James Ashmore

The Role of Hepatic Glucose-6-phosphatase in the Regulation of Carbohydrate Metabolism

Publisher Summary Many attempts have been made to assign to enzymes the role of biochemical regulators as well as the function of catalysts. For example, changes in the rate of glycogenolysis have been associated with changes in phosphorylase activity. Although the mechanism of hormone action is not completely understood, many instances have been recorded of change in enzymatic activity under various endocrine conditions. Congenital diseases involving abnormal metabolism have been attributed to an ever-increasing number of enzyme deficiencies. Glucose-6-phosphatase, an enzyme involved in hepatic glucose production, has been studied from these several points of view. Recent studies have indicated that this enzyme may have a role in the regulation of hepatic glucose production. The activity of hepatic glucose-6-phosphatase is altered by fasting and alloxan diabetes, is virtually absent in glycogen storage disease and hepatoma, and is readily changed by endocrine manipulation. Such studies have been summarized in this chapter for review and evaluation. An extension of these observations has revealed a striking correlation between the activity of this enzyme and endocrine regulation of carbohydrate metabolism.

Hexokinase, glucose-6-phosphatase and phosphorylase levels in hereditarily obese-hyperglycemic mice.

Abstract The skeletal muscle and kidney hexokinase activities of the obesehyperglycemic mice and their nonobese controls were of the same magnitude. The liver glucose-6-phosphatase activities per gram of liver were similar in the obese-hyperglycemic mice and their controls. The total liver glucose-6-phosphatase activity was significantly greater in the obesehyperglycemic mice than in their nonobese siblings. The diabetes of these obese mice thus differs biochemically from alloxan diabetes in which there are decreased hexokinase and increased glucose-6-phosphatase activities. The liver phosphorylase activity per unit weight of liver in the obesehyperglycemic mice was significantly greater (P

Studies on the Disposition of Blood Glucose: A Comparison of Insulin and Orinase

Preparation of animals. Mongrel dogs weighing from 17 to 21 kg. were anesthetized with intravenous Nembutal, 30 mg./kilo. Respiration was maintained during the intrathoracic portion of the procedure using a positive pressure pump and endotracheal tube. Aseptic technic was maintained throughout the surgical procedure. The operation has been described in some detail since it has proved a useful and successful technic in studying hepatic physiology. The upper abdomen was entered through a short midline incision, the spleen removed, and the splenic artery and vein isolated. Two cannulae (consisting of a tip of 205 gauge polyethylene tubing 12 cm. long joined to a 60 cm. length of nonkinking Genflex plastic tubing by a larger gauge polyethylene cuff) were threaded into the splenic artery and vein and guided respectively into the aorta and portal vein. The cannulae were sutured in place to the cut ends of the splenic vessels through a heat-flared polyethylene cuff. In this way the less reactive polyethylene tip lay within the vessel. The cannulae were filled with dilute heparin, closed at the distal ends with variously colored aluminum plugs, and passed subcutaneously over the right rib margin and beneath the skin of the right lateral

Studies on the disposition of isotopic glucose in vivo and in vitro under the influence of sulfonylureas.

Insulin and sulfonylureas have the common property of being able to reduce the concentration of blood glucose in normal animals. Whether or not this fall in blood glucose is elicited by Lhe same mechanism is the current subject of discussion. As an approach to this problem, we have compared the effects of insulin and tolbutamidek on various aspects of glucose disposition in unanesthetized dogs and rats and in isolated tissue preparations.

Regulation of Carbohydrate Metabolism in Isolated Tissues

Publisher Summary The presence of an important regulatory mechanism for the normal functioning of carbohydrate metabolism has been apparent since Willis discovery that the urine of patients affected by the strange and rapidly wasting disease, already known as diabetes, was sweet to the taste. Further prima facie evidence for the existence of such a regulation resulted from the observation of stable blood glucose concentrations in the face of pronounced alterations in its rate of accretion and in its rate of depletion. A complex regulatory system had to be postulated in order to insure adequate coordination between mainly glucose-producing and mainly glucose-utilizing tissues. Though nervous signals have been established, chemical signals appear to be chiefly responsible for this regulation of carbohydrate metabolism. This chapter is restricted to the discussion on the influence of hormones, of variations in the available substrates (such as changes in diet or fasting), and of changes in the intracellular and extracellular environment, such as those produced by variations in the absolute or relative concentration of ions.

Effect of Bile Acids on Activity of GIucose-6-Phosphatase.

Summary (1) Bile acids have been found to influence, in vitro, the activity of rat liver glucose-6-phosphatase, concentrations of 5 × 10-4 M inactivating and 1 × 10-3 M activating the enzyme. (2) Glucose-6-phosphatase from both normal and diabetic rats responds similarly. The increased glucose-6-phospha-tase activity found in liver of alloxan diabetic rats therefore does not appear to be due to any such activation mechanism, but rather due to an actual increase in the amount of enzyme present.

Intracellular ionic environment and enzyme activities: Carbohydrate metabolism in liver☆

Abstract 1. 1. The role of the maintenance of the intracellular ionic environment in certain metabolic reactions in liver has been noted. 2. 2. An examination has been made of the extent to which alternative reactions open to glucose 6-phosphate are influenced by sodium and potassium. 3. 3. Experimental evidence is presented which indicates that liver phosphorylase activity and glycogenolysis are greater in a high sodium than in a high potassium medium.