Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells.
Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells.
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DOI：
10.1038/ncomms13496
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发表时间：
2016-11-24
影响因子：
16.6
通讯作者：
Ashcroft FM
中科院分区：
文献类型：
--
作者：
Brereton MF;Rohm M;Shimomura K;Holland C;Tornovsky-Babeay S;Dadon D;Iberl M;Chibalina MV;Lee S;Glaser B;Dor Y;Rorsman P;Clark A;Ashcroft FM
胰腺β细胞的胰岛素分泌在所有形式的糖尿病中都受到损害。由此产生的高血糖对许多组织都有有害影响，包括β细胞。在这里，我们发现慢性高血糖损害了葡萄糖代谢，并改变了胰岛代谢基因的表达。在人类新生儿糖尿病的小鼠模型中，高血糖导致显著的糖原积聚，并增加β细胞的凋亡。磺脲类药物可迅速恢复血糖水平，消除糖原储备，增加自噬，恢复β细胞代谢。胰岛素治疗也有同样的效果，但动力学较慢。在高血糖的体外模型和2型糖尿病患者的胰岛中，也观察到了表达激活的葡糖激酶突变的小鼠的类似变化。β细胞代谢改变可能是糖尿病患者胰岛素分泌进行性损害和β细胞质量减少的原因。糖尿病的特征是长期的高血糖和胰岛的组织损伤。这里，Brereton等人。研究表明，慢性高糖水平导致β-细胞中糖原积聚，与自噬减少、代谢受损、胰岛素颗粒耗尽和细胞凋亡有关。
Insulin secretion from pancreatic β-cells is impaired in all forms of diabetes. The resultant hyperglycaemia has deleterious effects on many tissues, including β-cells. Here we show that chronic hyperglycaemia impairs glucose metabolism and alters expression of metabolic genes in pancreatic islets. In a mouse model of human neonatal diabetes, hyperglycaemia results in marked glycogen accumulation, and increased apoptosis in β-cells. Sulphonylurea therapy rapidly normalizes blood glucose levels, dissipates glycogen stores, increases autophagy and restores β-cell metabolism. Insulin therapy has the same effect but with slower kinetics. Similar changes are observed in mice expressing an activating glucokinase mutation, in in vitro models of hyperglycaemia, and in islets from type-2 diabetic patients. Altered β-cell metabolism may underlie both the progressive impairment of insulin secretion and reduced β-cell mass in diabetes. Diabetes is characterized by prolonged hyperglycaemia and tissue damage in pancreatic islets. Here, Brereton et al. show that chronic high glucose levels lead to glycogen accumulation in β-cells, associated with reduced autophagy, impaired metabolism, insulin granule depletion and apoptosis.
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影响因子：
8.2
作者：
Babiker T;Vedovato N;Patel K;Thomas N;Finn R;Männikkö R;Chakera AJ;Flanagan SE;Shepherd MH;Ellard S;Ashcroft FM;Hattersley AT
通讯作者：
Hattersley AT
影响因子：
11.1
作者：
Duran, Jordi;Florencia Tevy, Maria;Garcia-Rocha, Mar;Calbo, Joaquim;Milan, Marco;Guinovart, Joan J.
通讯作者：
Guinovart, Joan J.
影响因子：
15.9
作者：
Kim, Jinyoung;Cheon, Hwanju;Lee, Myung-Shik
通讯作者：
Lee, Myung-Shik
影响因子：
29
作者：
Ebato, Chie;Uchida, Toyoyoshi;Watada, Hirotaka
通讯作者：
Watada, Hirotaka
慢性高血糖引发糖尿病动物模型胰腺β细胞分化丧失
影响因子：
4.8
作者：
Jonas, JC;Sharma, A;Weir, GC
通讯作者：
Weir, GC