研究人员发现一种因子，可以控制血糖新生之制造途径。这篇研究结果发表于4月号的Cell Metabolism中。
研究发现缺乏KLF15的小鼠，经过隔夜禁食后，会严重地缺乏血糖。KLF15是类KrÜpel转录因子家族中的一员。
研究人员经过追踪后发现，缺乏血糖是由于肝脏无法制造新的葡萄糖，这个过程又称为糖质新生。
糖质新生是一个复杂的过程。基本上，需要二个要素：制造血糖的积木和相关的酵素。之前的研究工作多半集中于酵素上。在这篇研究中，研究人员发现因为缺乏基质，而导致糖质新生的过程无法进行。
在禁食期间，食物的葡萄糖供应来源被切断，所以身体必需先分解肝糖，这是葡萄糖主要的贮存形式。但是，一旦储备的肝糖耗尽，身体必须仰赖肝脏中合成新的葡萄糖。葡萄糖新生仰赖于能否获得胺基酸基质分子。
研究员发现缺乏KLF15的小鼠在禁食隔夜后，发生严重的低血糖症。他们进一步发现了证据显示，缺乏KLF15导致小鼠无法获得一种名为丙酮酸盐的葡萄糖基质，因此导致小鼠禁食的低血糖症。
研究人员计划进一步探索KLF15调控葡萄糖生成的潜在机制，以及了解KLF15含量如何影响血糖制造，未来也有可能利用这项知识，帮助第二型糖尿病患者。
(资料来源 : Bio.com)
Cell Metabolism, Vol 5, 305-312, 04 April 2007
Short Article
Regulation of Gluconeogenesis by Krüppel-like Factor 15
Susan Gray,1,
Baiqiu Wang,3 Yvette Orihuela,1 Eun-Gyoung Hong,4,5 Sudeshna Fisch,1 Saptarsi Haldar,3 Gary W. Cline,5 Jason K. Kim,4,5 Odile D. Peroni,2 Barbara B. Kahn,2 and Mukesh K. Jain3,
1 Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
2 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
3 Case Cardiovascular Research Institute, Cardiovascular Division, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
4 Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
5 Department of Internal Medicine, Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, CT 06520, USA
Corresponding author
Susan Gray
sgray@rics.bwh.harvard.edu
Corresponding author
Mukesh K. Jain
mukesh.jain2@case.edu
Summary
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 (∼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.
英文全文链接：
http://www.cellmetabolism.org/content/article/fulltext?uid=PIIS1550413107000630
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