Adaptive beta-cell Proliferation Is Severely Restricted With Advanced Age

作者：Rankin Matthew M; Kushner Jake A^*

来源：Diabetes, 2009, 58(6): 1365-1372.

DOI：10.2337/db08-1198

OBJECTIVE-Regeneration of the insulin-secreting beta-cells is a fundamental research goal that could benefit patients with either type 1 or type 2 diabetes. beta-Cell proliferation can be acutely stimulated by a variety of stimuli in young rodents. However, it is unknown whether this adaptive beta-cell regeneration capacity is retained into old age.
RESEARCH DESIGN AND METHODS-We assessed adaptive beta-cell proliferation capacity in adult mice across a wide range of ages with a variety Of stimuli: partial pancreatectomy, low-dose administration of the beta-cell toxin streptozotocin, and exendin-4, a glucagon-like peptide 1 (GLP-1) agonist. beta-Cell proliferation was measured by administration of 5-bromo-2'-deoxyuridine (BrdU) in the drinking water.
RESULTS-Basal beta-cell proliferation was severely decreased with advanced age. Partial pancreatectomy greatly Stimulated beta-cell proliferation in young mice but failed to increase beta-cell replication in old mice. Streptozotocin stimulated beta-cell replication in Young mice but had little effect in old mice. Moreover, administration of GLP-1 agonist exendin-4 stimulated beta-cell proliferation in Young but not in old mice. Surprisingly, adaptive beta-cell proliferation capacity was minimal after 12 months of age, which is early middle age for the adult mouse life span.
CONCLUSIONS-Adaptive beta-cell proliferation is severely restricted with advanced age in mice, whether stimulated by partial pancreatectomy, low-dose streptozotocin, or exendin-. Thus, beta-cells in middle-aged mice appear to be largely postmitotic. Young rodents may not faithfully model the regenerative capacity of beta-cells in mature adult mice. Diabetes 58:1365-1372, 2009

• 出版日期2009-6