Effects of resistin expression on glucose metabolism and hepatic insulin resistance.
In order to observe the effect of increased serum resistin on glucose metabolism, insulin sensitivity, and hepatic insulin resistance (IR), mice were intravenously injected with recombinant adenovirus carrying the resistin gene (Adv-resistin-EGFP). Changes in hepatic glucose metabolism were observed using the Periodic Acid-Schiff method. Hepatic AMP-activated protein kinase (AMPK) activation was assessed by Western blot analysis, and glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was determined using real-time RT-PCR. Although no effect on fasting blood glucose was detected, increased fasting insulin levels, decreased glucose tolerance and insulin sensitivity, and reduced hepatic glycogen levels and AMPK activation were seen in the Adv-resistin-EGFP mice. Finally, elevated G6Pase and PEPCK mRNA expression levels were detected upon overexpression of resistin. Resistin may inhibit hepatic AMPK activity, which results in elevated expression of gluconeogenic enzymes thereby affecting glucose metabolism and leading to decreased glycogen storage that contributes to the development of hepatic IR.
Li
Fang-Ping
FP
Department of Endocrinology and Metabolism Department, The Second Affiliated Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou 510120, China. Amiy36@hotmail.com
He
Juan
J
Li
Zhi-Zhen
ZZ
Luo
Zhao-Fan
ZF
Yan
Li
L
Li
Yan
Y
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D004789:Enzyme Activation; D005215:Fasting; D015870:Gene Expression; D005822:Genetic Vectors; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance; D005952:Glucose-6-Phosphatase / Q000235:genetics; D006003:Glycogen / Q000032:analysis; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000235:genetics; D052243:Resistin / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D011994:Recombinant Proteins; D052243:Resistin; D006003:Glycogen; D055372:AMP-Activated Protein Kinases; D005952:Glucose-6-Phosphatase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose