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Publication
Regulation of gluconeogenesis by Krüppel-like factor 15.
Authors Gray S, Wang B, Orihuela Y, Hong EG, Fisch S, Haldar S, Cline GW, Kim JK, Peroni
OD, Kahn BB, Jain MK
Submitted By Mukesh Jain on 11/6/2007
Status Published
Journal Cell Metabolism
Year 2007
Date Published
Volume : Pages 5 : 305 - 312
PubMed Reference 17403374
Abstract In the postabsorptive state, certain tissues, including the brain, require
glucose as the sole source of energy. After an overnight fast, hepatic glycogen
stores are depleted, and gluconeogenesis becomes essential for preventing
life-threatening hypoglycemia. Mice with a targeted deletion of KLF15, a member
of the Krüppel-like family of transcription factors, display severe hypoglycemia
after an overnight (18 hr) fast. We provide evidence that defective amino acid
catabolism promotes the development of fasting hypoglycemia in KLF15-/- mice by
limiting gluconeogenic substrate availability. KLF15-/- liver and skeletal
muscle show markedly reduced mRNA expression of amino acid-degrading enzymes.
Furthermore, the enzymatic activity of alanine aminotransferase (ALT), which
converts the critical gluconeogenic amino acid alanine into pyruvate, is
decreased (approximately 50%) in KLF15-/- hepatocytes. Consistent with this
observation, intraperitoneal injection of pyruvate, but not alanine, rescues
fasting hypoglycemia in KLF15-/- mice. We conclude that KLF15 plays an important
role in the regulation of gluconeogenesis.




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