Altered proinsulin conversion in rat pancreatic islets exposed long-term to various glucose concentrations or interleukin-1β
Altered proinsulin conversion in rat pancreatic islets exposed long-term to various glucose concentrations or interleukin-1β
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DOI：
10.1677/joe.1.06676
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发表时间：
2007-02-01
影响因子：
4
通讯作者：
Carlsson, Carina
中科院分区：
文献类型：
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作者：
Borjesson, Andreas;Carlsson, Carina
为了阐明P细胞功能与胰岛素原转化为胰岛素之间的可能关系，将分离的大鼠胰岛在各种葡萄糖浓度（5.6-56 mM）下在组织培养物中维持1周。还对用白细胞介素-1 β（IL-1 β）培养48小时的胰岛进行了研究。用脉冲追踪标记法和免疫沉淀法测定新合成的胰岛素原和胰岛素的相对含量。ELISA法检测培养液和胰岛内胰岛素和胰岛素原的含量。采用实时荧光定量PCR技术，研究了胰岛素原转化酶（PC 1和PC 2）的mRNA水平。在56 mM葡萄糖下培养的胰岛与在5.6 mM葡萄糖下培养的胰岛相比，在90分钟的追踪期后，新合成的胰岛素原的比例增加，然而，在11和28 mM葡萄糖下培养后没有观察到差异。ELISA测量显示，在增加的葡萄糖浓度下培养以及胰岛暴露于IL-1 β增加了培养基中胰岛素原的积累。在11和28 mM葡萄糖培养后，PC I的mRNA表达增加。与对照胰岛相比，用IL-1 β处理48 h在45和90 min时增加胰岛素原的比例。这些胰岛还显示出PC 1和PC 2的mRNA水平降低。胰岛素原半衰期的计算表明IL-1 β治疗后显著延长。我们得出结论，葡萄糖对胰岛的持续功能刺激与胰岛素原转化率降低有关，这对于用IL-1 β处理的胰岛也是如此。这可能有助于1型糖尿病和2型糖尿病发病时发现的胰岛素原水平升高。
In order to elucidate a possible relationship between P-cell function and conversion of proinsulin to insulin, isolated rat pancreatic islets were maintained in tissue culture for 1 week at various glucose concentrations (5.6-56 mM). Studies were also conducted on islets cultured for 48 h with interleukin-1 beta (IL-1 beta). By pulse-chase labelling and immunoprecipitation, the relative contents of newly synthesized proinsulin and insulin were determined. ELISA was used to analyse insulin and proinsulin content in medium and within islets. Using real-time PCR, the mRNA levels of proinsulin converting enzymes (PC1 and PC2) were studied. Islets cultured at 56 mM glucose had an increased proportion of newly synthesized proinsulin when compared with islets cultured at 5.6 mM glucose after a 90-min chase periods, however, no difference was observed after culture at I I and 28 mM glucose. ELISA measurements revealed that culture at increased glucose concentrations as well as islet exposure to IL-1 beta increased proinsulin accumulation in the culture media. The mRNA expression of PC I was increased after culture at 11 and 28 mM glucose. Treatment for 48 h with IL-1 beta increased the proportion of proinsulin both at 45 and 90 min when compared with control islets. These islets also displayed a decreased mRNA level of PC1 as well as PC2. Calculations of the half-time for proinsulin demonstrated a significant prolongation after treatment with IL-1 beta. We conclude that a sustained functional stimulation by glucose of islets is coupled to a decreased conversion of proinsulin which is also true for islets treated with IL-1 beta. This may contribute to the elevated levels of proinsulin found both at the onset of type 1 diabetes as well as in type 2 diabetes.