Nutrient sensing in pancreatic islets: lessons from congenital hyperinsulinism and monogenic diabetes.
Nutrient sensing in pancreatic islets: lessons from congenital hyperinsulinism and monogenic diabetes.
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DOI：
10.1111/nyas.13448
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发表时间：
2018-01
影响因子：
5.2
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Lu M;Li C
胰腺β细胞在禁食和进食周期期间感知营养物质的变化，并相应地释放胰岛素以维持葡萄糖稳态。由基因突变引起的异常β细胞营养感测导致低血糖或糖尿病。葡萄糖激酶（GCK）在β细胞葡萄糖传感中起关键作用。作为先天性高胰岛素血症（CHI）的一种形式，GCK的激活突变导致葡萄糖刺激的胰岛素分泌（GSIS）阈值降低和低血糖。相反，GCK的失活突变导致糖尿病，包括轻度形式（MODY2）和重度形式（永久性新生儿糖尿病，PNDM）。参与胰岛素分泌调节的β细胞离子通道的突变也改变葡萄糖感知。ATP依赖性钾（KATP）通道的激活或失活突变导致严重但完全相反的临床表型，包括PNDM和CHI。其他离子通道的突变，包括电压门控钾通道（Kv7.1）和电压门控钙通道，也会导致异常的葡萄糖感知和CHI。此外，在某些形式的CHI中，氨基酸可以以葡萄糖非依赖性方式刺激胰岛素分泌，包括谷氨酸脱氢酶的激活突变、HDAH缺陷和KATP通道的失活突变。这些遗传缺陷为更好地理解β细胞燃料传感机制的复杂性质提供了见解。
Pancreatic beta cells sense changes in nutrients during the cycles of fasting and feeding and release insulin accordingly to maintain glucose homeostasis. Abnormal beta cell nutrient sensing resulting from gene mutations leads to hypoglycemia or diabetes. Glucokinase (GCK) plays a key role in beta cell glucose sensing. As one form of congenital hyperinsulinism (CHI), activating mutations of GCK result in a decreased threshold for glucose-stimulated insulin secretion (GSIS) and hypoglycemia. In contrast, inactivating mutations of GCK result in diabetes, including a mild form (MODY2) and a severe form (permanent neonatal diabetes mellitus, PNDM). Mutations of beta cell ion channels involved in insulin secretion regulation also alter glucose sensing. Activating or inactivating mutations of ATP-dependent potassium (KATP) channels results in severe but completely opposite clinical phenotypes, including PNDM and CHI. Mutations of the other ion channels, including voltage-gated potassium channels (Kv7.1) and voltage-gated calcium channels, also lead to abnormal glucose sensing and CHI. Furthermore, amino acids can stimulate insulin secretion in a glucose-independent manner in some forms of CHI, including activating mutations of glutamate dehydrogenase, HDAH deficiency, and inactivating mutations of KATP channels. These genetic defects have provided insight into a better understanding of the complicated nature of beta cell fuel-sensing mechanisms.
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影响因子：
4.1
作者：
Casimir, Marina;Rubi, Blanca;Maechler, Pierre
通讯作者：
Maechler, Pierre
影响因子：
4.8
作者：
De Leon, Diva D.;Li, Changhong;Stoffers, Doris A.
通讯作者：
Stoffers, Doris A.
影响因子：
7.7
作者：
Cuesta-Muñoz, AL;Huopio, H;Laakso, M
通讯作者：
Laakso, M
DOI：
10.1042/cs20090126
发表时间：
2009-09-01
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Bender K;Maechler P;McClenaghan NH;Flatt PR;Newsholme P
通讯作者：
Newsholme P
影响因子：
15.9
作者：
Dhawan, Sangeeta;Tschen, Shuen-Ing;Bhushan, Anil
通讯作者：
Bhushan, Anil