubes. Furthermore, DeoAn lowered postprandial blood glucose levels in streptozotocin-induced diabetic rats and also suppressed the rises in the fasting blood glucose, serum insulin, triglycerides and LDL-Cholesterol levels of db/db mice. These findings suggest the therapeutic efficacy of the DeoAn for type 2 diabetes mellitus and can be potential phytochemical for its management.
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors.forename: Deepti
authors.initials: D
authors.lastname: Arha
authors.affiliation: Division of Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Sukanya
authors.initials: S
authors.lastname: Pandeti
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors.forename: Akansha
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Swayam Prakash
authors.initials: SP
authors.lastname: Srivastava
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Srivastava
authors.affiliation: Division of 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.forename: Tadigoppula
authors.initials: T
authors.lastname: Narender
authors.affiliation: 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.forename: Akhilesh Kumar
authors.initials: AK
authors.lastname: Tamrakar
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C114791:14-deoxyandrographolide; D004224:Diterpenes; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D019869:Phosphatidylinositol 3-Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: Andrographis paniculata; GLUT4 translocation; Glucose uptake; Insulin resistance; Skeletal muscle