Intraislet production of GLP-1 by activation of prohormone convertase 1/3 in pancreatic α-cells in mouse models of ß-cell regeneration.
Intraislet production of GLP-1 by activation of prohormone convertase 1/3 in pancreatic α-cells in mouse models of ß-cell regeneration.
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作者：
Kilimnik G;Kim A;Steiner DF;Friedman TC;Hara M
胰岛是一种高度血管化的微器官，不仅由β细胞组成，而且由多种细胞类型组成，如α-、δ-、胰多肽-和ε-细胞，它们共同调节葡萄糖稳态。我们最近提出了一个新的模型，新生儿胰岛形成小鼠的分裂过程中连续的内分泌细胞增殖的形式分支索状结构在胚胎和新生儿。在新生胰腺中存在沿着大血管的大的相互连接的胰岛结构的延伸，其在进一步发育时分离成更小的片段（即，胰岛），其最终通过内部增殖而变得更球形，如在成人胰腺中所见。α-细胞跨越发育中的胰腺中的这些细长的胰岛样结构，我们假设这些结构代表分裂位点并促进离散胰岛的最终形成。α细胞表达激素原转化酶2和1/3（分别为PC 2和PC 1/3），导致胰高血糖素前体加工成胰高血糖素样肽1，从而导致局部产生这种重要的β细胞生长因子。此外，虽然成人的α细胞基本上只表达PC 2，但在胰岛素抵抗的小鼠模型如妊娠、ob/ob、db/db和前驱糖尿病NOD小鼠中也观察到PC 1/3的显著活化，这可能是β细胞增殖的常见机制。我们的研究表明，α细胞对β细胞增殖以及胰岛内的内分泌细胞网络具有重要作用。
The islet of Langerhans is a highly vascularized micro-organ consisting of not only β-cells but multiple cell types such as α-, delta-, pancreatic polypeptide- and epsilon-cells that work together to regulate glucose homeostatis. We have recently proposed a new model of the neonatal islet formation in mice by a process of fission following contiguous endocrine cell proliferation in the form of branched cord-like structures in embryos and newborns. There exist large stretches of interconnected islet structures along large blood vessels in the neonatal pancreas, which, upon further development, segregate into smaller fragments (i.e., islets) that eventually become more spherical by internal proliferation as seen in the adult pancreas. α-cells span these elongated islet-like structures in the developing pancreas, which we hypothesize represent sites of fission and facilitate the eventual formation of discrete islets. The α-cells express both prohormone convertase 2 and 1/3 (PC2 and PC1/3, respectively), which resulted in the processing of the proglucagon precursor into glucagon-like peptide 1, thereby leading to local production of this important β-cell growth factor. Furthermore, while α-cells in the adult basically only express PC2, significant activation of PC1/3 is also observed in mouse models of insulin resistance such as pregnant, ob/ob, db/db and prediabetic NOD mice, which may be a common mechanism in proliferating β-cells. Our study suggests an important role of α-cells for β-cell proliferation and further for the endocrine cell network within an islet.
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影响因子：
2.2
作者：
Kim A;Miller K;Jo J;Kilimnik G;Wojcik P;Hara M
通讯作者：
Hara M
DOI：
10.1073/pnas.0308604100
发表时间：
2004-03-02
影响因子：
11.1
作者：
Prado, CL;Pugh-Bernard, AE;Sussel, L
通讯作者：
Sussel, L
影响因子：
7.7
作者：
Sreenan, S;Pick, AJ;Polonsky, KS
通讯作者：
Polonsky, KS
影响因子：
4.8
作者：
ROUILLE, Y;MARTIN, S;STEINER, DF
通讯作者：
STEINER, DF
影响因子：
3.7
作者：
Miller K;Kim A;Kilimnik G;Jo J;Moka U;Periwal V;Hara M
通讯作者：
Hara M