| Autor: |
Abe H; or Toyoyoshi Uchida, M.D., Ph.D., Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. hwatada@juntendo.ac.jp or uchitoyo@juntendo.ac.jp., Uchida T, Hara A, Mizukami H, Komiya K, Koike M, Shigihara N, Toyofuku Y, Ogihara T, Uchiyama Y, Yagihashi S, Fujitani Y, Watada H |
| Jazyk: |
angličtina |
| Zdroj: |
Endocrinology [Endocrinology] 2013 Dec; Vol. 154 (12), pp. 4512-24. Date of Electronic Publication: 2013 Oct 08. |
| DOI: |
10.1210/en.2013-1578 |
| Abstrakt: |
Autophagy is cellular machinery for maintenance of β-cell function and mass. The implication of autophagy failure in β-cells on the pathophysiology of type 2 diabetes and its relation to the effect of treatment of diabetes remains elusive. Here, we found increased expression of p62 in islets of db/db mice and patients with type 2 diabetes mellitus. Treatment with exendin-4, a glucagon like peptide-1 receptor agonist, improved glucose tolerance in db/db mice without significant changes in p62 expression in β-cells. Also in β-cell-specific Atg7-deficient mice, exendin-4 efficiently improved blood glucose level and glucose tolerance mainly by enhanced insulin secretion. In addition, we found that exendin-4 reduced apoptotic cell death and increased proliferating cells in the Atg7-deficient islets, and that exendin-4 counteracted thapsigargin-induced cell death of isolated islets augmented by autophagy deficiency. Our results suggest the potential involvement of reduced autophagy in β-cell dysfunction in type 2 diabetes. Without altering the autophagic state in β-cells, exendin-4 improves glucose tolerance associated with autophagy deficiency in β-cells. This is mainly achieved through augmentation of insulin secretion. In addition, exendin-4 prevents apoptosis and increases the proliferation of β-cells associated with autophagy deficiency, also without altering the autophagic machinery in β-cells. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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