EFFECT OF HYPOXIA ON INSULIN-SECRETION BY ISOLATED RAT AND CANINE ISLETS OF LANGERHANS
EFFECT OF HYPOXIA ON INSULIN-SECRETION BY ISOLATED RAT AND CANINE ISLETS OF LANGERHANS
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DOI：
10.2337/diabetes.42.1.12
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发表时间：
1993-01-01
期刊：
影响因子：
7.7
通讯作者：
YARMUSH, ML
中科院分区：
文献类型：
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作者：
DIONNE, KE;COLTON, CK;YARMUSH, ML
利用一种可控制氧分压（pO₂）且具有快速动态响应的微灌注装置，研究了氧分压降低到生理水平以下对分离的朗格汉斯胰岛葡萄糖刺激的胰岛素释放（GSIR）的影响。缺氧显著降低了胰岛素的第二相分泌。对较低氧分压的反应迅速且可逆。尽管不同胰岛制剂的稳定的常氧（pO₂ = 142 mmHg）第二相分泌率差异很大，但每种制剂的S(x)与S₁₄₂的比值可用一条单一曲线表示，该曲线随着pO₂的降低而持续下降。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%。在体外培养1周后，第二相分泌率的氧敏感性下降：1周后P₅₀为13 mmHg，培养2 - 5周后仍为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氧分压梯度有关，这导致胰岛细胞暴露于从周边到核心呈放射状降低的低氧分压水平。我们假设低氧分压对S的影响是通过β细胞能量储备的耗竭来体现的。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再血管化之前以及免疫隔离胰岛植入装置的有效性中起关键作用。
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 S(x) 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 13-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.