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Merck
  • Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids.

Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids.

Cell reports (2022-04-28)
Michael R Martino, Manuel Gutiérrez-Aguilar, Nicole K H Yiew, Andrew J Lutkewitte, Jason M Singer, Kyle S McCommis, Daniel Ferguson, Kim H H Liss, Jun Yoshino, M Katie Renkemeyer, Gordon I Smith, Kevin Cho, Justin A Fletcher, Samuel Klein, Gary J Patti, Shawn C Burgess, Brian N Finck
摘要

Hepatic gluconeogenesis from amino acids contributes significantly to diabetic hyperglycemia, but the molecular mechanisms involved are incompletely understood. Alanine transaminases (ALT1 and ALT2) catalyze the interconversion of alanine and pyruvate, which is required for gluconeogenesis from alanine. We find that ALT2 is overexpressed in the liver of diet-induced obese and db/db mice and that the expression of the gene encoding ALT2 (GPT2) is downregulated following bariatric surgery in people with obesity. The increased hepatic expression of Gpt2 in db/db liver is mediated by activating transcription factor 4, an endoplasmic reticulum stress-activated transcription factor. Hepatocyte-specific knockout of Gpt2 attenuates incorporation of 13C-alanine into newly synthesized glucose by hepatocytes. In vivo Gpt2 knockdown or knockout in liver has no effect on glucose concentrations in lean mice, but Gpt2 suppression alleviates hyperglycemia in db/db mice. These data suggest that ALT2 plays a significant role in hepatic gluconeogenesis from amino acids in diabetes.

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Sigma-Aldrich
胶原酶 来源于溶组织梭菌, suitable for release of physiologically active rat hepatocytes, Type IV, 0.5-5.0 FALGPA units/mg solid, ≥125 CDU/mg solid
Sigma-Aldrich
葡萄糖 (GO) 检测试剂盒, sufficient for 20 assays
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衣霉素 来源于链霉菌
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UK-5099, ≥98% (HPLC)
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抗-GPT2 兔抗, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution