The hypoglycaemic activity of fenugreek seed extract is mediated through the stimulation of an insulin signalling pathway.
The in vivo hypoglycaemic activity of a dialysed fenugreek seed extract (FSE) was studied in alloxan (AXN)-induced diabetic mice and found to be comparable to that of insulin (1.5 U kg(-1)). FSE also improved intraperitoneal glucose tolerance in normal mice. The mechanism by which FSE attenuated hyperglycaemia was investigated in vitro. FSE stimulated glucose uptake in CHO-HIRc-mycGLUT4eGFP cells in a dose-dependent manner. This effect was shown to be mediated by the translocation of glucose transporter 4 (GLUT4) from the intracellular space to the plasma membrane. These effects of FSE on GLUT4 translocation and glucose uptake were inhibited by wortmannin, a phosphatidylinositol 3-kinase (PI3-K) inhibitor, and bisindolylmaleimide 1, a protein kinase C (PKC)-specific inhibitor. In vitro phosphorylation analysis revealed that, like insulin, FSE also induces tyrosine phosphorylation of a number of proteins including the insulin receptor, insulin receptor substrate 1 and p85 subunit of PI3-K, in both 3T3-L1 adipocytes and human hepatoma cells, HepG2. However, unlike insulin, FSE had no effect on protein kinase B (Akt) activation. These results suggest that in vivo the hypoglycaemic effect of FSE is mediated, at least in part, by the activation of an insulin signalling pathway in adipocytes and liver cells.
Vijayakumar
Maleppillil Vavachan
MV
National Centre for Cell Science, NCCS Complex, Pune University Campus, Ganeshkhind, India.
Singh
Sandeep
S
Chhipa
Rishi Raj
RR
Bhat
Manoj Kumar
MK
D016475:3T3 Cells; D000496:Alloxan; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D045744:Cell Line, Tumor; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction; D029910:Trigonella / Q000737:chemistry*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D000496:Alloxan; D011493:Protein Kinase C