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Biomedical subjects

J R Turtle

Publications and source records attributed to J R Turtle.

At least 127 records · Page 7Linked to original sources
PubMed1981

Insulin inhibition of calcium binding by human placental membrane.

Insulin and its analogues displaced membrane-bound calcium within a physiological range of insulin concentration, in proportion to both biological potency and ability to displace porcine 125 I-labelled insulin from the insulin receptor. Mild tryptic digestion of the membrane reduced insulin binding but did not reduce specific calcium binding. Displacement of membrane-bound calcium by insulin was dependent on insulin binding to its intact receptor. These studies suggest that Ca2"ay exert a controlling influence on insulin-receptor binding in vivo.

Calcium↗
PubMed1981

The effect of fasting on liver receptors for prolactin and growth hormone.

The effects of 3 day fasting on liver prolactin and growth hormone receptors have been investigated in male and female rats. Fasting caused a significant fall in serum immunoreactive insulin (67% decrease), while receptor-reactive somatomedin fell 82% when measured in whole serum and by 72% when measured in serum fractions following gel chromatography at low pH. Tracer ovine prolactin binding to liver microsomal membranes was reduced by 55% on fasting in females, but unchanged in males. Tracer bovine growth hormone binding fell significantly in both sexes. Analysis of competitive binding curves showed the decrease binding to be due to a loss of prolactin receptors in females, and of high affinity (but not low affinity) growth hormone receptors in males and females. Significant correlations were seen between serum insulin and tracer prolactin (females) and growth hormone (males and females) binding to liver membranes. Correlations between serum insulin and liver high affinity growth hormone binding sites were particularly significant (r = 0.899 in females, r = 0.910 in males). It is proposed that the hypoinsulinemia of fasting causes a loss of high affinity growth hormone receptors in the liver, which could result in a relative hepatic resistance to growth hormone and a decreased hepatic generation of somatomedin.

Animals↗
PubMed1981

Changes in rat liver prolactin binding sites in diabetes are sex dependent.

The effect of streptozotocin-induced diabetes (100 mg/kg) on lactogenic binding sites, measured by iodinated ovine prolactin (PRL) binding, has been studied in liver microsomal membranes from males and female rats. In females, specific binding was reduced in diabetes from 13% to 4.5% of total tracer, while in males specific binding increased from 0.5% to 2.5%. Similar results were obtained using iodinated human growth hormone as tracer, through overall binding was higher. Scatchard plots of binding curves in females showed that changes in binding were due to changes in receptor concentration, while affinity remained unchanged at 2 X 10(9) M-1. In diabetes, serum PRL and estradiol levels fell by 60% in males but showed no significant change in females, and could therefore not account for receptor changes. In contrast, mean testosterone levels fell in diabetic males from 9.0 to 3.9 nM, and rose in diabetic females from 2.1 to 5.8 nM. Estrogen treatment of male rats caused a marked induction of binding in nondiabetic animals, and a change from the male to the female response to diabetes. Testosterone treatment of nondiabetic females suppressed binding, although not to the male levels, and diabetes caused further suppression. These results are consistent with a role for testosterone in regulating PRL receptors in experimental diabetes, but suggest that other hormonal influences are also involved.

Animals↗
PubMed1981

Testicular function after renal transplantation.

Gonadal function was assessed in seventeen adult male renal transplant recipients, with well established good homograft function, for a mean of 4.9 years. Patients were assessed clinically and by measurement of basal concentrations of FSH, LH, prolactin, testosterone and oestradiol, FSH and LH responses to bolus injections of LHRH and semen analysis. Retrospectively all had symptoms consistent with marked hypogonadism prior to transplantation but in nine out of sixteen this was reversed with transplantation. Residual hypogonadism was evident in seven of sixteen patients and correlated with duration of haemodialysis longer than 1 year (P less than 0.01). Even among patients with clinically normal gonadal function, defects in the hypothalamic--pituitary--testicular axis remained. Elevated basal serum FSH, excessive FSH responses to LHRH and lowered basal serum testosterone were found. In the group with residual hypogonadism more marked changes, including elevated basal LH and excessive LH responses to LHRH, were also found. Fertility was recorded in two men on three occasions since transplantation. Sperm counts were normal in five and abnormal in four patients. Testicular volume and sperm density were inversely correlated with basal and stimulated FSH and LH levels.

Adult↗
PubMed1981

Clinical trial of an aldose reductase inhibitor in diabetic neuropathy.

A single-blind, nonrandomized, placebo crossover clinical trial of an aldose reductase inhibitor, Alrestatin (AY 22, 284) was performed over a 4-mo period in nine patients with diabetic peripheral neuropathy. Most patients had subjective benefit, but objective measures of conduction were essentially unchanged. Substantial toxicity was evident, particularly photosensitive skin rash.

Action Potentials↗
PubMed1981

Positive interference by danazol in a testosterone radioimmunoassay kit procedure.

We describe a problem in measuring serum testosterone concentrations in the serum of women who are taking danazol. The Diagnostic Products Corporation testosterone radioimmunoassay gives very high apparent testosterone concentrations in these women and the value obtained depends on the volume of serum extracted per assay tube. Chromatography of the serum extracts on Sephadex LH-20, but not on Celite, before radioimmunoassay reduced these high apparent testosterone concentrations to less than that found in normal women.

Danazol↗
PubMed1980

Association between serum insulin, serum somatomedin and liver receptors for human growth hormone in streptozotocin diabetes.

Streptozotocin-induced diabetes in the female rat caused a decrease in the serum level of somatomedin (Sm), measured by radioreceptor assay. The decrease was reversed by insulin therapy. In diabetes of varying severity, serum insulin and Sm levels showed highly significant association up to the insulin concentration (18 microU/ml) corresponding to normal serum Sm (1 U/ml). Similarly, the hepatic binding of human growth hormone (hGH) showed highly significant association with serum Sm levels up to the degree of binding (7% of tracer) corresponding to normal serum Sm. Binding of hGH to normal liver was about 12% of tracer. These results suggest that insulin might regulate serum Sm via its effect on liver lactogenic receptors, and that about half of these receptors are "spare", or in excess of those required to maintain normal serum Sm levels.

Animals↗
PubMed1980

Somatogenic receptors of rat liver: regulation by insulin.

Somatogenic (i.e. GH) receptors have been studied on liver microsomal membranes from male and female rats. Tracer bovine GH was displaced from its binding sites by GHs of various species, but was displaced only weakly by PRLs. Specific bovine GH binding was 3.5-fold higher to female rat liver membranes than to membranes from males. Streptozotocin-induced diabetes significantly reduced binding, by 80% in females and 50% in males, while insulin therapy to normalize weight gain reversed the decrease in binding. Competitive binding curves were consistent with two independent classes of binding site: low affinity sites with K equal to 0.5 nm-1 in both sexes, and high affinity sites with K equal to 12.1 nm-1 in males and 21.4 nm-1 in females (P less than 0.001). The addition of excess ovine PRL caused a substantial loss of high affinity binding with little loss in the low affinity region, suggesting a weak somatogenic role for ovine PRL. In diabetic animals, low affinity sites were unchanged from normal, while high affinity sites were decreased in number, with no change in affinity, and restored on insulin therapy. Serum immunoreactive rat GH levels were the same in normal and diabetic, male and female animals. These studies suggest that the apparent hepatic resistance to GH seen in diabetes when liver somatomedin release is low despite normal serum GH might be explained by the loss of GH receptors in this condition.

Animals↗
PubMed1980

Perifusion and culture of human fetal pancreas.

Human fetal pancreas has been obtained after the therapeutic termination of pregnancy with prostaglandin F2 alpha. Pancreatic explants were studied in a perifusion system and maintained in organ culture for up to 3 wk. Insulin biosynthesis was stimulated by glucose; however, the incorporation of 3H-L-leucine into proinsulin was surprisingly high (52% after 3 h) vs. insulin (48%), which suggests a possible block in the conversion of proinsulin to insulin. Insulin secretion was stimulated during perifusion with 19.3 mM glucose (1.6 X prestimulation level), 1.5 microM glucagon (2.4), 5mM leucine (2.4), 10 mM arginine (2.7), and 10 mM theophylline (10.0). Insulin biosynthesis and secretion were maintained in organ culture. After 12 days there was a 3.4-fold increase in insulin secretion in the presence of 22 mM glucose compared with 5.5 mM glucose, and the explant insulin content rose in the presence of high glucose levels by 89%. The acute insulin secretory response to 10 mM theophylline was maintained after culture. These studies suggest that human fetal pancreas should be considered as a potential source of donor tissue for pancreas transplantation in human diabetes.

Cycloheximide↗
PubMed1980

Receptors for insulin and insulin-like molecules.

An increasing body of evidence supports the regulation of hormone action by changes in receptor concentration and affinity. Down and up regulation of insulin and somatomedin receptors by changes in hormone concentration explains the alterations in receptor numbers in obesity or diabetes. However, the changes in receptor affinity that have been described have no known mechanism. In most cases, they occur in vivo, but changes can be produced in vitro by ketone bodies and calcium ions. Calcium ions have also been implicated in insulin action, thus strengthening this relationship. Evaluation of the control of receptor affinity must take into account the effects of metabolites such as glucose and minerals, as well as multiple other factors. The relationship between binding and the biological effect of insulin has to be resolved before the full understanding of insulin action can be reached. The controversial areas of insulin receptor research are becoming clearer, but much more information is required before these questions can be resolved.

Adrenocorticotropic Hormone↗
PubMed1979

Purification of the insulin receptor from human placental membranes.

Insulin receptors were purified from human placental microsomal membranes by solubilisation with Triton X-100 followed by Sepharose 6B chromatography, phosphate gradient elution from hydroxyapatite and affinity chromatography on concanavalin A-Sepharose. 2000-fold purification was achieved with 63% overall recovery. The purified receptor gave a single band on 3.75% polyacrylamide (0.1% Triton X-100) gel electrophoresis. On sodium dodecyl sulphate-polyacrylamide gel electrophoresis there was a major band at 75,000 and a minor band at 80,000 daltons. The purified receptor rechromatographed on Sepharose 6B with an apparent molecular weight of 300,000.

Female↗
PubMed1979

Decrease in serum receptor-reactive somatomedin in diabetes.

Somatomedin in rat serum has been measured by a sensitive radioreceptor assay using 125I-labelled human somatomedin and human placental membrane. In rats made diabetic with strepotzotocin, receptor-reactive somatomedin levels were decrease by up to 75%. The decrease followed the time course of increasing serum glucose and occurred to the same extent in rats aged between 4 and 40 weeks. Endogenous serum receptor-reactive somatomedin appeared exclusively in high molecular weight fractions on gel chromatography. In diabetes the decreased somatomedin was due to a fall in this high molecular weight activity, but was not accompanied by a fall in somatomedin binding protein. These results suggest a role for insulin in maintaining serum somatomedin levels.

Animals↗
PubMed1979

Treatment of acromegaly with bromocryptine.

Twelve acromegalic patients with clinical and biochemical evidence of active disease were studied whilst on bromocryptine (Sandoz) at a maximum dosage of 10--60 mg. The patients were followed for a period of 9--23 months. Clinically, ten patients showed a reduction or disappearance of sweating and seven patients had a reduction in soft tissue mass. Of the five patients who had diabetes prior to treatment, three reverted to normal glucose tolerance during treatment. Biochemically, there was no difference between mean plasma levels of growth hormone (hGH) before and on maximum therapy with bromocryptine. There was a significant difference between fasting plasma hGH before treatment with bromocryptine and following treatment for 9--23 months in five individual patients. Side effects were not disabling in this series except for a reversible paranoid psychosis in one patient. The overall results are disappointing; although some clinical features improved, plasma hGH levels returned to normal in only three patients. Bromocryptine has a limited place in the management of acromegaly for those patients in whom conventional therapy has been ineffective or is contraindicated.

Acromegaly↗
PubMed1978

Treatment of acromegaly with bromocriptine.

Twelve patients with acromegaly were treated with bromocriptine for periods from nine to 23 months. All showed some clinical improvement. There was no significant difference in plasma growth hormone levels before and after therapy with bromocriptine, but a significant fall in plasma prolactin levels was observed after the bromocriptine therapy was commenced. The release of other pituitary hormones was not affected by bromocriptine.

Acromegaly↗