Insulin Infusion Is Linked to Increased NPPC Expression in Muscle and Plasma C-type Natriuretic Peptide in Male Dogs.
Insulin Infusion Is Linked to Increased NPPC Expression in Muscle and Plasma C-type Natriuretic Peptide in Male Dogs.
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DOI：
10.1210/jendso/bvab088
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发表时间：
2021-07-01
影响因子：
4.1
通讯作者：
Coate KC
中科院分区：
文献类型：
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作者：
Gregory JM;Kraft G;Farmer B;Smith MS;LaNeve DC;Williams PE;Tomasek K;Su YR;Wilson CS;Thompson MD;Cherrington AD;Coate KC
本研究的目的是评估胰岛素刺激的基因在犬骨骼肌中的表达，特别关注NPPC基因，该基因编码c型利钠肽，这是心脏代谢功能的关键激素调节因子。4只有意识的狗接受了高胰岛素和血糖钳夹的研究。在基础和胰岛素刺激条件下采集骨骼肌活检和动脉血浆样本。对肌肉组织进行大量RNA测序，以鉴定这两种稳态条件下的差异表达基因。我们的研究结果表明，NPPC是骨骼肌中对胰岛素输注反应最高的基因，在基础和胰岛素刺激条件下增加了4倍。为了支持我们的RNA测序数据，我们发现血浆胰岛素浓度在基础上提高15倍会引起动脉血浆n端激素原c型利钠肽浓度增加2倍（P = 0.0001）。我们的数据提示胰岛素可能在刺激骨骼肌分泌c型利钠肽中起作用。在这种情况下，c型利钠肽可能以旁分泌方式促进肌肉-血管床串扰并增强胰岛素介导的血管舒张。这可能有助于提高胰岛素和葡萄糖的输送，特别是在餐后吸收状态。
The purpose of this study was to assess insulin-stimulated gene expression in canine skeletal muscle with a particular focus on NPPC, the gene that encodes C-type natriuretic peptide, a key hormonal regulator of cardiometabolic function. Four conscious canines underwent hyperinsulinemic, euglycemic clamp studies. Skeletal muscle biopsy and arterial plasma samples were collected under basal and insulin-stimulated conditions. Bulk RNA sequencing of muscle tissue was performed to identify differentially expressed genes between these 2 steady-state conditions. Our results showed that NPPC was the most highly expressed gene in skeletal muscle in response to insulin infusion, rising 4-fold between basal and insulin-stimulated conditions. In support of our RNA sequencing data, we found that raising the plasma insulin concentration 15-fold above basal elicited a 2-fold (P = 0.0001) increase in arterial plasma concentrations of N-terminal prohormone C-type natriuretic peptide. Our data suggest that insulin may play a role in stimulating secretion of C-type natriuretic peptide by skeletal muscle. In this context, C-type natriuretic peptide may act in a paracrine manner to facilitate muscle–vascular bed crosstalk and potentiate insulin-mediated vasodilation. This could serve to enhance insulin and glucose delivery, particularly in the postprandial absorptive state.