Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model.
Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model.
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作者：
Richards P;Parker HE;Adriaenssens AE;Hodgson JM;Cork SC;Trapp S;Gribble FM;Reimann F
胰高血糖素样肽-1（GLP-1）是一种广泛参与代谢的肠道激素。基于GLP-1的治疗非常有效，因为它们增加了2型糖尿病患者的葡萄糖依赖性胰岛素分泌，但许多报告表明GLP-1对其他组织（包括心脏、血管系统、外分泌胰腺、肝脏和中枢神经系统）具有额外的有益作用，或在某些情况下具有潜在的危险作用。确定哪些组织表达GLP-1受体（GLP 1 R）对于开发基于GLP-1的治疗至关重要。我们的目的是使用不依赖于GLP 1 R抗体的方法鉴定和鉴定小鼠中GLP-1的靶点。使用新产生的glp 1 r-cre小鼠与荧光报告菌株杂交，我们发现glp 1 r表达的主要部位包括胰腺β和δ细胞、血管平滑肌、心房、胃窦/幽门、肠神经元以及迷走神经和背根神经节。在中枢神经系统，glp 1 r荧光细胞主要分布于最后区、弓状核、室旁核和下丘脑腹内侧核。胰腺导管内可见散在的glp 1 r荧光细胞。在心室肌细胞中未观察到glp 1 r荧光。GLP-1可激活GLP 1 r阳性肠神经元和迷走神经元，并可能促进肠道和中枢对局部释放GLP-1的反应，如调节肠道分泌运动活性和食欲。
Glucagon-like peptide-1 (GLP-1) is an intestinal hormone with widespread actions on metabolism. Therapies based on GLP-1 are highly effective because they increase glucose-dependent insulin secretion in people with type 2 diabetes, but many reports suggest that GLP-1 has additional beneficial, or in some cases potentially dangerous, actions on other tissues, including the heart, vasculature, exocrine pancreas, liver and central nervous system. Identifying which tissues express the GLP-1 receptor (GLP1R) is critical for the development of GLP-1 based therapies. Our objective was to identify and characterise the targets of GLP-1 in mice, using a method independent of GLP1R antibodies. Using newly-generated glp1r-cre mice crossed with fluorescent reporter strains, we show that major sites of glp1r expression include pancreatic β and δ-cells, vascular smooth muscle, cardiac atrium, gastric antrum/pylorus, enteric neurones and vagal and dorsal root ganglia. In the central nervous sytem, glp1r-fluorescent cells were abundant in the area postrema, arcuate nucleus, paraventricular nucleus and ventromedial hypothalamus. Sporadic glp1r-fluorescent cells were found in pancreatic ducts. No glp1r-fluorescence was observed in ventricular cardiomyocytes. Glp1r-positive enteric and vagal neurons were activated by GLP-1, and may contribute to intestinal and central responses to locally-released GLP-1, such as regulation of intestinal secretomotor activity and appetite.
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影响因子：
3.3
作者：
Llewellyn-Smith, I. J.;Reimann, F.;Gribble, F. M.;Trapp, S.
通讯作者：
Trapp, S.
影响因子：
8.2
作者：
Nachnani, J. S.;Bulchandani, D. G.;Alba, L. M.
通讯作者：
Alba, L. M.
影响因子：
4.8
作者：
Hansen, L;Deacon, CF;Holst, JJ
通讯作者：
Holst, JJ
影响因子：
29
作者：
Reimann F;Habib AM;Tolhurst G;Parker HE;Rogers GJ;Gribble FM
通讯作者：
Gribble FM
影响因子：
8.2
作者：
de Heer, J.;Rasmussen, C.;Holst, J. J.
通讯作者：
Holst, J. J.