Abstract:
Islets of Langerhans are anatomically dispersed within the pancreas and exhibit regulatory coordination between islets in response to nutritional and inflammatory stimuli. However, within individual islets, there is also multi-faceted coordination of function between individual beta-cells, and between beta-cells and other endocrine and vascular cell types. This is mediated partly through circulatory feedback of the major secreted hormones, insulin and glucagon, but also by autocrine and paracrine actions within the islet by a range of other secreted products, including somatostatin, urocortin 3, serotonin, glucagon-like peptide-1, acetylcholine, and ghrelin. Their availability can be modulated within the islet by pericyte-mediated regulation of microvascular blood flow. Within the islet, both endocrine progenitor cells and the ability of endocrine cells to trans-differentiate between phenotypes can alter endocrine cell mass to adapt to changed metabolic circumstances, regulated by the within-islet trophic environment. Optimal islet function is precariously balanced due to the high metabolic rate required by beta-cells to synthesize and secrete insulin, and they are susceptible to oxidative and endoplasmic reticular stress in the face of high metabolic demand. Resulting changes in paracrine dynamics within the islets can contribute to the emergence of Types 1, 2 and gestational diabetes.
摘要:
朗格汉斯胰岛在解剖学上分散在胰腺内,并在对营养和炎症刺激的反应中表现出胰岛之间的调节协调。然而,在单个胰岛中,单个β细胞之间也有多方面的功能协调,以及β细胞和其他内分泌和血管细胞类型之间。这部分是通过主要分泌激素的循环反馈介导的,胰岛素和胰高血糖素,而且还通过一系列其他分泌产物在胰岛内的自分泌和旁分泌作用,包括生长抑素,尿皮质素3,血清素,胰高血糖素样肽-1,乙酰胆碱,还有ghrelin.它们的可用性可以通过周细胞介导的微血管血流调节在胰岛内进行调节。在小岛内,内分泌祖细胞和内分泌细胞在表型之间转分化的能力都可以改变内分泌细胞质量以适应改变的代谢环境,受胰岛内营养环境调节。由于β细胞合成和分泌胰岛素所需的高代谢率,最佳胰岛功能不稳定。面对高代谢需求,它们容易受到氧化和内质网应激的影响。胰岛内旁分泌动力学的变化可能导致1型、2型和妊娠期糖尿病的出现。