CONTROL ENZYMES OF GLUCONEOGENESIS

高血糖素在碳水化合物调节中作用方式的阐明 新陈代谢与更好地理解糖尿病的病因有直接关系。 糖尿病状态下的高血糖。胰升糖素的作用部位之一发生在 在果糖6-磷酸-1，6-二磷酸果糖相互转化步骤中， 但胰高血糖素作用于这一步骤的分子机制(S)仍有待进一步研究。 已经成立了。为了深入了解这些机制， 这项研究上述代谢步骤所涉及的酶的建议，即 磷酸果糖激酶和果糖1，6-二磷酸酶。在这一一般上下文中， 这项研究将包括：(A)肝磷酸果糖激酶的研究 C57BL/KSJ正常和糖尿病小鼠；(B)体外蛋白降解研究 C57BL/KSJ正常人和糖尿病患者果糖1，6-二磷酸酶活性的研究 小鼠；(C)氨基酸残基和/或区域的识别研究 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(C57BL/KSJ-db)是 以普遍存在的高血糖素血症为特征的，并伴有缺乏有效的 循环胰岛素，被认为是人类成熟的模式系统 发病的糖尿病。

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.