Effects of β 3 -adrenoceptor activation on expression of pancreatic adrenoceptors and angiotensin II receptors in ApoE −/− mice
European Journal of Pharmacology(2015)
Abstract
Hyperlipidemia can be harmful to the pancreas and β3-adrenoceptor agonist can improve lipid metabolism disorder. We aimed to study the effects of β3-adrenoceptor activation on glucose, insulin and the expression of pancreatic adrenoceptors and angiotensin II receptors. Ten C57BL/6J mice at the age of 10 weeks served as normal control, and forty age-matched apolipoprotein E knockout (ApoE−/−) mice were randomly divided into hyperlipidaemia model group, low-dose and high-dose β3-adrenoceptor agonist group and β3-adrenoceptor antagonist group. After 26 weeks of high-fat diet, treatments were given for 12 weeks. Serum glucose and insulin levels in 48 weeks old mice were measured using an automatic biochemical detector. Quantitative rt-PCR and Western blot were used to analyze the mRNA and protein expression of α1A-, α2A-, β2-, β3-adrenoceptors and angiotensin II type 1 and type 2 receptors in pancreas. We found that β3-adrenoceptor agonist could decrease serum glucose and insulin levels in aged ApoE−/− mice (P<0.01) and down-regulate the expression of α1A-adrenoceptor and angiotensin II type 1 receptor which were significantly increased in model mice (P<0.05, P<0.01). Compared with the model mice, α2A-, β2-, β3-adrenoceptor and angiotensin II type 2 receptor expression were up-regulated in β3-adrenoceptor agonist treat mice (P<0.05, P<0.01). These results suggest that chronic β3-adrenoceptor activation regulated the expression of adrenoceptors and angiontensin II receptors towards contrary direction, which indicates that there are interactions between β3-adrenoceptor and subtypes of adrenoceptor and angiotensin II receptor, and these interactions may play a protective role in pancreas and improve glucose metabolism disorders.
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Key words
β3-adrenoceptor agonist,Glucose,Insulin,Adrenoceptor,Angiotensin II receptor
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