保护胰岛功能和促进胰岛的再生临床治疗.ppt

* 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 inhibitor P32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and beta-cell glucose responsiveness in VDF (fa/fa) Zucker rats. Diabetes 2002;51:943–950. After its release from L cells in the distal gut (ileum and the colon), GLP-1 is rapidly degraded by the enzyme DPP-4.1,2 DPP-4 is located in sites such as intestinal and renal brush borders as well as on the capillary surfaces and in a soluble form in plasma.3 DPP-4 cleaves two N-terminal amino acid residues from GLP-1 (7–36).4-6 The N-terminally truncated peptide GLP-1 (9–36) has no insulinotropic activity.3 Like GLP-1, GIP (1–42) is degrade