Dionne K E, Colton C K, Yarmush M L
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139.
Diabetes. 1993 Jan;42(1):12-21. doi: 10.2337/diab.42.1.12.
The effect of pO2s reduced below physiological levels on GSIR by isolated islets of Langerhans was investigated with a microperifusion apparatus that provided control of pO2 and rapid dynamic response. Second-phase insulin secretion was reduced substantially by hypoxia. The response to lower pO2 was rapid and reversible. Although the steady, normoxic (pO2 = 142 mmHg) second-phase secretion rate varied widely from one islet preparation to another, the ratio of Sx to S142 for each preparation could be represented by a single curve that exhibited a continuous reduction with decreasing pO2. For rat islets perifused 1 day after isolation, the secretion rate was nearly 100% of the normoxic value at a pO2 of 60 mmHg, 50% at 27 mmHg (P50, the pO2 at which the S142 is reduced by 50%), and approximately 2% at 5 mmHg. Oxygen sensitivity of second-phase secretion rate declined after 1 wk of in vitro culture: P50 was 13 mmHg after 1 wk and remained at 10 mmHg after 2-5 wk of culture. Canine islets exhibited a P50 of 16 mmHg after 1 wk of culture. The reduction in insulin secretion is thought to be associated with the existence of pO2 gradients outside and inside the isolated islets, resulting in exposure of islet cells to low pO2 levels that decrease radially from the periphery to the core. We hypothesize that the effect of low pO2 on S is manifested through depletion of the energy stores of the beta-cells. The effect of hypoxia on S may be an important factor in some in vitro secretion studies and may play a critical role in the effectiveness of transplanted islets before their revascularization and of immunoisolated islet implantation devices.
利用一种能控制氧分压（pO₂）并具备快速动态响应功能的微量灌注装置，研究了将pO₂降低至生理水平以下对分离的胰岛葡萄糖刺激胰岛素释放（GSIR）的影响。缺氧会显著降低第二阶段胰岛素分泌。对较低pO₂的反应迅速且可逆。尽管稳定的常氧（pO₂ = 142 mmHg）第二阶段分泌率在不同的胰岛制备物之间差异很大，但每种制备物的Sx与S142的比值都可以用一条单一曲线表示，该曲线随着pO₂的降低呈现持续下降。对于分离后1天进行灌注的大鼠胰岛，在pO₂为60 mmHg时分泌率接近常氧值的100%，在27 mmHg时为50%（P50，即S142降低50%时的pO₂），在5 mmHg时约为2%。体外培养1周后，第二阶段分泌率的氧敏感性下降：培养1周后P50为13 mmHg，培养2 - 5周后保持在10 mmHg。犬胰岛在培养1周后P50为16 mmHg。胰岛素分泌的减少被认为与分离的胰岛内外存在pO₂梯度有关，导致胰岛细胞暴露于从周边到核心呈放射状降低的低pO₂水平。我们假设低pO₂对S的影响是通过β细胞能量储备的消耗来体现的。缺氧对S的影响可能是一些体外分泌研究中的一个重要因素，并且可能在移植胰岛血管再通之前以及免疫隔离胰岛植入装置的有效性方面发挥关键作用。
