Insulin Therapy for Gestational Diabetes Mellitus Does Not Fully Protect Offspring From Diet-Induced Metabolic Disorders
Insulin Therapy for Gestational Diabetes Mellitus Does Not Fully Protect Offspring From Diet-Induced Metabolic Disorders
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妊娠期糖尿病的胰岛素治疗并不能完全保护后代免受饮食引起的代谢紊乱
DOI：
10.2337/db18-1151
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发表时间：
2019-01
期刊：
影响因子：
7.7
通讯作者：
Huang He Feng
中科院分区：
文献类型：
--
作者：
Zhu Hong;Chen Bin;Cheng Yi;Zhou Yin;Yan Yi Shang;Luo Qiong;Jiang Ying;Sheng Jian Zhong;Ding Guo Lian;Huang He Feng
妊娠期糖尿病（GDM）与后代在以后生活中代谢紊乱的风险增加有关。尽管越来越多的证据表明，GDM治疗可以改善新生儿健康，但这种治疗是否能在后代成年后给他们带来长期的代谢益处尚不清楚。本研究利用妊娠后半期糖尿病小鼠模型模拟人类GDM，我们发现有效的胰岛素治疗GDM对正常饮食的后代葡萄糖耐受不良和肥胖具有显著的保护作用。然而，当高脂肪饮食挑战时，这种疗法无法保护后代，尤其是对雄性后代。来自雄性后代的胰岛的全基因组DNA甲基化分析发现，几个调节胰岛素分泌的基因中存在高甲基化区域，包括编码KATP或Ca2+通道的Abcc8、Cav1.2和Cav2.3，这与基因表达减少和胰岛素分泌受损有关。这一发现表明gdm诱导的代际葡萄糖耐受不良存在甲基化介导的表观遗传机制。它强调，即使有效的胰岛素治疗GDM也不足以完全保护成年后代免受饮食引起的代谢紊乱。
Gestational diabetes mellitus (GDM) is associated with an increased risk of metabolic disorders in offspring in later life. Although mounting evidence suggests that therapy for GDM could improve neonatal health, whether the therapy confers long-term metabolic benefits to offspring in their later adult lives is not known. Here, using a mouse model of diabetes in the latter half of pregnancy to mimic human GDM, we find that the efficient insulin therapy for GDM confers significant protection against glucose intolerance and obesity in offspring fed a normal chow diet. However, the therapy fails to protect offspring when challenged with a high-fat diet, especially for male offspring. Genome-wide DNA methylation profiling of pancreatic islets from male offspring identified hypermethylated regions in several genes that regulate insulin secretion, including Abcc8, Cav1.2, and Cav2.3 that encode KATP or Ca2+ channels, which are associated with reduced gene expression and impaired insulin secretion. This finding suggests a methylation-mediated epigenetic mechanism for GDM-induced intergenerational glucose intolerance. It highlights that even efficient insulin therapy for GDM is insufficient to fully protect adult offspring from diet-induced metabolic disorders.
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影响因子：
16.2
作者：
Gillman MW;Oakey H;Baghurst PA;Volkmer RE;Robinson JS;Crowther CA
通讯作者：
Crowther CA
影响因子：
4
作者：
Miao, Jie;Benomar, Yacir;Taouis, Mohammed
通讯作者：
Taouis, Mohammed
影响因子：
9.3
作者：
Tauscher S;Nakagawa H;Völker K;Werner F;Krebes L;Potapenko T;Doose S;Birkenfeld AL;Baba HA;Kuhn M
通讯作者：
Kuhn M
DOI：
10.12659/msm.909910
发表时间：
2018-04-21
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Wang Y;Wei RB;Yang Y;Su TY;Huang MJ;Li P;Chen XM
通讯作者：
Chen XM
影响因子：
21.3
作者：
Cigliola V;Ghila L;Thorel F;van Gurp L;Baronnier D;Oropeza D;Gupta S;Miyatsuka T;Kaneto H;Magnuson MA;Osipovich AB;Sander M;Wright CEV;Thomas MK;Furuyama K;Chera S;Herrera PL
通讯作者：
Herrera PL