Martino 2022 Cell Rep

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Publications in the MiPMap
Martino MR, GutiΓ©rrez-Aguilar M, Yiew NKH, Lutkewitte AJ, Singer JM, McCommis KS, Ferguson D, Liss KHH, Yoshino J, Renkemeyer MK, Smith GI, Cho K, Fletcher JA, Klein S, Patti GJ, Burgess SC, Finck BN (2022) Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids.

Β» Cell Rep 39:110733. PMID: 35476997 Open Access

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

Abstract: 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. β€’ Keywords: ATF4, CP, Metabolism, GPT2, Amino acids, Gluconeogenesis, Liver β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: US MO St Louis McCommis KS, US MO St Louis Finck B

Labels: MiParea: Genetic knockout;overexpression  Pathology: Diabetes 

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