Insulin Up-Regulates Natriuretic Peptide Clearance Receptor Expression in the Subcutaneous Fat Depot in Obese Subjects: A Missing Link between CVD Risk and Obesity?
Insulin Up-Regulates Natriuretic Peptide Clearance Receptor Expression in the Subcutaneous Fat Depot in Obese Subjects: A Missing Link between CVD Risk and Obesity?
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DOI：
10.1210/jc.2011-2839
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发表时间：
2012-05-01
影响因子：
5.8
通讯作者：
Rudovich, Natalia
中科院分区：
文献类型：
--
作者：
Pivovarova, Olga;Goegebakan, Oezlem;Rudovich, Natalia
背景：利钠肽（NP）调节心血管稳态并具有多种代谢特性。NP水平降低或“利钠障碍”是胰岛素抵抗的征兆，如中心性肥胖。在胰岛素抵抗的受试者中，观察到sc脂肪组织（SAT）中NP清除受体（NPRC）的表达增加。目的：我们假设胰岛素对脂肪组织中NP受体的表达有明显调节作用。设计和参与者：在157名受试者（108名2型糖尿病患者）的内脏脂肪组织（VAT）和SAT成对样本中测量了NPRA、NPRB和NPRC mRNA的表达。通过正糖-高胰岛素和高糖-高胰岛素钳夹实验研究胰岛素对SAT中NPR基因表达的影响。此外，我们还检测了胰岛素和葡萄糖对培养的人单核细胞和巨噬细胞中NPR表达的影响。结果：VAT中NPRA和NPRC基因表达量高于SAT (P < 0.01)，但只有NPRC基因表达量与空腹胰岛素水平呈正相关(r = 0.65, P = 0.04 × 10(-3)；和r = 0.54, P = 0.002，分别为增值税和SAT)。NPRB在2型糖尿病患者VAT中的表达低于SAT，也低于非糖尿病患者。在正常血糖和高血糖-高胰岛素钳夹期间，SAT中NPRC基因表达上调（P = 0.038和P = 0.048），在高糖和胰岛素处理的单核细胞中，NPRC基因表达上调（70.2%;P = 0.01），但在成熟巨噬细胞中，NPRC基因表达上调。结论：胰岛素增加了SAT中NPRC的表达，与循环葡萄糖浓度无关。因此，胰岛素可能通过上调肥胖中NPRC的表达来抑制循环NP，从而在高胰岛素血症和肥胖之间提供了一种新的联系。[J] .中华内分泌杂志，2012,31(5):379 - 379。
Context: Natriuretic peptides (NP) regulate cardiovascular homeostasis and have multiple metabolic properties. Decreased levels of NP or "natriuretic handicap" are signs of insulin resistance such as central obesity. Increased expression of NP clearance receptor (NPRC) in sc adipose tissue (SAT) was observed in insulin-resistant subjects.Objective: We hypothesized that insulin acutely regulates NP receptor expression in adipose tissue.Design and Participants: NPRA, NPRB, and NPRC mRNA expression was measured in paired samples of visceral adipose tissue (VAT) and SAT from 157 subjects (108 with type 2 diabetes). The effect of insulin on NPR gene expression in SAT was studied in euglycemic-hyperinsulinemic and hyperglycemic-hyperinsulinemic clamp experiments. Additionally, the effect of insulin and glucose on NPR expression in the culture of primary human monocytes and macrophages was tested.Results: NPRA and NPRC gene expression was higher in VAT compared with SAT (P < 0.01), but only NPRC gene expression strongly correlated with fasting insulin levels (r = 0.65, P = 0.04 x 10(-3); and r = 0.54, P = 0.002, for VAT and SAT, respectively). NPRB expression was lower in VAT than in SAT in subjects with type 2 diabetes and was lower compared with nondiabetic subjects. NPRC gene expression was up-regulated in SAT during both euglycemic- and hyperglycemic-hyperinsulinemic clamps (P = 0.038 and P = 0.048, respectively), and was increased in high glucose and insulin treatment in monocytes (70.2%; P = 0.01), but not in mature macrophages.Conclusion: Insulin increased expression of NPRC in SAT independently of circulating glucose concentrations. Thus, insulin might suppress circulating NP via up-regulation of NPRC expression in obesity, providing a novel link between hyperinsulinemia and obesity. (J Clin Endocrinol Metab 97: E731-E739, 2012)