Open AccessThe Adipose Tissue Endocrine Mechanism of the Prophylactic Protective Effect of Pioglitazone in High-Fat Diet-Induced Insulin Resistance
Author(s) -
Yan Gong,
J Li,
C Li,
Yiming Mu,
Yuanyuan Xiao,
Hui Tian,
Changyu Pan,
Y Liu
Publication year - 2012
Publication title -
journal of international medical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.421
H-Index - 57
eISSN - 1473-2300
pISSN - 0300-0605
DOI - 10.1177/147323001204000409
Subject(s) - pioglitazone , medicine , insulin resistance , adipose tissue , endocrine system , insulin , endocrinology , mechanism (biology) , diabetes mellitus , type 2 diabetes , hormone , philosophy , epistemology
OBJECTIVE: To explore the adipose tissue endocrine mechanism of pioglitazone and its possible prophylactic role in insulin resistance. METHODS: Male Wistar rats were randomized to receive a normal diet (N group), a high-fat insulin resistance-inducing diet (IR group), or a high-fat diet plus treatment with pioglitazone (P group). Glucose tolerance and insulin resistance were tested at weeks 10 and 11 after starting the diet and, at week 12, adipose, liver and skeletal muscle tissue samples were taken. HepG2 cells were cultured with palmitic acid (PA), pioglitazone and PA plus pioglitazone, and RNA interference was used to downregulate adiponectin receptor (AdipoR) 2 in these cells. The mRNA and protein levels of adipokines (resistin and adiponectin), AdipoR1 and 2 and uptake of [ 3 H]-labelled glucose were measured in the HepG2 cells. RESULTS: Resistin and adiponectin in adipose tissue and AdipoR2 in liver tissue were significantly decreased in the IR group compared with the N group. Adiponectin and AdipoR2 were significantly increased and insulin resistance significantly decreased in the P group versus the IR group. In HepG2 cells, AdipoR2 levels and glucose uptake decreased significantly when PA was ≥ 200 μM, but were elevated by pioglitazone. Small interfering RNA-AdipoR2 confirmed glucose uptake in liver was regulated by AdipoR2. CONCLUSIONS: Pioglitazone prevented insulin resistance in rats fed a high-fat diet. Liver AdipoR2-mediated glucose uptake is important in the prophylactic effect of pioglitazone on insulin resistance.