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Biomedical subjects

J R Turtle

Publications and source records attributed to J R Turtle.

At least 37 records · Page 2Linked to original sources
PubMed1989

Streptozotocin is not toxic to the human fetal B cell.

It has been generally assumed that because streptozotocin is toxic to the adult B cell of most species, it should also damage B cells obtained at earlier stages of development. This paper examines whether this is true for human fetal pancreata obtained from the therapeutic termination of pregnancies during the first half of the second trimester. Experiments were carried out both in vivo and in vitro. For the former experiments diced explants of the human fetal pancreas were grafted beneath the renal capsule of nude mice 3 weeks before streptozotocin was administered to make the animals diabetic. The grafts were removed 1 week, 2-4 weeks or 3 months later, and were found to be of similar weight and insulin content to the control grafts. In 2 of the animals with grafts remaining for 3 months the diabetes had even been reversed by the implant, hyperglycaemia recurring when the graft was removed. In contrast, rat fetal pancreata grafted beneath the renal capsule of nude mice, subsequently rendered diabetic, were adversely affected by streptozotocin, the insulin content of the implants being 12% of levels in control grafts. Adequate uptake of streptozotocin by the implanted human fetal pancreas was established by measuring tissue levels of the drug 30 min after its injection. Histological examination of the grafted human fetal pancreas showed no deleterious effect of streptozotocin on the number of granulated B cells one day after injection, although by this time the host was diabetic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effect of normoglycemia on the functional maturation of the human fetal beta cell.

Previous studies from this laboratory have shown that human fetal pancreas of gestational age 14-20 weeks was capable not only of growing but also of maturing in its insulinogenic response to an acute static challenge with glucose, once it was removed from its usual physiological environment and passaged for up to 37 weeks in the diabetic nude mouse (absolute age of 58 weeks, where absolute age = gestational age + duration of passage in the mouse). In order to analyze the dynamics of insulin secretion during this process of maturation, these experiments were repeated, the tissue being perifused after removal from the mouse. Normoglycemic nude mice rather than diabetic ones were used because of their hardier nature. Human fetal pancreata of gestational age 14-20 weeks were passaged in these normoglycemic animals, either subcutaneously or beneath the renal capsule, for 11 to 70 weeks (absolute age up to 86 weeks). The tissue was removed and, after a mean of 1 day in organ culture, perifused for 50 min with 20 mmol/L of glucose. While overall there was a slight but significant increase in insulin secretion over basal levels, there was no time-dependent maturation of the response to glucose, and no adult-type response at any stage, as occurs both physiologically and in tissue passaged in the diabetic nude mouse by this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The effect of improved control on blood filtration properties and non-enzymatic glycosylation of erythrocyte proteins in type 2 diabetes.

Abnormal blood flow in the microcirculation has been reported in diabetes and may be important in the pathogenesis of diabetic complications. The mechanism of this is not understood but non-enzymatic glycosylation of erythrocyte membrane or haemoglobin causing reduced erythrocyte deformability and a secondary change in filtration properties of blood have been suggested as possible factors. The relationship of non-enzymatic glycosylation of erythrocyte membrane and glycosylated haemoglobin to filtration time of blood was investigated during stabilization of diabetes with sulphonylurea therapy. Over an 8-month period, glycosylated haemoglobin, non-enzymatic glycosylation of erythrocyte membrane, and filtration time fell by 41%, 71%, and 53% of the initial value, respectively, but the rate of decline was slower for filtration time which did not change significantly until the last month. Due to the different time-course of improvement, no relationship was found between filtration time and glycosylated haemoglobin or non-enzymatic glycosylation of erythrocyte membrane whereas glycosylated haemoglobin and non-enzymatic glycosylation of erythrocyte membrane correlated significantly (r = 0.49, p less than 0.001). These results suggest that the abnormal filtration property of blood in diabetes is not a direct consequence of non-enzymatic glycosylation, and suggest that the erythrocytes made in the hyperglycaemic milieu are abnormally rigid. The filtration properties of blood are only improved when new generations of erythrocytes enter the circulation.

Diabetes Mellitus, Type 2↗
PubMed1989

Anti-smoking programme for diabetic patients: the agony and the ecstasy.

It is generally accepted that people with diabetes should be encouraged to abstain from smoking but there are few data on the best strategy to implement this. In a preliminary survey of our diabetic patients, knowledge of the general and specific health effects of smoking was poor. In a prospective study of 70 diabetic smokers, only 50% agreed to participate in an anti-smoking programme, and the drop-out rate was high irrespective of whether the content of the programme was general or specific for diabetes. The enrollment rate was best 2 months after the diagnosis of diabetes and the drop-out rate was highest in patients recruited immediately following diagnosis. According to self-reported data, cigarette consumption fell after the first session of the anti-smoking programme but this could not be verified by the measurement of plasma cotinine. It is concluded that an anti-smoking counselling programme based on provision of information, within the context of a specialized diabetes centre, is not cost-effective.

Cotinine↗
PubMed1989

Adrenal function in patients with active tuberculosis.

Although tuberculosis is a recognised cause of adrenal insufficiency, little is known about adrenal function in patients with active tuberculosis. Ninety Melanesian adults with active tuberculosis (30 pulmonary, 30 miliary, 30 extrapulmonary) had adrenal function assessed prospectively before and three to four weeks after starting antituberculous chemotherapy. Basal serum cortisol concentrations were normal in 55 (61%) and raised in 35 (39%) of the subjects. No patient had a low basal cortisol concentration. After Synacthen stimulation, cortisol responses were normal in 81 (92%) of the patients and subnormal in seven (8%). After antituberculous chemotherapy the response to Synacthen stimulation was normal in all but one patient. It is concluded that adrenal dysfunction is an uncommon problem in patients with active tuberculosis, and that, contrary to recent reports, antituberculous chemotherapy regimens that include rifampicin do not have an adverse effect on adrenal function.

Adrenal Glands↗
PubMed1989

Ascorbic acid metabolism and polyol pathway in diabetes.

It has been reported previously that the plasma concentration of ascorbic acid (AA) is reduced in streptozocin-induced diabetic rats and can be normalized by treatment with the aldose reductase inhibitor tolrestat. This study was designed to investigate further the relationship between the polyol pathway and AA metabolism in diabetic rats. Disturbance of AA metabolism was demonstrable after 1 wk of diabetes. Dietary myo-inositol supplementation was effective in normalizing plasma AA levels, as was treatment with tolrestat. In untreated diabetes, despite low plasma AA concentration, there was increased urinary excretion of AA that was reversed by treatment with either tolrestat or myo-inositol. In contrast, AA supplementation normalized plasma AA concentrations while further increasing urinary AA excretion. The abnormality of AA metabolism was less severe in galactose-fed rats, which had normal plasma AA levels and only minor increases in urinary AA excretion. These studies demonstrated a disturbance in the regulation of plasma and urinary AA concentration in experimental diabetes and confirmed the relationship of AA with the polyol pathway. Because AA has many important biological functions, abnormalities of AA metabolism could be important in the pathogenesis of some diabetic complications. The interaction of the polyol and AA pathways suggests that this could be another site of action for aldose reductase inhibitors.

Aldehyde Reductase↗
PubMed1988

Chronic stimulation of human fetal pancreas with phorbol inhibits insulin secretion.

Acute exposure to agents that activate protein kinase C is known to cause insulin release both from the fetal and adult pancreas. These experiments were designed to test the effect of chronic exposure of the human fetal pancreas to such agents. Nine to twelve days after commencement of culture of this tissue, exposed to 0.165-1.3 microM 12-O-tetradecanoylphorbol-13-acetate, insulin secretion was reduced and remained less than that for controls thereafter. Exchange of the test for the control medium resulted in partial recovery of insulin release. Insulin content of the treated explants was also significantly reduced. The insulinogenic response to an acute challenge of either 20 mM glucose or 10 mM theophylline/2.8 mM glucose at the end of the culture was no different from that for controls.

Enzyme Activation↗
PubMed1988

Proteinuria and renal function in diabetic patients fed a diet moderately restricted in protein.

Protein restriction has been used in the treatment of renal disease and may also be beneficial in the management of diabetic nephropathy. We evaluated the effects of moderate protein restriction (0.6 g/kg ideal body weight per day) for a 3-mo period on renal function in seven diabetic patients. Moderate protein restriction led to a decrease of approximately 50% in the albumin excretion rate in patients with overt proteinuria or microalbuminuria. This decrease occurred in some patients without a decrease in glomerular filtration rate, renal plasma flow, or plasma albumin concentration and may reflect subtle changes in filtration properties or permeability of glomeruli. In this pilot study moderate protein restriction has marked effects on albumin excretion irrespective of the initial degree of renal impairment. It is therefore suitable for longer-term study of its effects on the progression of renal disease in both patients with overt and incipient diabetic nephropathy.

Adult↗
PubMed1988

Activators of protein kinase C stimulate insulin secretion from the human fetal pancreas.

The human fetal pancreas, like the adult pancreas, releases insulin in response to agents that increase intracellular levels of calcium and cyclic AMP. It differs from the adult pancreas in that glucose causes either minimal or no insulin secretion from it. Whether activation of protein kinase C will cause release of insulin from this immature cell, as it does from the adult pancreas, is unknown. This was the phenomenon examined in the experiments below. Activators of protein kinase C, 1.3 microM 12-O-tetradecanoylphorbol-13-acetate (TPA) and 25.1 microM 1-oleoyl-2-acetylglycerol, caused significant release of insulin from cultured explants of human fetal pancreas. Lower concentrations of TPA--0.65 microM or less--had no such effect. Agents that are known to inhibit protein kinase C, 100 microM 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, 2 mM polymyxin B, and 1 mM dibucaine, caused abolition of the insulinogenic effect of 1.3 microM TPA. Glucose, at 2.8, 5, and 10 mM, also inhibited the positive effect of TPA. However, when the concentration of glucose was increased to 20 or 30 mM, stimulation of insulin secretion returned to levels achieved with TPA alone. These levels were significantly higher than the minimal response achieved with 20 mM glucose. Such data support the involvement of protein kinase C activation in insulin secretion from the human fetal pancreas. It is postulated that this involvement may occur physiologically.

Enzyme Activation↗
PubMed1988

Recovery of human fetal pancreas after one year of implantation in the diabetic patient.

Between one and six cultured human fetal pancreata were allografted into five insulin-dependent diabetic recipients and their progress monitored for a year on each occasion. To prevent rejection the tissue was cultured for 1-3 weeks before transplantation, the HLA-DR antigens of the donor tissue were matched with those of the recipient when a single pancreas was used, and four of the recipients were immunosuppressed, three because of coexisting renal grafts. Graft function was observed transiently in one of the recipients. In three others human fetal pancreas was recovered 9-14 months after transplantation, although it was being slowly rejected during this time. Beta cells were present in the graft but did not function adequately to enable immunoreactive C-peptide to be measured in peripheral blood. The issues of rejection and immaturity of the human fetal pancreas will need to be surmounted if the potential of the human fetal pancreas to normalize blood glucose levels in diabetic man is ever to be realized.

C-Peptide↗
PubMed1988

Deficiency of ascorbic acid in experimental diabetes. Relationship with collagen and polyol pathway abnormalities.

The plasma and tissue concentration of ascorbic acid (AA) is reduced in diabetes. This study was designed to investigate the mechanism and significance of this phenomenon. The low plasma AA concentration of diabetic rats can be normalized by dietary AA supplement (20-40 mg/day), a dosage approximately equal to the maximal synthetic rate of this substance in the rats. Treatment of diabetic rats with this regime prevented the decrease in activity of granulation tissue prolyl hydroxylase (PRLase), an AA-dependent enzyme required for maintaining the normal properties of collagen. The decreased plasma AA concentration and granulation tissue PRLase activity in diabetes can also be normalized by the aldose reductase inhibitor tolrestat. We conclude that in diabetic animals there is a true deficiency of AA that may be responsible for some of the changes of collagen observed in diabetes. Treatment with AA or an aldose reductase inhibitor may prevent some of the diabetic complications with underlying collagen abnormalities.

Aldehyde Reductase↗
PubMed1988

Comparison of different models of diabetes care on compliance with self-monitoring of blood glucose by memory glucometer.

The modern management of diabetes relies heavily on self-monitoring of blood glucose (SMBG), and therefore SMBG records are an important source of clinical data for management decision making. The development of a memory Glucometer has provided the opportunity to verify the validity of glucose records thus generated and observe the effects of different educational approaches on compliance with SMBG. Thirty-four patients without previous experience of SMBG were randomized into one of the following experimental groups differing in the model of diabetes care: mutual decision making, didactic, and authoritarian. Patients, unaware of the memory capacity of the glucose meter, were required to perform four glucose measurements per day over a 14-day observation period. Patient-generated blood glucose records were then compared with objective records stored in the glucose-meter memory. Patients with gestational diabetes mellitus recorded a lower proportion of correct results (63 vs. 79%, P = .049) and exhibited a tendency to invent results with lower blood glucose levels (5.3 vs. 7.5 mM, P less than .0001) than the results omitted compared with patients with non-insulin-dependent diabetes mellitus. Predictors of greater validity of records were perceived intelligence of the subject (chi 2 = 4.56, P less than .02) and private health-insurance status (chi 2 = 4.52, P less than .04), whereas the experimental group assignment was not significant. These findings reflect potential motivational and sociodemographic limitations in the validity of SMBG recordings within the management and education of patients with gestational and nongestational diabetes.

Blood Glucose Self-Monitoring↗
PubMed1987

The activity of the pyruvate dehydrogenase complex in heart and liver from mice during the development of obesity and insulin resistance.

The amount of pyruvate dehydrogenase in the active form (PDHa) was increased 1.7-fold compared with controls in heart muscle of mice 1 week after induction of obesity with a single injection of gold-thioglucose. At 4 weeks post injection, the amount of PDHa was decreased to 32% of control, a value which was observed in later stages of the obesity syndrome. In contrast, liver PDHa was increased and remained at an increased activity during the development of obesity. Despite normal post-prandial serum insulin contents, liver membrane insulin-receptor numbers were decreased 1 week after gold-thioglucose injection, and there was no change in receptor affinity. The decrease in heart PDHa in the obese animals was reversed by a single dose of 2-tetradecylglycidic acid, but this inhibitor of mitochondrial fatty acid oxidation did not affect liver PDHa in these animals. These early and diverse changes in PDHa argue for a multifactorial aetiology in the development of the whole-body insulin resistance seen in older gold-thioglucose-treated obese animals.

Animals↗