Stoffers D A, Kieffer T J, Hussain M A, Drucker D J, Bonner-Weir S, Habener J F, Egan J M
Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, USA.
Diabetes. 2000 May;49(5):741-8. doi: 10.2337/diabetes.49.5.741.
Diabetes is caused by a failure of the pancreas to produce insulin in amounts sufficient to meet the body's needs. A hallmark of diabetes is an absolute (type 1) or relative (type 2) reduction in the mass of pancreatic beta-cells that produce insulin. Mature beta-cells have a lifespan of approximately 48-56 days (rat) and are replaced by the replication of preexisting beta-cells and by the differentiation and proliferation of new beta-cells (neogenesis) derived from the pancreatic ducts. Here, we show that the insulinotropic hormone glucagon-like peptide (GLP)-1, which is produced by the intestine, enhances the pancreatic expression of the homeodomain transcription factor IDX-1 that is critical for pancreas development and the transcriptional regulation of the insulin gene. Concomitantly, GLP-1 administered to diabetic mice stimulates insulin secretion and effectively lowers their blood sugar levels. GLP-1 also enhances beta-cell neogenesis and islet size. Thus, in addition to stimulating insulin secretion, GLP-1 stimulates the expression of the transcription factor IDX-1 while stimulating beta-cell neogenesis and may thereby be an effective treatment for diabetes.
糖尿病是由胰腺无法分泌足够数量的胰岛素以满足身体需求所致。糖尿病的一个标志是产生胰岛素的胰腺β细胞数量绝对（1型糖尿病）或相对（2型糖尿病）减少。成熟的β细胞寿命约为48 - 56天（大鼠），并通过已存在的β细胞复制以及源自胰腺导管的新β细胞（新生）的分化和增殖来替代。在此，我们表明由肠道产生的促胰岛素激素胰高血糖素样肽（GLP）-1可增强同源域转录因子IDX-1在胰腺中的表达，该转录因子对胰腺发育及胰岛素基因的转录调控至关重要。同时，给糖尿病小鼠注射GLP-1可刺激胰岛素分泌并有效降低其血糖水平。GLP-1还可增强β细胞新生及胰岛大小。因此，除了刺激胰岛素分泌外，GLP-1在刺激β细胞新生的同时还能刺激转录因子IDX-1的表达，从而可能成为治疗糖尿病的有效方法。
