Exendin-4 stimulates both β-cell replication and neogenesis, resulting in increased β-cell mass and improved glucose tolerance in diabetic rats
Exendin-4 stimulates both β-cell replication and neogenesis, resulting in increased β-cell mass and improved glucose tolerance in diabetic rats
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DOI：
10.2337/diabetes.48.12.2270
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发表时间：
1999-12-01
期刊：
影响因子：
7.7
通讯作者：
Bonner-Weir, S
中科院分区：
文献类型：
--
作者：
Xu, G;Stoffers, DA;Bonner-Weir, S
糖尿病是一种在普通人群中发病率不断增加且病因不明的疾病。糖尿病表现为由于胰腺β细胞产生胰岛素的相对不足而引起的高血糖症。糖尿病发展中的一个决定因素是绝对（1型，青少年糖尿病）或相对（2型，成年发病糖尿病）的β细胞质量不足。早些时候，我报道了肠激素胰高血糖素样肽I（GLP-I）有效地增加葡萄糖刺激的胰岛素分泌。在这里，我报告说，毒蜥外泌肽-4，一种长效GLP-1激动剂，刺激β细胞从导管祖细胞分化（新生）和β细胞的增殖时，给药大鼠。在2型糖尿病的部分胰腺切除大鼠模型中，胰腺切除术后每天施用exendin-4持续10天减弱糖尿病的发展。我们表明exendin-4通过β细胞的新生和增殖过程刺激胰腺的再生和β-cen质量的扩张。因此，GLP-1及其类似物有望作为一种新的疗法，当施用于β-细胞量减少的糖尿病个体时刺激β-细胞生长和分化。
Diabetes is a disease of increasing prevalence in the general population and of unknown cause. Diabetes is manifested as hyperglycemia due to a relative deficiency of the production of insulin by the pancreatic beta-cells. one determinant in the development of diabetes is an inadequate mass of beta-cells, either absolute (type 1, juvenile diabetes) or relative (type 2, maturity-onset diabetes). Earlier, me reported that the intestinal hormone glucagon-like peptide I (GLP-I) effectively augments glucose-stimulated insulin secretion. Here me report that exendin-4, a long-acting GLP-I agonist, stimulates both the differentiation of beta-cells from ductal progenitor cells (neogenesis) and proliferation of beta-cells when administered to rats. In a partial pancreatectomy rat model of type 2 diabetes, the daily administration of exendin-4 for 10 days post-pancreatectomy attenuates the development of diabetes, We show that exendin-4 stimulates the regeneration of the pancreas and expansion of beta-cen mass by processes of both neogenesis and proliferation of beta-cells. Thus, GLP-I and analogs thereof hold promise as a novel therapy to stimulate beta-cell growth and differentiation when administered to diabetic individuals with reduced beta-cell mass.