Mig6 haploinsufficiency protects mice against streptozotocin-induced diabetes.
Mig6 haploinsufficiency protects mice against streptozotocin-induced diabetes.
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Mig6 单倍体不足可保护小鼠免受链脲佐菌素诱导的糖尿病。
DOI：
10.1007/s00125-014-3311-z
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发表时间：
2014-10
期刊：
影响因子：
8.2
通讯作者：
Fueger, Patrick T.
中科院分区：
文献类型：
--
作者：
Chen, Yi-Chun;Colvin, E. Scott;Griffin, Katherine E.;Maier, Bernhard F.;Fueger, Patrick T.
EGF and gastrin co-administration reverses type 1 diabetes in rodent models. However, the failure of this to translate into a clinical treatment suggests that EGF-mediated tissue repair is a complicated process and warrants further investigation. Thus, we aimed to determine whether EGF receptor (EGFR) feedback inhibition by mitogen-inducible gene 6 protein (MIG6) limits the effectiveness of EGF therapy and promotes type 1 diabetes development. We treated Mig6 (also known as Errfi1) haploinsufficient mice (Mig6+/−) and their wild-type littermates (Mig6+/+) with multiple low doses of streptozotocin (STZ), and monitored diabetes development via glucose homeostasis tests and histological analyses. We also investigated MIG6-mediated cytokine-induced desensitisation of EGFR signalling and the DNA damage repair response in 832/13 INS-1 beta cells. Whereas STZ-treated Mig6+/+ mice became diabetic, STZ-treated Mig6+/− mice remained glucose tolerant. In addition, STZ-treated Mig6+/− mice exhibited preserved circulating insulin levels following a glucose challenge. As insulin sensitivity was similar between Mig6+/− and Mig6+/+ mice, the preserved glucose tolerance in STZ-treated Mig6+/− mice probably results from preserved beta cell function. This is supported by elevated Pdx1 and Irs2 mRNA levels in islets isolated from STZ-treated Mig6+/− mice. Conversely, MIG6 overexpression in isolated islets compromises glucose-stimulated insulin secretion. Studies in 832/13 cells suggested that cytokine-induced MIG6 hinders EGFR activation and inhibits EGF-mediated DNA damage repair. STZ-treated Mig6+/− mice also have increased beta cell mass recovery. Reducing Mig6 expression promotes beta cell repair and abates the development of experimental diabetes, suggesting that MIG6 may be a novel therapeutic target for preserving beta cells.
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DOI：
10.1083/jcb.201002032
发表时间：
2010-05-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Frosi Y;Anastasi S;Ballarò C;Varsano G;Castellani L;Maspero E;Polo S;Alemà S;Segatto O
通讯作者：
Segatto O
影响因子：
7.7
作者：
Keenan HA;Sun JK;Levine J;Doria A;Aiello LP;Eisenbarth G;Bonner-Weir S;King GL
通讯作者：
King GL
影响因子：
5.3
作者：
Fiorentino, L;Pertica, C;Segatto, O
通讯作者：
Segatto, O
影响因子：
8.2
作者：
Meier, JJ;Ritzel, RA;Butler, PC
通讯作者：
Butler, PC
影响因子：
7.7
作者：
Evans-Molina, Carmella;Garmey, James C.;Mirmira, Raghavendra G.
通讯作者：
Mirmira, Raghavendra G.