A Lupinoside prevented fatty acid induced inhibition of insulin sensitivity in 3T3 L1 adipocytes.
The decrease in insulin sensitivity to target tissues or insulin resistance leads to type 2 diabetes mellitus, an insidious disease threatening global health. Numerous evidences made free fatty acids (FFAs) responsible for insulin resistance and type 2 diabetes. We demonstrate here that the damage of insulin acitivity by a free fatty acid, palmitate could be prevented by a lupinoside. An incubation of 3T3 L1 adipocytes with a FFA i.e. palmitate inhibited insulin stimulated uptake of (3)H-2 deoxyglucose (2 DOG) significantly. Addition of a lupinoside purified from Pueraria tuberosa, lupinoside PA(4) (LPA(4)) strongly prevented this inhibition. We then examined insulin signaling pathway where palmitate significantly inhibited insulin stimulated phosphorylation of Insulin receptor tyrosine kinase, IRS 1and PI3 kinase, PDK1 and Akt/PKB. LPA(4) rescued this inhibition of signaling molecule by palmitate. Insulin mediated translocation of Glut4, the glucose transporter in insulin target cells, was effectively blocked by palmitate while, LPA(4) waived this block. Administration of LPA(4) to nutritionally induced diabetic rats significantly reduced the increase in plasma glucose. All these indicate LPA(4) to be a potentially therapeutic agent for insulin resistance and type 2 diabetes.
Dey
Debleena
D
Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700032, India.
Pal
Bikash C
BC
Biswas
Tanushree
T
Roy
Sib Sankar
SS
Bandyopadhyay
Arun
A
Mandal
Swapan Kumar
SK
Giri
Bir Bhanu
BB
Bhattacharya
Samir
S
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D010168:Palmitates / Q000494:pharmacology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029908:Pueraria / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D051275:Glucose Transporter Type 4; D007328:Insulin; D010168:Palmitates; D010936:Plant Extracts; D011993:Recombinant Fusion Proteins; D012503:Saponins; C522988:lupinoside PA4; D049452:Green Fluorescent Proteins; D003847:Deoxyglucose