CONTROL ENZYMES OF GLUCONEOGENESIS

胰高血糖素调节碳水化合物的作用方式 代谢直接关系到更好地理解的原因， 糖尿病状态下的高血糖。 胰高血糖素的作用部位之一是 在果糖6-磷酸-果糖1，6-二磷酸相互转化步骤中， 但是胰高血糖素作用于该步骤的分子机制仍有待进一步研究 确立了习 为了深入了解这些机制， 这项研究涉及上述代谢步骤的酶的建议，即 磷酸果糖激酶和果糖1，6-二磷酸酶。 在这一大背景下， 这项研究将包括：（a）研究肝脏磷酸果糖激酶， C57 BL/KsJ正常和糖尿病小鼠;（B）C57 BL/KsJ正常和糖尿病小鼠的体外蛋白水解研究 来自C57 BL/KsJ正常和糖尿病患者的蛋白酶的果糖1，6-二磷酸酶 （c）鉴定氨基酸残基和/或区域的研究 参与果糖1，6-二磷酸酶的功能和调节。 用于这些研究的遗传性糖尿病小鼠（C57 BL/KsJ-db）是 其特征在于普遍存在高胰高血糖素血症，伴有缺乏有效的 循环胰岛素，并被认为是人类成熟的模型系统 初发糖尿病

The elucidation of the mode of glucagon action in regulation of carbohydrate metabolism is directly related to a better understanding of the causes of hyperglycemia in the diabetic state. One of the sites of glucagon action occurs at the fructose 6-phosphate - fructose 1,6-bisphosphate interconversion step, but the molecular mechanism(s) by which glucagon acts on this step remains to be established. To gain an insight into these mechanisms, it is the objective of this proposal to study the enzymes involved in the above metabolic step, namely phosphofructokinase and fructose 1,6-bisphosphatase. In this general context, this research will cover: (a) Studies on liver phosphofructokinase from C57BL/KsJ normal and diabetic mice; (b) Studies of in vitro proteolysis of fructose 1,6-bisphosphatase by proteases from C57BL/KsJ normal and diabetic mice; (c) Studies on the identification of amino acid residues and/or regions involved in the function and regulation of fructose 1,6-bisphosphatase. The genetically diabetic mouse to be used in these studies (C57BL/KsJ-db) is characterized by prevailing hyperglucagonemia accompanied by a lack of effective circulating insulin, and is considered to be a model system of human maturity onset diabetes.