Short-term pioglitazone treatment prevents free fatty acid-induced hepatic insulin resistance in normal rats: possible role of the resistin and adiponectin.
We have evaluated the effects of a 2 week treatment with pioglitazone (Pio, 4mg/kg x d) on hepatic and peripheral insulin sensitivity, plasma adiponectin, and resistin concentrations in lipid-infused rats. Lipid infusion caused a large (60% in 4h) decrease in whole-body insulin sensitivity. Hepatic and peripheral insulin resistance contributed about equally to the whole-body insulin resistance. Pio treatment significantly improved whole-body insulin sensitivity due to normalization of hepatic insulin action, whereas peripheral insulin action remained unchanged and inhibited. Basal plasma resistin levels were approximately 4-fold lower in Pio-treated than in untreated rats. During lipid infusion, resistin levels rose in both Pio-treated and untreated rats, but remained significantly lower in Pio-treated than in untreated rats (P<0.01). Dot-blot analyses revealed a marked decrease in resistin protein levels in the liver of Pio-treated rats. Resistin levels were higher in muscle tissue in lipid group compared with control and Pio-treated rats (P<0.05). Fasting plasma adiponectin levels were 1.5-fold higher in Pio-treated than in untreated rats. We conclude that short-term treatment of rats with Pio prevented lipid-induced hepatic insulin resistance and that Pio mediated lowering of blood resistin and raising of adiponectin levels may have contributed to that effect.
Yang
Gangyi
G
Department of Endocrinology, The Second Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 400010, China. gangyiyang@yahoo.com.cn
Li
Ling
L
Tang
Yi
Y
Boden
Guenther
G
D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D004347:Drug Interactions; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage*; D006493:Heparin / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D052243:Resistin / Q000097:blood*; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome
D052242:Adiponectin; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D052243:Resistin; D045162:Thiazolidinediones; D006493:Heparin; D000077205:Pioglitazone