详细记录  
题名:IG20/MADD Plays a Critical Role in Glucose-Induced Insulin Secretion.
作者:LI LC; WANG Y; CARR R; HADDAD CS; LI Z; QIAN L; OBERHOLZER J; MAKER AV; WANG Q; PRABHAKAR BS;
来源:Diabetes. 2013 Dec 30. [ IF= 7.89 ] ]
URL :10.2337/db13-0707
日期:20140102
摘要:Pancreatic beta-cell dysfunction is a common feature of Type-2 diabetes. Earlier,
we had cloned IG20 cDNA from a human insulinoma and had shown that IG20/MADD can
encode six different splice isoforms that are differentially expressed and have
unique functions, but its role in beta-cell function was unexplored. To
investigate the role of IG20/MADD in beta-cell function we generated conditional
knockout (KMA1ko) mice. Deletion of IG20/MADD in beta-cells resulted in
hyperglycemia and glucose intolerance associated with reduced and delayed
glucose-induced insulin production. KMA1ko beta-cells were able to process
insulin normally, but had increased insulin accumulation and showed a severe
defect in glucose-induced insulin release. These findings indicated that
IG20/MADD plays a critical role in glucose-induced insulin release from
beta-cells and its functional disruption can cause Type-2 diabetes. The clinical
relevance of these findings is highlighted by recent reports of very strong
association of rs7944584 single nucleotide polymorphism (SNP) of IG20/MADD with
fasting hyperglycemia/diabetes. Thus, IG20/MADD could be a therapeutic target for
Type-2 diabetes, particularly in those with rs7944584 SNP.

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