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Biomedical subjects

J R Turtle

Publications and source records attributed to J R Turtle.

At least 19 recordsLinked to original sources

The effects of fasting and refeeding on liver glycogen synthase and phosphorylase in obese and lean mice.

The responses of hepatic glycogen synthase and phosphorylase to fasting and refeeding were assessed as part of an investigation into possible sites of insulin resistance in gold thioglucose (GTG) obese mice. The active forms glycogen synthase and phosphorylase (synthase I and phosphorylase a) and the total activity of these enzymes were estimated in lean and GTG mice over 48 h of food deprivation, and for 120 min after glucose gavage (1 g/kg wt). In lean mice there was a maximal reduction in hepatic glycogen content after 12 h of starvation and the activity of phosphorylase a decreased from 23.8 +/- 1.9 to 6.8 +/- 0.7 mumol/g protein/min. These changes were accompanied by an increase in the activity of synthase I (from 0.14 +/- 0.01 to 0.46 +/- 0.04 mumol/g protein/min). In obese mice, similar changes in enzyme activity occurred after 48 h of starvation. These changes were accompanied by a significant reduction in the hyperinsulinemia and hyperglycemia of the GTG mice. After glucose gavage in both lean and obese mice, the activity of synthase I further increased over the first 30 min and declined thereafter. The activity of phosphorylase a increased progressively after refeeding. Results from this study suggest that despite increased hepatic glycogen deposition, the responses of glycogen synthase and phosphorylase, in livers of obese mice, to fasting and refeeding are similar to those of control mice even in the presence of insulin resistance.

Animals

Diabetes education: whose priorities are met?

Two hundred Type 2 diabetic patients newly referred to the diabetes centre at a large university teaching hospital were studied over an 8-month period. Patients completed a diabetes knowledge questionnaire, and specified their educational priorities by selecting six diabetes-related topics from a list of 14. After giving 1 h of individual education and using the same list, the educators selected six topics which they considered to be most important for that particular patient to know. Choice of educational priorities differed between the patients and the corresponding educator (p less than 0.001). In only 38% of cases did the educators' first three priorities coincide with those of the patients. The major discrepancies were in the selection of 'sick day management' and 'complications', especially favoured by patients, as against 'oral hypoglycaemic agents' and other therapy-related topics, especially favoured by educators. Diabetes knowledge was a determinant of educational priority for patients (p less than 0.001) but not educators. In contrast, only the educators' overall choices were affected by duration of diabetes (p less than 0.001). Diabetes treatment type influenced both patients' and educators' selection of priorities (p less than 0.001). We conclude that an educational strategy which relies on health professionals' perceptions to determine what diabetic patients need to know may be inadequate.

Blood Glucose

Changes in hepatic glutathione metabolism in diabetes.

Glutathione is important in the regulation of the redox state, and a decline in its tissue level has often been considered to be indicative of increased oxidative stress in diabetes. In this study of diabetic rats, the level of hepatic glutathione was normal unless food intake was restricted. Thus, the previous report of a reduction in hepatic glutathione in diabetes is likely to be the result of food deprivation rather than diabetes alone. In contrast to changes characteristic of oxidative stress, the efflux of glutathione in bile from diabetic animals was significantly decreased, whereas hepatic mixed disulfides were unchanged, and the hepatic gamma-glutamyltransferase activity was considerably increased. These changes were not reproduced by food deprivation. The decrease in biliary excretion of glutathione in diabetes may reflect an attempt to conserve glutathione by activation of the hepatic gamma-glutamyl cycle. We conclude that the disturbances of glutathione metabolism in diabetes are not typical of those seen in oxidative stress or food restriction.

Animals

High affinity insulin binding and insulin receptor-effector coupling: modulation by Ca2+.

Insulin binding and insulin stimulated amino acid and glucose uptake were determined in cultured HTC hepatoma cells in the presence of Ca2+ and ruthenium red (RR) in order to further characterise the putative calcium binding site on the receptor. These ions increased insulin receptor high affinity binding and the sensitivity of these responses to insulin. The insulin concentration required to half-maximally stimulate amino acid uptake decreased significantly from 26.9 +/- 5.8 ng/ml to 6.0 +/- 1.3 ng/ml in the presence of 10 mM Ca2+ and to 1.3 +/- 0.5 ng/ml in the presence of RR. The effect of Ca2+ and RR was more pronounced on insulin stimulated glucose uptake. These agents also increased receptor-effector coupling, reducing the percentage of occupied receptors required for maximal insulin stimulation of amino acid uptake from 10.8% in control cells to 3.4 and 1.4% in the presence of Ca2+ and RR respectively. The receptor occupancy required to produce maximal insulin responses on glucose uptake decreased from 20% (control) to 3.8% (Ca2+ and RR). We hypothesize that since Ca2+ and RR have similar effects, that occupation of Ca2+ binding sites on the receptor produces a conformational change in the insulin receptor which increases insulin receptor affinity, insulin sensitivity and acts on an early post-receptor event responsible for coupling binding to insulin action.

Amino Acids

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

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

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

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

Stimulation of protein synthesis in isolated hepatocytes by somatomedin.

Insulin (1 mU/ml) stimulated the incorporation of 14C-leucine into trichloroacetic acid-precipitable material by isolated hepatocytes from normal and hypophysectomized adult rats and 12-day-old rabbits. Somatomedin (200 ng/ml) purified from human plasma had an insulinlike effect in hepatocytes from hypophysectomized rats and baby rabbits but not from normal rats. This study suggests that, as well as being a site of somatomedin synthesis, the liver may be a target organ for this hormone.

Animals

C-peptide secretion and insulin antibodies as determinants of stability in diabetes mellitus.

The relative significance of residual beta-cell secretory activity and human insulin antibodies in determining diabetic stability has been examined in 35 diabetic subjects. The response of plasma C-peptide immunoreactivity following 50 g oral glucose has been used as an index of beta-cell function. Glucose-stimulated C-peptide secretion was observed in 58% of stable diabetics, but in no labile diabetics. When present, C-peptide secretion following a glucose load in diabetics was of smaller amplitude and slower in onset, but more prolonged than in normal subjects. In secretors, stability of diabetes was significantly correlated with the magnitude of the C-peptide response. As a group, labile diabetics had lower insulin antibody levels than stable patients, but stability and antibody levels were not correlated in individual patients. In non-secretors there was no difference in antibody levels between the stable and labile groups. Neither the equilibrium binding affinities nor the dissociation rate constants differed significantly for antibodies from stable and labile diabetics. Thus stability of diabetes depends upon residual beta-cell secretory activity, but not on the concentration or binding characteristics of insulin antibodies.

Adolescent

Plasma gonadotrophins and LHRH infusions in anorexia nervosa.

Nine female patients with anorexia nervosa were studied, three of them at different stages of weight gain. Basal plasma LH (luteinising hormone) was depressed in emaciated patients, but basal plasma FSH (follicle stimulating hormone) was normal. LH was significantly lower in patients who had been amenorrhoeic for less than 24 months than in those whose amenorrhoea was of longer duration. LH and FSH levels were stimulated by LHRH (luteinizing hormone releasing hormone), infused at a rate of 0.5 microgram/min for four hours. One patient, tested at 60% of standard weight, had no LH response. In all other patients below 70% of standard, the maximal LH response occurred within the first hour of infusion. In patients at higher weights, the LH response was biphasic, and the maximal level was reached during the last hour of the infusion. The FSH response, similarly, approached maximal during the first hour in patients below 70% of standard, but continued to rise throughout the infusion in patients at higher weights. Body weight expressed as a percentage of standard correlated significantly with both phases of the LH response, but not with the FSH response. Most previous authors have found an association between low body weight and depressed pituitary gonadotrophins in anorexia nervosa. The present findings further elucidate this relationship.

Adolescent

Colonic and oesophageal disturbance in a patient with multiple endocrine neoplasia, type 2b.

We report the illness of a 32-year-old male with the syndrome of multiple endocrine neoplasia, type 2b, which comprises medullary carcinoma of the thyroid, phaeochromocytoma, oral mucosal neuromas and skeletal deformity. The patient also had evidence of ganglioneuromatosis of the alimentary tract, a finding which is held to be responsible for constipation and a number of the other gastrointestinal manifestations of the MEN, 2b. Dysphagia, which has not been previously reported in the syndrome was also present. Investigations of the oesophagus which included endoscopy, radiology and a motility study support the diagnosis of achalasia as the cause of the dysphagia.

Adrenal Gland Neoplasms