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Biomedical subjects

W A Muller

Publications and source records attributed to W A Muller.

At least 73 records · Page 4Linked to original sources
PubMed1979

[Fractional distribution of anti-glucagon immunoreactivity (GIR) and amino acid concentration in the plasma in duodenopancreatectomized patients; preliminary report].

Glucagon immunoreactivity (IRG) was measured in plasma of 8 duodenopancreatectomized patients with antiserum 30-K. Arginine infusions failed to raise plasma IRG, whereas in control subjects IRG rose 3-fold. Column chromatography revealed that the basal IRG measured in these plasmas was not due to glucagon (molecular weight 3485) but to other plasma factors, mainly of high molecular weight. This suggests that diabetes mellitus does not require the presence of glucagon to produce the clinical picture, as suggested by other authors. Plasma levels of the amino acids alanine, serine, ornithine, and arginine were significantly (p less than 0.05) elevated, the former two being gluconeogenic substrates and the latter two constituents of the urea cycle. This amino acid abnormality may be a consequence of glucagon deficiency.

Amino Acids↗
PubMed1979

Plasma glucagon in diabetes of haemochromatosis: too low or too high?

Glucagon secretion before and during arginine infusions was tested in 11 patients with diabetes associated with haemochromatosis. The results were compared with those obtained in six normal subjects and five patients with haemochromatosis but normal glucose tolerance. The patients with haemochromatosis, regardless of glucose tolerance, exhibited higer level of plasma immunoreactivity for glucagon (antiserum 30-K) suggesting hyperglucagonaemia. However, additional analysis revealed that a considerable amount of this glucagon immunoreactivity was due to cross-reacting material of high molecular weight, the levels of which were significantly higher in patients with idiopathic haemochromatosis. When this was deducted from the total immunoreactivity measured, the resulting values for true glucagon concentrations were similar to those of normal subjects. The data suggest that (1) patients with idiopathic haemochromatosis, whether or not associated with diabetes, exhibit plasma glucagon levels comparable with those of normal subjects; (2) the plasma of the same patients contains significantly more high-molecular-weight substances reacting with glucagon antiserum 30-K than is present in plasma of normal subjects; and (3) 'hyperglucagonaemia' may be erroneously suggested when glucagon is measured with certain antisera reputed to be specific for glucagon.

Arginine↗
PubMed1979

Identical biological effects of pancreatic glucagon and a purified moiety of canine gastric immunoreactive glucagon.

Because in the dog, the gastric fundus contains the largest amount of glucagon immunoreactivity (IRG), the IRG of mucosal scrapes of 105 canine stomachs was extracted by acid-ethanol and then precipitated by ether-ethanol. The IRG recovered was measured by antisera 30K, specific for glucagon and K-4023, which cross-reacts with glucagon-like immunoreactivity. Extracts of mucosa of stomach fundus were further purified by gel filtration on Bio-Gel P-30 in 3M acetic acid. One pooled fraction corresponding to marker pancreatic glucagon in its elution volume was then gel-filtered on Bio-Gel P-30 in 0.05 M NH(4)HCO(3) and yielded one IRG peak, which, however, showed three immunoreactive components on polyacrylamide disc gel electrophoresis in urea. In addition, antiserum K-4023 reacted more strongly with that peak than antiserum 30K indicating the presence of glucagon-like immunoreactivity in this fraction. Subsequent ion-exchange column chromatography on DEAE-Sephadex A-25 and then CM-Bio-Gel A allowed purification to a single protein band on disc gel electrophoresis reacting equally to both antisera 30K and K-4023. 1.5 mug of purified gastric glucagon was obtained and its biological effects were compared to those of pancreatic glucagon in isolated rat hepatocytes. When immuno-equivalent amounts (300-2,500 pg/ml) of either type of glucagon were used, the same biological responses with respect to glycogenolysis and gluconeogenesis as well as urea, lactate, and pyruvate production were observed. Liver cyclic AMP was also raised to the same extent by either one of these hormones. We conclude that this moiety of gastric IRG is apparently identical to pancreatic glucagon because (a) their molecular weights, elution properties in ion exchange chromatography, and their electrophoretic mobility are indistinguishable and (b) both hormones elicited identical biological effects in isolated rat hepatocytes.

Animals↗
PubMed1979

Glucagon immunoreactivities and amino acid profile in plasma of duodenopancreatectomized patients.

Glucogon immunoreactivity (IRG) was measured in plasma of duodenopancreatectomized subjects with a nonspecific (K-4023) and a specific (30-K) glucagon antiserum. After an overnight fast, plasma IRG (K-4023) was significantly (P < 0.05) higher in the subjects without pancreas, averaging 782+/-79 (SEM) pgeq/ml, than in the controls (482+/-80 pgeq/ml). IRG (30-K) of 162+/-68 pg/ml did not change during an infusion of arginine (450 mg/kg per 40 min). Insulin deprivation during 3 d in one patient did not restore the IRG response to arginine as reported in depancreatized dogs.Bio-Gel P-30 column chromatography revealed that virtually all IRG (30-K) measured in whole plasma was of different molecular weight than glucagon, and primarily of a mol wt >/= 40,000. Intravenous arginine did not significantly alter the chromatographic pattern of these plasmas. Thus, as postulated by others, duodeno-pancreatectomized humans have virtually no circulating 3,500-dalton glucagon. Hence, the presence of 3,500-dalton glucagon in plasma is not a condition for the diabetic state. It might, nevertheless, when present in normal or excessive amounts, worsen the metabolic state of diabetic patients. Among 14 amino acids measured in plasma of these patients, the concentrations of alanine, serine, ornithine, and arginine were significantly (P < 0.05) elevated to approximately twice that of normal: alanine and serine are both substrates for gluconeogenesis, whereas ornithine and arginine are involved in the formation of urea, the second product of hepatic gluconeogenesis. As the concentrations of branched chain amino acids were not grossly altered, it is hypothesized that this amino acid pattern is a consequence of glucagon deficiency rather than secondary to the diabetic state of these patients.

Adult↗
PubMed1978

Extrapancreatic glucagon and glucagonlike immunoreactivity in depancreatized dogs. A quantitative assessment of secretion rates and anatomical delineation of sources.

The anatomical sites and the rates of extrapancreatic secretion of glucagon and of glucagon-like immunoreactivity (GLI) were assessed in dogs 2 h after pancreatectomy by catheterization of the gastrosplenic and mesenteric veins. Glucagon release from the gastrosplenic area approximated one-fourth that of a normal pancreas and rose from 0.25 to 1.0 ng/kg per min during arginine stimulation. Intestinal glucagon secretion was small and did not respond to arginine, suggesting that the stomach is the only important extrapancreatic source of glucagon. Glucagon concentrations attained by gastrosplenic secretion were in close proportion to those obtained during the administration of exogenous glucagon, indicating similar clearance rates of extrapancreatic and pancreatic glucagon, approximating 10 ml/kg per min.GLI secretion (0.3 ng eq/kg per min) was limited to the intestinal area and was transiently stimulated by arginine and exogenous glucagon. Base-line GLI clearance approximated 1 ml/kg per min. No insulin secretion could be detected. Gastrointestinal glucose uptake rose from 0.56 to 2.2 mg/kg per min after glucagon administration suggesting that as much as 10% of total glucose production can be taken up by the gastrointestinal tract. In two dogs both the stomach and pancreas were removed. Intestinal glucagon release remained small and did not increase during arginine administration. By contrast, GLI release was stimulated by both arginine and exogenous glucagon.

Animals↗
PubMed1977

[Study of glucagon secretion in patients with hemochromatosis].

Diabetes in idiopathic hemochromatosis has been considered to be secondary to islet cell damage resulting from the iron deposits. Plasma glucagon was measured by immunoassay using the pancreas specific 30-K antiserum, and was found to be normal or slightly elevated during arginine-infusion tests in patients exhibiting both hemochromatosis and pathological glucose tolerance. This suggests that diabetes in hemochromatosis is not due to a lesion resulting from the iron deposits. The two affections appear to be merely associated and are possibly genetically linked.

Diabetes Mellitus↗
PubMed1977

Effects of exogenous glucagon and epinephrine in physiological amounts on the blood levels of free fatty acids and glycerol in dogs.

Exogenous glucagon or epinephrine were infused into normal overnight fasted dogs to raise circulating hormone levels to concentrations within the physiologic range. Plasma levels of glycerol and free fatty acids remained unchanged during the glucagon infusion, but rose significantly during the administration of epinephrine. Plasma insulin in the systemic circulation remained unchanged during the glucagon infusion and increased slightly during the infusion of thecatecholamine. The data suggest that in normal dogs glucagon in physiological amounts has no lipolytic effect. The importance of the sympathetic nervous system in regulating lipolysis in normal mammals is stressed.

Animals↗
PubMed1976

Subcutaneous, isogeneic transplantation of duct-ligated pancreas in streptozotocin diabetic mice: relationships between recovery and hormone contents in transplants or host pancreas.

Recovery from diabetes was observed in streptozotocin-treated mice that received subcutaneous, isogeneic transplants of duct-ligated pancreas. Transplants excised from recovered hosts contained both immunoreactive insulin (IRI) and glucagon (IRG), indicating that both A and B cells capable of hormone storage were present. The IRI content in transplants, although only one sixth of that transplanted 6 wk earlier, was still 21/2 times greater than that in the host pancreas and was inversely related to the plasma glucose of the recipient during and after recovery. The IRI content in the transplant added to that in the host pancreas totaled 13% of the IRI found in the normal mouse pancreas, which sufficed for over-all recovery from diabetes but was insufficient to provide normal glucose tolerance and insulin response to a major glucose challenge. The abnormally high content of glucagon noted in the pancreas of hyperglycemic, sham transplanted mice was reduced by one-half in the pancreas of those transplanted mice returning to normal plasma glucose and insulin. Thus, the insulin content of the transplant was important to the recovery of isografted mice, but in addition, and perhaps as a consequence of recovery, there was a slight increase in the insulin storage capacity of the host pancreas and a marked reduction of glucagon compared to the content of these hormones in the pancreas of hyperglycemic, sham transplanted mice.

Animals↗
PubMed1976

Phosphorylation reactions in islets of Langerhans.

The possible significance of phosphorylation reaction in islets of Langerhans in relation to the secretion of insulin is discussed. The secretagogues, glucose and its metabolites, cAMP and Ca++ and their influences on protein-kinase activity are given particular attention. The data obtained by the authors, as well as by other groups, are in agreement that cAMP is a potent stimulator of protein kinase activity. Glucose and its metabolites influenced protein kinase activity in one instance. Ca++ in supraphysiological amounts inhibited protein phosphorylation. The links between phosphorylation reactions and insulin secretion are, at the present time, conjectural.

Animals↗
PubMed1975

Retardation time measurementson replicating bacillus subtilis chromosomes: effect of EDTA concentration.

We have found that high concentrations of EDTA (greater than 0.024 M) are necessary to produce large, constant numbers of intact replicating Bacillus subtilis chromosomes in lysates of log phase cells. The retardation time of replicating chromosomes in log phase cell lysates is about double that for chromosomes in stationary phase cell lysates, thus making measurement of retardation time a sensitive way to detect and study replicating chromosomes. A theory is developed to predict retardation times for many possible models of DNA replication. The retardation time data on log phase cells is sufficient to eliminate many replication models, but many possibilities remain.

Bacillus subtilis↗