High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin Resistance.
High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin Resistance.
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DOI：
10.1155/2016/9321395
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发表时间：
2016
影响因子：
4.3
通讯作者：
Yada T
中科院分区：
文献类型：
--
作者：
Nakata M;Zhang B;Yang Y;Okada T;Shintani N;Hashimoto H;Yada T
腺苷酸环化酶激活多肽（PACAP）作用于葡萄糖和能量代谢的多个过程。PACAP增强脂肪细胞中的胰岛素作用和胰腺β细胞的胰岛素释放，从而增强葡萄糖耐量。与器官水平的这些作用相反，PACAP敲除小鼠表现出对胰岛素的超敏反应。然而，这一明显的差异仍有待解决。我们的目的是阐明PACAP基因敲除小鼠抗糖尿病表型的机制。喂食高脂饮食（HFD）会损害野生型小鼠的胰岛素敏感性和葡萄糖耐量，而这些变化在PACAP基因敲除小鼠中被阻止。HFD还损害了野生型小鼠肝脏中胰岛素诱导的Akt磷酸化，但在PACAP缺失小鼠中没有。使用GeneFishing方法，HFD增加野生型小鼠肝脏中白细胞共同抗原相关（LAR）蛋白酪氨酸磷酸酶。沉默LAR恢复了HFD小鼠肝脏中的胰岛素信号传导。此外，在PACAP敲除小鼠中，HFD引起的LAR表达增加被阻止。HFD增加了野生型小鼠肝脏中三种PACAP受体之一的VPAC 1受体（VPAC 1-R）的表达。这些数据表明PACAP-VPAC 1-R信号传导诱导HFD小鼠肝脏中的LAR表达和胰岛素抵抗。VPAC 1-R的拮抗作用可以防止HFD诱导的肝脏胰岛素抵抗的进展，提供了一种新的抗糖尿病策略。
Pituitary adenylate cyclase-activating polypeptide (PACAP) acts on multiple processes of glucose and energy metabolism. PACAP potentiates insulin action in adipocytes and insulin release from pancreatic β-cells, thereby enhancing glucose tolerance. Contrary to these effects at organ levels, PACAP null mice exhibit hypersensitivity to insulin. However, this apparent discrepancy remains to be solved. We aimed to clarify the mechanism underlying the antidiabetic phenotype of PACAP null mice. Feeding with high-fat diet (HFD) impaired insulin sensitivity and glucose tolerance in wild type mice, whereas these changes were prevented in PACAP null mice. HFD also impaired insulin-induced Akt phosphorylation in the liver in wild type mice, but not in PACAP null mice. Using GeneFishing method, HFD increased the leukocyte common antigen-related (LAR) protein tyrosine phosphatase in the liver in wild type mice. Silencing of LAR restored the insulin signaling in the liver of HFD mice. Moreover, the increased LAR expression by HFD was prevented in PACAP null mice. HFD increased the expression of VPAC1 receptor (VPAC1-R), one of three PACAP receptors, in the liver of wild type mice. These data indicate that PACAP-VPAC1-R signaling induces LAR expression and insulin resistance in the liver of HFD mice. Antagonism of VPAC1-R may prevent progression of HFD-induced insulin resistance in the liver, providing a novel antidiabetic strategy.
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DOI：
10.1111/j.1749-6632.1998.tb11233.x
发表时间：
1998-01-01
期刊：
VIP, PACAP, AND RELATED PEPTIDES
影响因子：
--
作者：
Fahrenkrug, J;Hannibal, J
通讯作者：
Hannibal, J
影响因子：
2.5
作者：
Nakata, M;Kohno, D;Yada, T
通讯作者：
Yada, T
影响因子：
15.9
作者：
Ahmad, F;Azevedo, JL;Goldstein, BJ
通讯作者：
Goldstein, BJ
影响因子：
3.3
作者：
MOLLER, K;ZHANG, YZ;SUNDLER, F
通讯作者：
SUNDLER, F
刺激性室室核向AGRP神经元电路，驱动饥饿。
影响因子：
64.8
作者：
通讯作者：
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