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D Mangnall

Publications and source records attributed to D Mangnall.

12 recordsLinked to original sources
PubMed1992

Evidence that the insulin resistance of pregnancy may not involve a post-receptor defect in human adipocytes.

Insulin binding and the capacity of insulin to stimulate the conversion of glucose to carbon dioxide and lipid, and to activate the protein tyrosine kinase associated with the insulin receptor have been investigated in adipocytes isolated from pregnant and non-pregnant women. Insulin binding and the conversion of glucose to lipid were the same for both groups. However, conversion of glucose to CO2 was higher in the non-pregnant group due to an elevated basal activity, and the increase produced by insulin was similar in both groups. The tyrosine kinase activity of the isolated receptor preparations was higher in the pregnant group due to an increase in the basal non-insulin dependent activity, and the increase produced by insulin was similar in both groups. These findings show the in vitro insulin responsiveness of isolated adipocytes is similar for both groups, and suggests that the in vivo insulin resistance of late pregnancy, as far as adipose tissue is concerned, is not due to any inherent defect in insulin action at the receptor or post-receptor level. In vivo insulin resistance may result from an increased level of circulating insulin antagonists.

Adipose Tissue↗
PubMed1978

CTP-phosphatidic acid cytidyltransferase from Saccharomyces cerevisiae. Partial purification, characterization, and kinetic behavior.

CTP-phosphatidic acid cytidyltransferase catalyzes the formation of CDP-diglyceride from CTP and phosphatidic acid. The enzyme was solubilized from crude mitochondrial membrane by treatment with digitonin and was further purified by chromatography on DEAE-Sephadex, quaternary aminoethyl (QAE) Sephadex, and Sepharose 6B columns. At this stage the enzyme, enriched 550-fold over crude cell homogenate, still remains associated with phospholipid and has an estimated approximate molecular weight of 400,000 on the basis of gel filtration chromatography. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the 550-fold enriched enzyme yielded two major protein bands having molecular weights of 45,000 and 19,000. The enzyme exhibits an absolute dependence on Triton X-100, a sharp Mg2+ dependence with an optimum at 20 mM, and a pH optimum of 6.5 for activity. The product of the CTP-phosphatidic acid cytidyl-transferase reaction has been isolated and identified as CDP-diglyceride, both for the crude enzyme preparation as well as for the 550-fold enriched enzyme. CTP-phosphatidic acid cytidyltransferase is capable of catalyzing the reverse reaction in the presence of pyrophosphate, utilizing CDP-diglyceride as substrate. The product of the reverse reaction was identified as CTP. Kinetic analysis of the behavior of CTP-phosphatidic acid cytidyltransferase was performed at three different stages of its purification. Initial analysis of the data yielded biphasic behavior in double reciprocal plots with respect to both substrates. Hill plots of the data indicated the presence of negative cooperativity. A detailed analysis of the kinetic behavior was performed on the enzyme purified 550-fold. The data suggest a mechanism involving two distinct cycles of catalysis, responsive to homotropic modification, with different affinities for both substrates. Further analysis of the kinetic behavior in the presence of inhibitors (dCTP and PPi) yielded a reaction order for the entrance of substrates and departure of products from the reaction cycles. The high affinity site catalyzes the reaction via a double displacement mechanism and is the predominant form at low concentrations of substrates. At high concentrations of substrates the low affinity site starts contributing significantly to the reaction velocity with an ordered single displacement mechanism. In each case CTP is the first substrate to attach and PPi is the first product released.

Cytidine Diphosphate Diglycerides↗
PubMed1977

The analysis of decay curves.

1. The limitations inherent in the conventional treatment of glucose decay curves as first-order rate systems are described. 2. The conventionally derived K value is a rate constant and should not be confused with a rate. 3. First-order systems are described by this rate constant and the initial concentration of substance studied. They cannot be described by either factor alone. 4. Two parallel curves cannot both result from first-order systems. 5. If K is conventionally calculated for two parallel curves, then the value obtained for the upper curve must be smaller than the value for the lower.

Blood Glucose↗
PubMed1977

Changes in the proportions of plasma insulin, proinsulin and a higher-molecular-weight insulin during pre- and post-operative glucose-infusion tests.

1. Glucose-infusion tests were performed on patients admitted for elective upper abdominal surgery 1 day before and 1 day after operation. In addition to insulin and proinsulin, a third immunoreactive insulin species of mol. wt. 20 000--30 000 was detected in plasma from two patients. The heterogeneity of plasma immunoreactive insulin (IRI) and the need to consider the effects of all forms, including proinsulin and the high-molecular-weight species, is emphasized. 2. During preoperative glucose infusions there was an increase in the percentage of the total plasma IRI present as high-molecular-weight forms (i.e. proinsulin plus the species of mol. wt. 20 000--30 000) from 3.9% to 10.8%. On the first postoperative morning all patients showed an increase in the amounts of the heavier IRI types, which accounted for 13.9% of the total plasma IRI. 3. The changes in insulin and proinsulin are consistent with the release from the pancreas of an insulin/proinsulin mixture of constant proportions, and the longer circulating half-life of proinsulin. 4. Increases in the amounts of high-molecular-weight IRI species after surgery may have a partial role in the development of insulin resistance but are probably not a major determinant of the insulin-resistant state.

Adult↗
PubMed1977

Plasma insulin and surgery. I. Early changes due to operation in the insulin response to glucose.

The effects of elective abdominal operation on the disposal of a sustained intravenous glucose load and on the biphasic response of plasma insulin have been examined. During operation, low plasma insulin concentrations were observed despite the high plasma glucose values achieved. On the morning after operation, both phases of the insulin response to glucose were increased. This increase was seen even when subjects were compared at the same plasma glucose value. The response to tolbutamide was also greatly exaggerated. Pre- and postoperative glucose curves were approximately parallel, suggesting that glucose uptake was similar in both situations despite the presence of the postoperative hyperglycemia and hyperinsulinemia. This is at variance with previous reports based on conventional bolus dose intravenous tests which have suggested reduced postoperative glucose utilization. A new interpretation of the data is proposed.

Abdomen↗
PubMed1977

Plasma insulin and surgery. II. Later changes and the effect of intravenous carbohydrates.

Long-term hyperinsulinemia and improved glucose tolerance were produced postoperatively by intravenous feeding with glucose or sorbitol. Raised immuno-reactive insulin (IRI) values persisted eight hours after carbohydrate infusions although the basal plasma glucose concentrations had returned to control values. Plasma glucose curves were normal at this time but were associated with an increased IRI response. These findings suggest that insulin secretion is modified by glucose not only in the short term but also by a separate effect acting over many hours. The combination of starvation and low dose glucose infusion to simulate the hyperglycemia of operation also produced high IRI values but these were associated with a rapid fall in the plasma glucose curve. Starvation alone reduced basal values of plasma glucose and IRI, and the IRI response to glucose infusion was also reduced, despite the plasma glucose curve being at a higher level. It is suggested that the high values of IRI reported in the postoperative period are mediated by a long-term effect of the small but sustained rise in basal plasma glucose. This specific role of glucose in the long-term potentiation of insulin secretion make it the carbohydrate of choice for the intravenous feeding in postoperative patients.

Abdomen↗
PubMed1976

The relationship of plasma glucagon to the hyperglycaemia and hyperinsulinaemia of surgical operation.

In a controlled metabolic study of 42 patients undergoing abdominal surgery a significant increase in basal values of immunoreactive glucagon (IRG) was found 24 hours postoperatively. No correlation between the onset and duration of hyperglycaemia and the increase of IRG was observed. No increase in immunoreactive insulin (IRI) was seen during operation, but there was a rise 24 hours postoperatively. The infusion of arginine was accompanied by a rise in IRG both pre-and postoperatively, but despite the high values obtained there was no accompanying further increase in basal plasma glucose in the postoperative situation. The pre- and postoperative IRI responses were similar. Our evidence suggests that glucagon is not a primary mediator of the stress response, or of the hyperglycaemia of surgical operation in these patients.

Adult↗