Central Northern Adelaide Renal and Transplantation Services, South Australian and Northern Territory Islet Program and Australian Islet Consortium, Royal Adelaide Hospital, Adelaide, Australia.
Gen Comp Endocrinol. 2011 Nov 1;174(2):71-9. doi: 10.1016/j.ygcen.2011.07.004. Epub 2011 Jul 29.
The New world primates (NWP) Callithrix jacchus separated from man approximately 50 million years ago and is a potential alternative small non-human primate model for diabetes research. Ultrastructure, and gene expression of pancreatic islets and the recently described diabetes auto antigenic zinc transporters families in human, NWP and pig pancreas were studied. Morphologically NWP islets were larger than pig islets and similar in size to human islets. NWP islets alpha cells had high dense core surrounded by a limiting membrane, beta cells by the mixed morphology of the granule core, and delta cells by moderate opaque core. Antibody staining for insulin, glucagon, somatostatin and Glucagon-like peptide-1 (GLP-1) showed that the distribution pattern of the different cell types within islets was comparable to pig and human islets. In all three species protein expression of zinc transporter ZnT8 was detected in most of the insulin producing beta cells whereas Zip14 expression was widely expressed in alpha and beta cells. In both human and NWP little or no expression of Glut2 was observed compared to Glut1 and glucokinase at the protein level, however the messenger RNA level of Glut2 was greater than Glut1 and glucokinase. In contrast all three glucose transporters were expressed in pig islets at the protein level. The expression of Zip14 in islets is reported for the first time. In conclusion NWP pancreatic islets express comparable islet cell types and distribution to humans and pigs. Importantly, marmosets have a similar glucose transporter profile to humans, making this non-endangered primate species a useful animal model for pancreatic biology.
新世界灵长类动物(NWP)与人类分离约 5000 万年前,是糖尿病研究中潜在的替代小型非人类灵长类动物模型。研究了人类、NWP 和猪胰腺中的胰岛超微结构和基因表达,以及最近描述的糖尿病自身抗原锌转运体家族。从形态上看,NWP 的胰岛比猪的胰岛大,与人类的胰岛大小相似。NWP 的胰岛 alpha 细胞有高密度核心,周围有一个限界膜,beta 细胞有颗粒核心的混合形态,delta 细胞有中等不透明核心。胰岛素、胰高血糖素、生长抑素和胰高血糖素样肽-1(GLP-1)的抗体染色显示,不同细胞类型在胰岛内的分布模式与猪和人类的胰岛相似。在这三种物种中,锌转运体 ZnT8 的蛋白表达均在大多数胰岛素产生的 beta 细胞中检测到,而 Zip14 的表达在 alpha 和 beta 细胞中广泛表达。在人类和 NWP 中,与 Glut1 和葡萄糖激酶相比,在蛋白水平上观察到的 Glut2 表达很少或没有,然而 Glut2 的信使 RNA 水平大于 Glut1 和葡萄糖激酶。相比之下,所有三种葡萄糖转运体在猪胰岛中均在蛋白水平上表达。Zip14 在胰岛中的表达是首次报道。总之,NWP 的胰岛表达与人类和猪相似的胰岛细胞类型和分布。重要的是,狨猴具有与人类相似的葡萄糖转运体谱,使这种非濒危灵长类动物成为胰腺生物学的有用动物模型。