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SUMMARY
Human foetal adrenal slices were incubated with [4-14C]pregnenolone (20 foetuses) and [4-14C]dehydroepiandrosterone (18 foetuses). Product 4-ene-3-oxosteroids were isolated as a group and measured in toto by a double isotope dilution procedure. Production of compounds of the 4-ene-3-oxosteroid fraction was estimated over several time-intervals and relative to the protein content of the incubated tissue.
No conversion of [4-14C]pregnenolone by foetal adrenal tissue to 4-ene-3-oxosteroids was detectable although metabolism of the substrate to other compounds was indicated. Conversion of [4-14C]dehydroepiandrosterone to 4-ene-3-oxosteroids, principally androstenedione, occurred in incubations of tissue from 7 of the 10 male foetuses studied with this substrate, and from 2 of undetermined sex, but not from 6 female foetuses so studied. Testosterone formation from [4-14C]dehydroepiandrosterone was not detectable. There was no apparent variation in 4-ene-3-oxosteroid formation relative to foetal age in the range investigated (approximately 6–20 foetal weeks).
These results are interpreted, in the light of previous studies, as giving credence to the concept of substrate specificity in human foetal adrenal 4-ene-3-oxosteroid formation. The evidence that foetal adrenal androstenedione formation may be sex-dependent is considered, and the implications discussed.
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Search for other papers by K. W. TAYLOR in
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SUMMARY
The secretory response of rat islets of Langerhans was examined during pregnancy and compared with insulin release in normal rat islets. The threshold for a secretory response to glucose was lowered for islets from pregnant rats by comparison with non-pregnant controls. In addition, such islets showed a greatly increased sensitivity to glucose concentrations over the range 3·5–20 mmol/1. Significantly lower fasting blood glucose levels were found in pregnant rats in vivo, compared with controls.
Insulin secretagogues other than glucose were tested for their effects on islets during pregnancy. Despite the high baseline of insulin secretion in response to glucose in pregnancy, there was an additional increased secretory response to arginine and theophylline. In contrast to their response to glucose, pregnant rat islets did not display an increased sensitivity to leucine. Glucagon, while it increased the insulin response of normal islets, had no significant effect on increasing the insulin response from pregnant rat islets suggesting that adenyl cyclase activity is already highly stimulated in pregnancy.
In addition, the insulin, DNA and protein content of islets during pregnancy were increased significantly above normal values.
The results suggested that rat islets are not only larger in pregnancy, but that they possess a more sensitive mechanism for detecting and responding to glucose and other secretagogues.
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Search for other papers by D. G. PARRY in
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The effects of sugars such as glucose or mannose in promoting release of insulin from beta cells appears to be paralleled by a simultaneous increase in insulin synthesis (Parry & Taylor, 1966). It has been argued that such effects are physiologically important in that they prevent an undue depletion of β cell reserves of insulin under conditions of maximal stimulation by sugars. Whether the secretion of insulin induced by drugs like tolbutamide is also accompanied by a simultaneous enhancement of insulin synthesis is not known. Work on animals in vivo suggests that tolbutamide may very rapidly deplete the pancreas of insulin (Root, 1957). The experiments to be reported suggest that tolbutamide is without effects on the incorporation of amino acids into insulin.
Effects of tolbutamide were tested on incorporation into rabbit insulin in vitro, by methods described in detail elsewhere (Taylor, Gardner, Parry & Jones, 1965; Mallory, Smith & Taylor,
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Search for other papers by K. W. TAYLOR in
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SUMMARY
The effects of diet on the altered insulin secretory responses of islets of Langerhans of pregnant rats have been investigated. The daily food intake of pregnant rats was found to exceed that of control non-pregnant rats by 20% on average. Depriving pregnant rats of this additional food resulted in an alteration in the pattern of insulin secretion seen in pregnancy, such that the sensitivity to stimulation by low glucose concentrations was abolished. The contribution made by different components of the diet to the secretory response in pregnancy was investigated. When additional carbohydrate, though not protein, was fed to pregnant rats on a restricted food intake, the sensitivity of the islets to glucose stimulation was restored. It was concluded that the quantity and in particular the carbohydrate content of food eaten by pregnant rats exerts an important influence on the changes in insulin secretion in pregnancy.
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Search for other papers by K. W. TAYLOR in
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Methods for the immunoassay of blood insulin by double antibody techniques have recently been devised by Hales & Randle (1963) and Morgan & Lazarow (1963). The first of these methods has proved extremely satisfactory, and has in general given values for serum insulin which are in close agreement with those obtained by most other immunoassay procedures. However, using method C of Hales & Randle on sera from twenty-three normal, non-obese subjects, with no family history of diabetes mellitus, excessively high values for serum insulin were found repeatedly in three of the subjects, both in the fasting state and after glucose. It seemed possible that the reason for these high values might lie in the presence in their serum of a factor, similar to that described by Morgan, Sorensen & Lazarow (1964) in rat plasma, which may inhibit the precipitation of the insulin-antibody complex. It has been suggested by Morgan et
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Search for other papers by K. W. TAYLOR in
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SUMMARY
The origin of the pronounced hypoglycaemic phase during the onset of alloxan diabetes in the rabbit has been investigated.
Blood sugar and serum insulin levels were recorded 6, 12 and 24 hr. after alloxan administration and were related to changes in the insulin content of the pancreas and to the rate of insulin release from pancreas slices in vitro at similar time intervals. During the phase of hypoglycaemia, serum insulin levels were elevated, and insulin release from the pancreas slices was markedly increased, but a decrease in the quantity of insulin extractable from the pancreas occurred during the same 6 hr. period.
These results indicate that the hypoglycaemia may result from an unregulated release of preformed insulin from the β cells, during their destruction after the administration of alloxan.
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The chemical nature of insulin in islet cell tumours of the pancreas has recently been the subject of some discussion. Thus it has been suggested that such insulin does not react with fluorescent antibody (Lacey & Williamson, 1960). Nevertheless, the A-chain derived from insulin which had been obtained from another such tumour has been reported to have an amino acid composition identical with the A-chain derived from human pancreatic insulin (L. F. Smith, personal communication). There is clearly a need for further investigation of the characteristics of insulin present in tumours of this kind. Some of the chemical and immunological properties of the insulin extracted from another such tumour are given below.
The patient, a 13-year-old girl, was transferred from a psychiatric hospital after attacks of altered consciousness had been observed to be associated with low blood sugar levels. Six hours after the ingestion of 50g. glucose, the blood sugar
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Search for other papers by W. TAYLOR in
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SUMMARY
The effects of testosterone propionate (TP) and of 17α-ethyl-19 nor-testosterone (ENT) on the submandibular glands, levator ani muscles and seminal vesicles of castrated mice have been compared. ENT restores submandibular weight and histology about as well as TP but has less effect on the levator ani muscle and much less effect on the seminal vesicles. Both steroids can act directly on the submandibular gland. It is suggested that the effect on the gland may be an indication of the 'anabolic' rather than the 'androgenic' potency of the steroids, and the possible use of this response for the assay of 'anabolic' steroids is discussed.
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Search for other papers by D. E. WRIGHT in
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SUMMARY
[7α-3H]Progesterone was administered to two groups of mice. The localization of radioactivity in tissues was examined by autoradiography and by liquid scintillation counting. Particular attention was paid to the distribution of radioactivity in the liver and biliary system. The greatest amount of administered steroid was taken up by the liver, rapidly secreted into the biliary system and excreted into the gastrointestinal tract. Other tissues, including the uterus, did not take up any appreciable amount of radioactivity, and the autoradiographs showed that radioactivity was not associated with any particular region of hepatic and other cells. The biological half-life of radioactivity in the blood was 11 min in animals given labelled progesterone intravenously.
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SUMMARY
The uptake of glucose by isolated rat diaphragm is increased in vitro by serum from normal oxen and diabetic patients treated with ox insulin; by slower moving albumin, β- and γ-globulin fractions of serum from normal oxen; by slower moving albumin, α2-, β- and γ-globulin fractions of serum from treated diabetics (prepared by zone electrophoresis on columns of treated cellulose). More rapidly moving albumins from both types of serum did not stimulate glucose uptake. The effect of serum or protein fractions of serum was absent or markedly reduced in the presence of antiserum to ox insulin prepared in guinea-pigs. It is concluded that the stimulating effect of serum and protein fractions of serum on uptake of glucose by diaphragm is due to circulating insulin.
The effect of insulin on uptake of glucose by diaphragm is shown to be potentiated by the presence of corticotrophin, prolactin, normal guinea-pig serum and an albumin preparation from the serum of hypophysectomized rats.
The significance of these results in relation to the detection and assay of insulin in blood with isolated diaphragm and to the transport of insulin in blood is discussed.