title: Effect of Natural Products on Commercial Oral Antidiabetic Drugs in Enhancing 2-Deoxyglucose Uptake by 3T3-L1 Adipocytes.
abstract: OBJECTIVE
  The management of diabetes with insulin and synthetic oral hypoglycemic drugs (OHDs) can produce serious side effects and in addition fails to prevent diabetes-related complications in many patients. A new diabetes management strategy is needed that is more effective and has fewer side effects.
  
  
  METHODS
  This paper analyzes the dose- and time-dependent effect of three phytochemicals: berberine, arecoline and vanillic acid, and two antidiabetic drugs: 2,4-thiazolidinedione (TZD) and metformin, on the uptake of 2-deoxyglucose (2DG) by 3T3-L1 adipocytes. The interactions of the phytochemicals with the OHDs were analyzed with isobolograms and the combination index.
  
  
  RESULTS
  TZD and berberine increased 2DG uptake by 3.3-fold (with respect to control) at 15 μM and 25 μM, respectively. The same concentrations of arecoline and vanillic acid increased 2DG uptake by 3.2-and 2.9-fold, respectively, when compared with the basal level. Berberine and arecoline acted synergistically with both the OHDs, whereas vanillic acid had an additive interaction with TZD and an antagonistic interaction with metformin. Arecoline significantly increased the translocation of GLUT4 via the PPAR(γ) pathway, whereas berberine and vanillic acid did this via the AMPK-dependent pathway.
  
  
  CONCLUSIONS
  These phytochemicals significantly reduced the expression of the enzymes involved in fatty acid and cholesterol synthesis, indicating that they might help prevent the secondary complications of diabetes. The current study suggests that berberine and arecoline could allow dosage reduction of OHDs, which could also lead to a reduction in the toxicity and side effects caused by OHDs.
authors.affiliation: Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India.
authors.forename: Pranav Kumar
authors.initials: PK
authors.lastname: Prabhakar
authors.forename: Mukesh
authors.initials: M
authors.lastname: Doble