Ullsten Sara, Lau Joey, Carlsson Per-Ola
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
J Endocr Soc. 2019 Jun 17;3(8):1608-1616. doi: 10.1210/js.2019-00101. eCollection 2019 Aug 1.
Low-oxygenated and dormant islets with a capacity to become activated when needed may play a crucial role in the complex machinery behind glucose homeostasis. We hypothesized that low-oxygenated islets, when not functionally challenged, do not rapidly cycle between activation and inactivation but are a stable population that remain low-oxygenated. As this was confirmed, we aimed to characterize these islets with regard to cell composition, vascular density, and endocrine cell proliferation. The 2-nitroimidazole low-oxygenation marker pimonidazole was administered as a single or repeated dose to Wistar Furth rats. The stability of oxygen status of islets was evaluated by immunohistochemistry as the number of islets with incorporated pimonidazole adducts after one or repeated pimonidazole injections. Adjacent sections were evaluated for islet cell composition, vascular density, and endocrine cell proliferation. Single and repeated pimonidazole injections over an 8-hour period yielded accumulation of pimonidazole adducts in the same islets. An average of 30% of all islets was in all cases positively stained for pimonidazole adducts. These islets showed a similar endocrine cell composition as other islets but had lower vascular density and -cell proliferation. In conclusion, low-oxygenated islets were found to be a stable subpopulation of islets for at least 8 hours. Although they have previously been observed to be less functionally active, their islet cell composition was similar to that of other islets. Consistent with their lower oxygenation, they had fewer blood vessels than other islets. Notably, -cell regeneration preferentially occurred in better-oxygenated islets.
低氧且处于休眠状态、在需要时能够被激活的胰岛，可能在葡萄糖稳态背后的复杂机制中发挥关键作用。我们推测，未受到功能挑战时，低氧胰岛不会在激活和失活之间快速循环，而是一个保持低氧状态的稳定群体。这一推测得到证实时，我们旨在从细胞组成、血管密度和内分泌细胞增殖方面对这些胰岛进行特征描述。给Wistar Furth大鼠单次或重复注射2 - 硝基咪唑类低氧标记物匹莫硝唑。通过免疫组织化学方法，以单次或重复注射匹莫硝唑后含有匹莫硝唑加合物的胰岛数量来评估胰岛氧状态的稳定性。对相邻切片评估胰岛细胞组成、血管密度和内分泌细胞增殖情况。在8小时内单次和重复注射匹莫硝唑，均导致匹莫硝唑加合物在相同胰岛中积累。在所有情况下，平均30%的胰岛对匹莫硝唑加合物呈阳性染色。这些胰岛的内分泌细胞组成与其他胰岛相似，但血管密度较低，β细胞增殖较少。总之，发现低氧胰岛至少在8小时内是一个稳定的胰岛亚群。尽管之前观察到它们的功能活性较低，但其胰岛细胞组成与其他胰岛相似。与它们较低的氧合状态一致，它们的血管比其他胰岛少。值得注意的是，β细胞再生优先发生在氧合较好的胰岛中。
