Free fatty acid-induced insulin resistance in the obese is not prevented by rosiglitazone treatment.
OBJECTIVE
Elevation of free fatty acids (FFAs) by the infusion of triglyceride-heparin emulsion infusion (TG-Hep) causes insulin resistance (IR). We examined the effect of insulin sensitizer (rosiglitazone) on FFA-induced IR.


METHODS
Nine obese subjects underwent a 6-h infusion of TG-Hep before and after 6 wk of rosiglitazone (8 mg/d) treatment. Hyperinsulinemic euglycemic clamps were performed during 0-2 and 4-6 h of TG-Hep.


RESULTS
After rosiglitazone for 6 wk, fasting FFA concentration fell, but not significantly (489 +/- 63 at 0 wk; 397 +/- 58 micromol/liter at 6 wk; P = 0.16), whereas C-reactive protein (4.26 +/- 0.95 at 0 wk; 2.03 +/- 0.45 microg/ml at 6 wk) and serum amyloid A (17.36 +/- 4.63 at 0 wk; 8.77 +/- 1.63 microg/ml at 6 wk) decreased significantly. At 0 wk, TG-Hep infusion caused a decrease in glucose infusion rate (GIR) from 4.49 +/- 0.95 mg/kg.min to 3.02 +/- 0.59 mg/kg.min (P = 0.018). Rosiglitazone treatment resulted in an increase in baseline GIR to 6.29 +/- 0.81 mg/kg.min (P = 0.03 vs. 0 wk), which decreased to 4.52 +/- 0.53 mg/kg.min (P = 0.001) after 6 h of TG-Hep infusion. The decrease in GIR induced by TG-Hep infusion was similar before and after rosiglitazone therapy [1.47 +/- 0.50 vs. 1.77 0.3 mg/kg.min (28.9 +/- 6.5 vs. 26.4 +/- 3.7%); P = 0.51]. The rise in FFAs and triglycerides after TG-Hep infusion was significantly lower at 6 wk (P = 0.006 for FFAs; P = 0.024 for triglycerides).


CONCLUSIONS
We conclude that rosiglitazone: 1) causes a significant increase in GIR; 2) induces a decrease in inflammatory mediators, C-reactive protein, and serum amyloid A; 3) decreases the rise in FFAs and triglycerides after TG-Hep infusion; and 4) does not prevent FFA-induced IR.
Dhindsa
Sandeep
S
Diabetes-Endocrinology Center of Western New York, Distinguished Chief of Endocrinology, State University of New York at Buffalo, 3 Gates Circle, Buffalo, New York 14209, USA.
Tripathy
Devjit
D
Sanalkumar
Nishanth
N
Ravishankar
Shreyas
S
Ghanim
Husam
H
Aljada
Ahmad
A
Dandona
Paresh
P
D000328:Adult; D002097:C-Reactive Protein / Q000037:antagonists & inhibitors; D004338:Drug Combinations; D004655:Emulsions; D005230:Fatty Acids, Nonesterified / Q000037:antagonists & inhibitors / Q000097:blood*; D005260:Female; D015309:Glucose Clamp Technique; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D007260:Infusion Pumps; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology*; D000077154:Rosiglitazone; D000685:Serum Amyloid A Protein / Q000037:antagonists & inhibitors; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014280:Triglycerides / Q000008:administration & dosage
D004338:Drug Combinations; D004655:Emulsions; D005230:Fatty Acids, Nonesterified; D000685:Serum Amyloid A Protein; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D006493:Heparin; D002097:C-Reactive Protein