Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Glucose Production via the Hepatic Sympathetic Innervation in Rats

被引：30

作者：

Yi, Chun-Xia ^{[1
]}

Sun, Ning ^{[1
,2
]}

Ackermans, Mariette T. ^{[3
]}

Alkemade, Anneke ^{[4
]}

Foppen, Ewout ^{[1
,4
]}

Shi, Jing ^{[2
]}

Serlie, Mireille J. ^{[4
]}

Buijs, Ruud M. ^{[5
]}

Fliers, Eric ^{[4
]}

Kalsbeek, Andries ^{[1
,4
]}

机构：

[1] Netherlands Inst Neurosci, Amsterdam, Netherlands

[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Neurobiol, Huazhong, Hubei, Peoples R China

[3] Univ Amsterdam, Acad Med Ctr, Dept Clin Chem Lab Endocrinol, NL-1105 AZ Amsterdam, Netherlands

[4] Univ Amsterdam, Acad Med Ctr, Dept Endocrinol & Metab, NL-1105 AZ Amsterdam, Netherlands

[5] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City, DF, Mexico

来源：

DIABETES | 2010年 / 59卷 / 07期

关键词：

VASOACTIVE INTESTINAL POLYPEPTIDE; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CENTRAL-NERVOUS-SYSTEM; HORMONE CRH GENE; SUPRACHIASMATIC NUCLEUS; VPAC(2) RECEPTOR; TISSUE DISTRIBUTION; PEPTIDE PACAP; EXPRESSION; NEURONS;

D O I：

10.2337/db09-1398

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVE-The unraveling of the elaborate brain networks that control glucose metabolism presents one of the current challenges in diabetes research. Within the central nervous system, the hypothalamus is regarded as the key brain area to regulate energy homeostasis. The aim of the present study was to investigate the hypothalamic mechanism involved in the hyperglycemic effects of the neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP). RESEARCH DESIGN AND METHODS-Endogenous glucose production (EGP) was determined during intracerebroventricular infusions of PACAP-38, vasoactive intestinal peptide (VIP), or their receptor agonists. The specificity of their receptors was examined by coinfusions of receptor antagonists. The possible neuronal pathway involved was investigated by 1) local injections in hypothalamic nuclei, 2) retrograde neuronal tracing from the thoracic spinal cord to hypothalamic preautonomic neurons together with Fos immunoreactivity, and 3) specific hepatic sympathetic or parasympathetic denervation to block the autonomic neuronal input to liver. LTS-Intracerebroventiicular infusion of PACAP-38 increased EGP to a similar extent as a VIP/PACAP-2 (VPAC2) receptor agonist, and intracerebroventricular administration of VIP had significantly less influence on EGP. The PACAP-38 induced increase of EGP was significantly suppressed by preinfusion of a VPAC2 but not a PAC1 receptor antagonist, as well as by hepatic sympathetic but not parasympathetic denervation. In the hypothalamus, Fos immunoreactivity induced by PACAP-38 was colocalized within autonomic neurons in paraventricular nuclei projecting to preganglionic sympathetic neurons in the spinal cord. Local infusion of PACAP-38 directly into the PVN induced a significant increase of EGP. CONCLUSIONS-This study demonstrates that PACAP-38 signaling via sympathetic preautonomic neurons located in the paraventricular nucleus is an important component in the hypothalamic control of hepatic glucose production. Diabetes 59: 1591-1600, 2010

引用

页码：1591 / 1600

页数：10

共 51 条

[1] The quantification of gluconeogenesis in healthy men by 2H2O and [2-13C]glycerol yields different results:: Rates of gluconeogenesis in healthy men measured with 2H2O are higher than those measured with [2-13C]glycerol [J].