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腾讯登录Diabetes：揭示肽类药物或可治疗先天性高胰岛素血症
| 导读 | 一项在青少年和成年人中的研究发现了一种试验药具有治疗儿童胰岛机能亢进的潜在价值，胰岛机能亢进是一种罕见严重的疾病，由于机体中某些基因的突变可以引发胰岛素水平异常升高，对人体极具危害性。研究者在文章中揭示，这种肽类药物名为exendin-（9-39）可以控制血糖水平。相关研究成果刊登在了近日的国际杂志<em>Diabetes</em>上。
先天性的胰岛机能亢进（HI）病... |
一项在青少年和成年人中的研究发现了一种试验药具有治疗儿童胰岛机能亢进的潜在价值，胰岛机能亢进是一种罕见严重的疾病，由于机体中某些基因的突变可以引发胰岛素水平异常升高，对人体极具危害性。研究者在文章中揭示，这种肽类药物名为exendin-（9-39）可以控制血糖水平。相关研究成果刊登在了近日的国际杂志<em>Diabetes</em>上。
先天性的胰岛机能亢进（HI）病人中，突变可以破坏β胰岛素分泌细胞的功能，治疗某些HI病人的标准方法是药物二氮嗪，该药物可以通过打开β细胞的钾通道来控制胰岛素分泌水平，然而这种药物并不能用于治疗大多数HI病人，大多数病人中，突变可以阻止钾通道的打开。
当异常的β细胞仅仅存在于胰脏的不连续部分时，精准的手术便可以将其去除，从而至于疾病。然而在大约一半的先天性疾病患者中，异常的细胞分散于整个胰脏组织中，外壳收储无法进行操作。当前的研究中，研究者使用药物exendin-（9-39），其可以封堵β细胞类高血糖素多肽（GLP-1）激素受体的活性，目前，GLP-1受体是治疗糖尿病的一个药物靶点。
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在研究中包括9个项目，参与者年龄为15-47，都有先天性的胰岛机能亢进病症，在9项研究中，在禁食阶段药物可以控制血糖水平，exendin也可以控制β细胞的胰岛素分泌。研究者表示这项研究虽然没有着重于研究生化机制，但是研究结果为治疗HI提供了一些线索和思路。
编译自：<a title="" href="http://www.sciencedaily.com/releases/2012/08/120801165351.htm" target="_blank">Peptide Controls Blood Sugar in People With Congenital Hyperinsulinism, Pilot Study Suggests</a>
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<a title="" href="http://dx.doi.org/doi:10.2337/db12-0166" target="_blank">doi:10.2337/db12-0166</a>
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<br/><strong>GLP-1 Receptor Antagonist Exendin-(9-39) Elevates Fasting Blood Glucose Levels in Congenital Hyperinsulinism Owing to Inactivating Mutations in the ATP-Sensitive K+ Channel </strong><br/>
Andrew C. Calabria1, Changhong Li1,2, Paul R. Gallagher3, Charles A. Stanley1,2 and Diva D. De León1,2⇓
Infants with congenital hyperinsulinism owing to inactivating mutations in the KATP channel (KATPHI) who are unresponsive to medical therapy will require pancreatectomy to control the hypoglycemia. In preclinical studies, we showed that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion and corrects fasting hypoglycemia in SUR-1−/− mice. The aim of this study was to examine the effects of exendin-(9-39) on fasting blood glucose in subjects with KATPHI. This was a randomized, open-label, two-period crossover pilot clinical study. Nine subjects with KATPHI received either exendin-(9-39) or vehicle on two different days. The primary outcome was blood glucose; secondary outcomes were insulin, glucagon, and GLP-1. In all subjects, mean nadir blood glucose and glucose area under the curve were significantly increased by exendin-(9-39). Insulin-to-glucose ratios were significantly lower during exendin-(9-39) infusion compared with vehicle. Fasting glucagon and intact GLP-1 were not affected by treatment. In addition, exendin-(9-39) significantly inhibited amino acid–stimulated insulin secretion in pancreatic islets isolated from neonates with KATPHI. Our findings have two important implications: 1) GLP-1 and its receptor play a role in the regulation of fasting glycemia in KATPHI; and 2) the GLP-1 receptor may be a therapeutic target for the treatment of children with KATPHI.
<br/>来源：生物谷
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先天性的胰岛机能亢进（HI）病人中，突变可以破坏β胰岛素分泌细胞的功能，治疗某些HI病人的标准方法是药物二氮嗪，该药物可以通过打开β细胞的钾通道来控制胰岛素分泌水平，然而这种药物并不能用于治疗大多数HI病人，大多数病人中，突变可以阻止钾通道的打开。
当异常的β细胞仅仅存在于胰脏的不连续部分时，精准的手术便可以将其去除，从而至于疾病。然而在大约一半的先天性疾病患者中，异常的细胞分散于整个胰脏组织中，外壳收储无法进行操作。当前的研究中，研究者使用药物exendin-（9-39），其可以封堵β细胞类高血糖素多肽（GLP-1）激素受体的活性，目前，GLP-1受体是治疗糖尿病的一个药物靶点。
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在研究中包括9个项目，参与者年龄为15-47，都有先天性的胰岛机能亢进病症，在9项研究中，在禁食阶段药物可以控制血糖水平，exendin也可以控制β细胞的胰岛素分泌。研究者表示这项研究虽然没有着重于研究生化机制，但是研究结果为治疗HI提供了一些线索和思路。
编译自：<a title="" href="http://www.sciencedaily.com/releases/2012/08/120801165351.htm" target="_blank">Peptide Controls Blood Sugar in People With Congenital Hyperinsulinism, Pilot Study Suggests</a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201208/2012080300122278.jpg" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/doi:10.2337/db12-0166" target="_blank">doi:10.2337/db12-0166</a>
PMC:
PMID:
</div>
<div>
<br/><strong>GLP-1 Receptor Antagonist Exendin-(9-39) Elevates Fasting Blood Glucose Levels in Congenital Hyperinsulinism Owing to Inactivating Mutations in the ATP-Sensitive K+ Channel </strong><br/>
Andrew C. Calabria1, Changhong Li1,2, Paul R. Gallagher3, Charles A. Stanley1,2 and Diva D. De León1,2⇓
Infants with congenital hyperinsulinism owing to inactivating mutations in the KATP channel (KATPHI) who are unresponsive to medical therapy will require pancreatectomy to control the hypoglycemia. In preclinical studies, we showed that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion and corrects fasting hypoglycemia in SUR-1−/− mice. The aim of this study was to examine the effects of exendin-(9-39) on fasting blood glucose in subjects with KATPHI. This was a randomized, open-label, two-period crossover pilot clinical study. Nine subjects with KATPHI received either exendin-(9-39) or vehicle on two different days. The primary outcome was blood glucose; secondary outcomes were insulin, glucagon, and GLP-1. In all subjects, mean nadir blood glucose and glucose area under the curve were significantly increased by exendin-(9-39). Insulin-to-glucose ratios were significantly lower during exendin-(9-39) infusion compared with vehicle. Fasting glucagon and intact GLP-1 were not affected by treatment. In addition, exendin-(9-39) significantly inhibited amino acid–stimulated insulin secretion in pancreatic islets isolated from neonates with KATPHI. Our findings have two important implications: 1) GLP-1 and its receptor play a role in the regulation of fasting glycemia in KATPHI; and 2) the GLP-1 receptor may be a therapeutic target for the treatment of children with KATPHI.
<br/>来源：生物谷
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