Myrsén-Axcrona U, Ekblad E, Sundler F
Department of Physiology and Neuroscience, Lund University Hospital, University of Lund, Sweden.
Regul Pept. 1997 Feb 26;68(3):165-75. doi: 10.1016/s0167-0115(96)02113-1.
It has been suggested that members of the neuropeptide Y (NPY) family of regulatory peptides [NPY, peptide YY (PYY) and pancreatic polypeptide (PP)] play an important role in the development of the endocrine pancreas. The development of rat endocrine pancreas from embryonic (E) day 12 until 30 days postpartum (P) was studied with emphasis on NPY, PYY and PP and their co-existence with insulin, glucagon and somatostatin using single and double immunostaining and in situ hybridization. Already at E12, PYY was detectable in small endocrine cell clusters and found to be co-localised with both insulin and glucagon, which at this stage occurred in the same cells. At E16 most of the insulin-immunoreactive (IR) cells were distinct from the glucagon/PYY-IR cells. Interestingly, at E16 NPY mRNA, and at E17 NPY immunoreactivity appeared in a few, scattered endocrine cells. Virtually all NPY-IR endocrine cells were insulin-producing beta cells. At E18 the endocrine cells started to form typical islets with centrally located insulin/NPY-IR cells surrounded by glucagon/PYY-IR cells. AT E20-E21, the vast majority of insulin-producing cells also expressed NPY. However, at birth (day 0) islet cell NPY mRNA was lacking. Postnatally the number and immunostaining intensity of NPY-IR islet cells rapidly declined, being non-detectable at P5. Cells containing PP immunoreactivity and PP mRNA were first detected at E21. The adult pattern of islet peptide distribution, with NPY confined to neuronal elements. PYY and PP exclusively in endocrine cells, was established at P5. The beta cell expression of NPY during the latter part of embryogenesis coincides with the prepartal glucocorticoid surge and with rapid islet cell replication and differentiation. This is compatible with steroid induction of NPY expression and with a role for NPY in the maturation of beta cells and their hormone release, which occurs in the immediate neonatal period.
有人提出，神经肽Y（NPY）调节肽家族成员[神经肽Y、肽YY（PYY）和胰多肽（PP）]在胰腺内分泌的发育中起重要作用。研究了大鼠胚胎期（E）第12天至产后30天（P）胰腺内分泌的发育情况，重点研究了神经肽Y、肽YY和胰多肽及其与胰岛素、胰高血糖素和生长抑素的共存情况，采用单免疫染色和双免疫染色以及原位杂交技术。在胚胎第12天，肽YY在小的内分泌细胞簇中即可检测到，并且发现它与胰岛素和胰高血糖素共定位，而在这个阶段，胰岛素和胰高血糖素存在于同一细胞中。在胚胎第16天，大多数胰岛素免疫反应性（IR）细胞与胰高血糖素/肽YY-IR细胞不同。有趣的是，在胚胎第16天，神经肽Y mRNA出现，在胚胎第17天，神经肽Y免疫反应性出现在少数散在的内分泌细胞中。几乎所有神经肽Y-IR内分泌细胞都是产生胰岛素的β细胞。在胚胎第18天，内分泌细胞开始形成典型的胰岛，中央为胰岛素/神经肽Y-IR细胞，周围为胰高血糖素/肽YY-IR细胞。在胚胎第20 - 21天，绝大多数产生胰岛素的细胞也表达神经肽Y。然而，出生时（第0天）胰岛细胞缺乏神经肽Y mRNA。出生后，神经肽Y-IR胰岛细胞的数量和免疫染色强度迅速下降，在出生后第5天无法检测到。含有胰多肽免疫反应性和胰多肽mRNA的细胞在胚胎第21天首次检测到。成年胰岛肽分布模式，即神经肽Y局限于神经元成分，肽YY和胰多肽仅存在于内分泌细胞中，在出生后第5天确立。胚胎发育后期β细胞中神经肽Y的表达与产前糖皮质激素激增以及胰岛细胞的快速复制和分化相一致。这与糖皮质激素诱导神经肽Y表达以及神经肽Y在β细胞成熟及其激素释放中的作用相一致，而β细胞激素释放发生在新生儿早期。
