Comparison of the metabolic effects of metformin and troglitazone on fructose-induced insulin resistance in male Sprague-Dawley rats.
OBJECTIVE
Insulin resistance is a hallmark of the development of type 2 diabetes. Metformin and troglitazone are oral antidiabetic agents used to reduce insulin resistance. The aim of this study was to compare the metabolic effects of these two drugs in fructose-induced insulin-resistant rodents.


METHODS
Male Sprague-Dawley rats were allocated to receive one of the following four treatments for 6 weeks: normal rat chow (control group, n = 7), high-fructose diet (fructose group, n = 7), high-fructose diet plus metformin (metformin group, n = 8), or high-fructose diet plus troglitazone (troglitazone group, n = 8). Systolic blood pressure (SBP), insulin, free fatty acid (FFA), and triglyceride concentrations were measured as parameters of insulin resistance. Leptin concentration was also measured in the four groups.


RESULTS
The fructose group developed significantly elevated SBP, hyperinsulinemia, and hypertriglyceridemia without significant change in body weight or leptin concentration compared with the control group. The metformin group had significantly reduced body weight (397.9 +/- 40.9 vs 470.1 +/- 59.6 g, p < 0.05), insulin concentration (14.8 +/- 10.5 vs 48.4 +/- 15.2 microU/mL, p < 0.05), triglyceride concentration (75.3 +/- 65.5 vs 250.1 +/- 95.7 mg/dL, p < 0.05), and leptin concentration (3.1 +/- 1.5 vs 6.9 +/- 2.0 ng/mL, p < 0.05) without significant change in SBP (147.8 +/- 5.8 vs 152.4 +/- 13.0 mm Hg, p > 0.05) compared with the fructose group. The troglitazone group had significantly reduced SBP (137.8 +/- 9.2 vs 152.4 +/- 13.0 mm Hg, p < 0.05), insulin concentration (15.0 +/- 13.6 vs 48.4 +/- 15.2 microU/mL, p < 0.05), FFA concentration (38.9 +/- 22.7 vs 78.7 +/- 24.6 mg/dL, p < 0.05), triglyceride concentration (67.6 +/- 32.4 vs 250.1 +/- 95.7 mg/dL, p < 0.05), and leptin concentration (4.4 +/- 2.0 vs 6.9 +/- 2.0 ng/mL, p < 0.05) without significant change in body weight (452.5 +/- 32.8 vs 470.1 +/- 59.6 g, p > 0.05) compared with the fructose group. The metabolic effects of metformin and troglitazone on insulin, FFA, triglyceride, and leptin concentrations were not significantly different. However, metformin treatment resulted in significantly lower body weight (397.9 +/- 40.9 vs 452.5 +/- 32.8 g) and troglitazone treatment in significantly lower SBP (137.8 +/- 9.2 vs 147.8 +/- 5.8 mm Hg) compared to the fructose group, after adjusting for basal values (p < 0.05).


CONCLUSIONS
Both metformin and troglitazone were comparably effective in reducing insulin resistance. Metformin treatment caused body weight reduction but was not effective in reducing SBP. Troglitazone treatment lowered SBP but did not reduce body weight.
Chen
C C
CC
Division of Endocrinology and Metabolism, Department of Medicine, China Medical College Hospital, 2 Yuh-Der Road, Taichung, Taiwan.
Wang
H J
HJ
Shih
H C
HC
Sheen
L Y
LY
Chang
C T
CT
Chen
R H
RH
Wang
T Y
TY
D000818:Animals; D002839:Chromans / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005632:Fructose / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D020738:Leptin; D013844:Thiazoles; D045162:Thiazolidinediones; D005632:Fructose; D008687:Metformin; D000077288:Troglitazone