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| Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats |
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| Author(s): Xu G, Stoffers DA, Habener JF, Bonner-Weir S |
| Source: DIABETES Volume: 48 Issue: 12 Pages: 2270-2276 Published: DEC 1999 |
| Times Cited: 447 References: 31 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Bonner-Weir, S (reprint author), Joslin Diabet Ctr, Elliott P Joslin Res Labs, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA |
Addresses:
1. Joslin Diabet Ctr, Elliott P Joslin Res Labs, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA
2. Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp,Labs Mol Endocrinol, Boston, MA 02115 USA |
| Publisher: AMER DIABETES ASSOC, 1660 DUKE ST, ALEXANDRIA, VA 22314 USA |
| Subject Category: Endocrinology & Metabolism |
| IDS Number: 259EE |
| ISSN: 0012-1797 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |