保护胰岛功能及促进胰岛再生临床治疗分析.ppt

* 在Zucker糖尿病肥胖（ZDF）大鼠中研究了静脉输注GLP-1对血糖控制和胰岛细胞的影响, Zucker糖尿病肥胖（ZDF）大鼠是一种糖尿病动物模型，当它的beta细胞增殖速度不能代偿beta细胞死亡（凋亡）速度时发生糖尿病. 糖尿病大鼠在第一天时接受2天的人重组GLP-1（n=8）或生理盐水(n=8)输注；在第六天时，接受葡萄糖耐量试验，在第七天时，它们被杀死并取出胰腺组织（每组从4只大鼠中获取胰腺切片），研究者继而对GLP-1对胰岛细胞团块、beta细胞增殖以及beta细胞凋亡的的作用进行研究.1 静脉输注 GLP-1 能够显著降低血糖水平 (p0.01) ，显著增加beta细胞体积1.6倍 (p0.01). GLP-1对beta细胞团块的影响显示与对照组相比，它可以使beta细胞增殖（活性分离的beta细胞数量）升高1.4倍(p0.05) ，beta细胞凋亡（凋亡beta细胞的数量）降低3.6倍 (p0.001). 研究的作者总结出GLP-1通过抑制胰岛细胞凋亡，促进胰岛细胞增殖改善ZDF大鼠的糖耐量.1 Reference Farilla L, Hui H, Bertolotto C et al. Glucagon-like peptide-1 promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats. Endocrinology 2002;143:4397–4408. * References 1. Deacon CF, Nauck MA, Toft-Nielsen M et al. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 1995;44:1126–1131. 2. Kieffer TJ, McIntosh CHS, Pederson RA. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 1995;136:3585–3596. 3. Vilsb?ll T, Krarup T, Deacon CF et al. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 2001;50:609–613. 4. Ahrén B. Gut peptides and type 2 diabetes mellitus treatment. Curr Diab Rep 2003;3:365–372. 5. Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab 1995;80:952–957. Weber AE. Dipeptidyl peptidase IV inhibitors for the treatment of diabetes. J Med Chem 2004;47:4135–4141. Drucker DJ. Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes. Expert Opin Investig Drugs 2003;12:87–100. Pospisilik JA, Stafford SG, Demuth H-U et al. Long-term treatment with the dipeptidyl peptidase IV