Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
Peptides. 2020 Sep;131:170370. doi: 10.1016/j.peptides.2020.170370. Epub 2020 Jul 11.
Gut hormones affect cardiac function and contractility. In this study, we examined whether insulin affects the cardiac atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) gene expression and release of proANP-derived peptides in pigs. Anaesthetized pigs were included in an experimental study comparing the effect of hyperinsulinemia in 15 pigs submitted to two different protocols versus 11 control pigs receiving saline infusion. Phosphorylation of Akt on Thr308 was determined by western blotting with a pAkt-Thr308 antibody. The mRNA contents of ANP and BNP were determined with real-time PCR; plasma and cardiac tissue proANP was measured with an immunoluminometric assay targeted against the mid-region of the propeptide and a processing-independent assay. Insulin stimulation increased phosphorylation of Akt Thr308 in both left atrium and left ventricle of porcine hearts (p < 0.005). No change was observed in ANP and BNP mRNA contents in the right or left atrium. BNP mRNA contents in the left ventricle, however, decreased 3-fold (p = 0.02) compared to control animals, whereas the BNP mRNA content in the right ventricle as well as ANP mRNA content in the right and left ventricle did not change following hyperinsulinemia. Moreover, the peptide contents did not change in the four cardiac chambers. Finally, proANP concentrations in plasma did not change during the insulin infusion compared to the control animals. These results suggest that insulin does not have direct effect on atrial natriuretic peptide expression but may have a role in the left ventricle.
肠激素影响心脏功能和收缩性。在这项研究中,我们研究了胰岛素是否会影响心脏心钠肽 (ANP) 和 B 型利钠肽 (BNP) 基因的表达以及猪前心钠肽衍生肽的释放。在一项实验研究中纳入了麻醉猪,该研究比较了两种不同方案下高胰岛素血症对 15 头猪的影响,与接受生理盐水输注的 11 头对照猪相比。用 pAkt-Thr308 抗体通过 Western blot 测定 Akt 的 Thr308 磷酸化。用实时 PCR 测定 ANP 和 BNP 的 mRNA 含量;用针对前肽中段的免疫发光测定法和与加工无关的测定法测定血浆和心脏组织中 proANP 的含量。胰岛素刺激增加了猪心脏左心房和左心室中 Akt Thr308 的磷酸化(p<0.005)。在右心房或左心房中未观察到 ANP 和 BNP 的 mRNA 含量发生变化。然而,与对照动物相比,左心室中的 BNP mRNA 含量减少了 3 倍(p=0.02),而右心室中的 BNP mRNA 含量以及右和左心室中的 ANP mRNA 含量在高胰岛素血症后并未改变。此外,四个心腔中的肽含量没有变化。最后,与对照动物相比,胰岛素输注过程中血浆中 proANP 浓度没有变化。这些结果表明,胰岛素对心房利钠肽表达没有直接作用,但可能在左心室中起作用。