Abstract:
OBJECTIVE:The notion of combining immunomodulatory agents with the incretin exendin-4 (Ex-4) has seen considerable favor as a potential therapy for the reversal of type 1 diabetes in man. While the addition of Ex-4 provides modest improvement to the effectiveness of immunological-based monotherapies in reversing hyperglycemia in the nonobese diabetic (NOD) mouse, the mechanism of action underlying this effect remains controversial and formed the basis for this investigation. RESEARCH DESIGN AND METHODS:Female NOD mice with new onset diabetes received either Ex-4 (0.2 microg) or saline via daily intraperitoneal injection for 30 days. To maintain viability after diagnosis of diabetes, animals also received subcutaneous insulin pellets. When persistent hyperglycemia returned, animals were sacrificed and histological studies performed to assess beta-cell proliferation (BrdU+/insulin+; Ki67+/insulin+) and fractional insulin reactive area. RESULTS:Ex-4-treated animals experienced diabetes reversal rates no better than controls. Despite this, Ex-4-treated mice demonstrated increased fractional insulin area (P=.035) and beta-cell proliferation as evidenced by elevated BrdU (P=.0001) and Ki67 staining (P=.04) with insulin co-localization. Also noteworthy, Ex-4-treated mice had poor weight gain following diagnosis in comparison to saline-treated animals (P=.003). CONCLUSIONS:Ex-4 monotherapy (0.2 microg daily-10 microg/kg per day) in NOD mice with new onset diabetes increases beta-cell proliferation and fractional insulin area. Ex-4 remains a promising component of combination therapies for type 1 diabetes. Additional studies are needed to identify a dose that maximizes beta-cell proliferation and minimizes potential side effects.
journal_name
J Diabetes Complicationsjournal_title
Journal of diabetes and its complicationsauthors
Xue S,Wasserfall C,Parker M,McGrail S,McGrail K,Campbell-Thompson M,Schatz DA,Atkinson MA,Haller MJdoi
10.1016/j.jdiacomp.2008.12.004subject
Has Abstractpub_date
2010-05-01 00:00:00pages
163-7issue
3eissn
1056-8727issn
1873-460Xpii
S1056-8727(08)00124-4journal_volume
24pub_type
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journal_title:Journal of diabetes and its complications
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journal_title:Journal of diabetes and its complications
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更新日期:2015-11-01 00:00:00
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journal_title:Journal of diabetes and its complications
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journal_title:Journal of diabetes and its complications
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章
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更新日期:2020-12-01 00:00:00
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章
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journal_title:Journal of diabetes and its complications
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journal_title:Journal of diabetes and its complications
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journal_title:Journal of diabetes and its complications
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章,评审
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章
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journal_title:Journal of diabetes and its complications
pub_type: 临床试验,杂志文章
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journal_title:Journal of diabetes and its complications
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abstract::To clarify the influence of blood glucose level or diabetes mellitus on serum KL-6, a mucin-like glycoprotein, concentrations, they were measured against 176 diabetic subjects, including receiving insulin (INS) group (n=54), oral antidiabetics (OAD) group (n=78), and diet and exercise (D&E) group (n=44). Serum KL-6 co...
journal_title:Journal of diabetes and its complications
pub_type: 杂志文章
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journal_title:Journal of diabetes and its complications
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journal_title:Journal of diabetes and its complications
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章
doi:10.1016/j.jdiacomp.2008.04.003
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jdiacomp.2012.04.004
更新日期:2012-07-01 00:00:00
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章
doi:10.1016/j.jdiacomp.2011.03.002
更新日期:2011-07-01 00:00:00
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章
doi:10.1016/j.jdiacomp.2017.04.016
更新日期:2017-07-01 00:00:00
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章
doi:10.1016/s1056-8727(00)00145-8
更新日期:2001-03-01 00:00:00
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章,评审
doi:10.1016/j.jdiacomp.2017.06.003
更新日期:2017-09-01 00:00:00
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章
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更新日期:2016-08-01 00:00:00
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journal_title:Journal of diabetes and its complications
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更新日期:2014-05-01 00:00:00
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journal_title:Journal of diabetes and its complications
pub_type: 临床试验,杂志文章
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更新日期:1995-10-01 00:00:00
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章
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更新日期:2020-12-01 00:00:00
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journal_title:Journal of diabetes and its complications
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jdiacomp.2006.11.002
更新日期:2008-05-01 00:00:00