Stimulatory Effect of a Sulfonylurea Analogue and Its Polymer Conjugate on Insulin Secretion from Rat Islets
Stimulatory Effect of a Sulfonylurea Analogue and Its Polymer Conjugate on Insulin Secretion from Rat Islets
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磺酰脲类似物及其聚合物缀合物对大鼠胰岛胰岛素分泌的刺激作用
DOI：
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
S. W. Kim
中科院分区：
文献类型：
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作者：
A. Kikuchi;Y. Bae;S. W. Kim
合成了具有可聚合端基的磺酰脲（格列本脲类似物）。该单体与N，N-二甲基丙烯酰胺（DMAAm）共聚。通过将这些磺酰脲单体和共聚物加入正常大鼠胰岛培养物中并测量上清液中的胰岛素浓度来评价体外生物活性。磺酰脲类单体在葡萄糖浓度为50和100 mg/dL时对大鼠胰岛显示出刺激作用，与强效磺酰脲类药物格列本脲的刺激指数相当，而在葡萄糖浓度为200 mg/dL时未观察到任何作用。磺酰脲聚合物刺激胰岛分泌胰岛素在低葡萄糖浓度为50毫克/分升，其单体化合物的生物活性的80%。然而，在100和200 mg/dL葡萄糖浓度下，胰岛素分泌无显著刺激。由于表明磺酰脲类药物受体位于ATP敏感性K+通道的脂质相中，因此磺酰脲类药物在细胞膜脂质相中的增溶和扩散可能会影响磺酰脲类药物与其受体的相互作用。在磺酰脲聚合物的情况下，聚合物中的磺酰脲单元可以与其受体相互作用，如在50 mg/dL的葡萄糖浓度下增加的胰岛素分泌所示，但其相互作用在一定程度上会受到大的亲水性聚合物主链的干扰。因此，通过加入这种特定的磺酰脲聚合物，在较高的葡萄糖浓度下观察到胰岛素分泌的变化较小。
A sulfonylurea with a polymerizable end group (a glyburide analogue) was synthesized. This monomer was copolymerized with N, N‐dimethylacrylamide (DMAAm). In vitro bioactivity was evaluated by adding these sulfonylurea monomers and copolymers into normal rat islet cultures and measuring the insulin concentration in the supernatant. The sulfonylurea monomer showed a stimulatory effect on rat islets at glucose concentrations of 50 and 100 mg/dL, with equivalent stimulation indices for glyburide, the potent sulfonylurea drug, while no effect was observed at a glucose concentration of 200 mg/dL. The sulfonylurea polymer stimulated Langerhans islets to secrete insulin at a low glucose concentration of 50 mg/dL, with 80% bioactivity of its monomeric compound. However, at 100 and 200 mg/dL glucose concentrations, there was no significant stimulation in insulin secretion. Because it is suggested that the sulfonylurea receptors are located in the lipid phase on the ATP‐sensitive K+ channels, the solubilization of sulfonylurea into, and its diffusion through, the lipid phase in the cell membrane may affect the interactions of sulfonylurea with its receptors. In the case of the sulfonylurea polymer, the sulfonylurea unit in the polymer can interact with its receptor as can be seen by the increased insulin secretion at a glucose concentration of 50 mg/dL, but its interaction would be interfered with to some extent by a large hydrophilic polymer backbone. Thus, less change in insulin secretion was observed at higher glucose concentrations by the addition of this particular sulfonylurea polymer.
细胞质钙增加。
DOI：
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发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Nelson,TY;Gaines,KL;Rajan,AS;Berg,M;Boyd3rd,AE
通讯作者：
Boyd3rd,AE
DOI：
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发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Gaines,KL;Hamilton,S;Boyd3rd,AE
通讯作者：
Boyd3rd,AE