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J R Turtle

Publications and source records attributed to J R Turtle.

At least 37 records · Page 2Linked to original sources
PubMed1990

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↗
PubMed1990

The role of calcium in insulin release from the human fetal pancreas.

Previous experiments have established that the human fetal pancreas is relatively unresponsive to glucose as regards insulin release, but will secrete this hormone when exposed to agents which increase levels of cAMP or which activate protein kinase C. The current experiments were designed to establish which role another major stimulus, calcium, had in the release of insulin from this organ. For this purpose, cultured explants of human fetal pancreas were exposed to stimuli either in static or dynamic stimulation. The data show that insulin release is enhanced in the presence of 10 mM Ca2+, as well as the calcium ionophores A23187 and ionomycin, the latter agent being effective only if extracellular Ca2+ was present. A biphasic response was seen for Ca2+ but only a second phase response for A23187. Voltage-dependent calcium channels were shown to be present by the ability of the calcium channel blocker, verapamil, to inhibit insulin release caused by an agent that depolarizes membranes, potassium. The essential role of extracellular calcium in the insulinogenic effect of agents which increase cAMP levels--theophylline--and which activate protein kinase C--12-O-tetradecanoylphorbol-13-acetate--was demonstrated by showing (a) partial inhibition of insulin secretion by calcium channel blockers, (b) no enhancement of insulin release in the absence of extracellular calcium and (c) greater enhancement of insulin release in the presence of the calcium channel activator BAY-K-8644, which caused no stimulation by itself. These data put into better perspective our understanding of the mechanisms involved in insulin release from the human fetal pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport, Active↗
PubMed1990

The effects of dietary n - 3 fatty acid in animal models of type 1 and type 2 diabetes.

We studied the incorporation of dietary n - 3 fatty acids from marine oils into red cell membranes, using animal models of type 1 diabetes (streptozotocin-treated Wistar rats) and type 2 diabetes (gold-thioglucose-injected CBA/T6 mice). In type 1 diabetic rats, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were higher following marine oil supplementation, and the increase in EPA was significantly greater than in non-diabetic animals (3.4 +/- 1.4% vs. 0.8 +/- 1.6%). Marine oil supplementation also resulted in higher levels of EPA and DHA in mice, but the increases were quantitatively similar with and without type 2 diabetes. Improvement in glycosylated haemoglobin following n - 3 fatty acid feeding was only found in type 2 diabetes (6.5 +/- 2.9% vs. 9.5 +/- 1.2%). This was associated with a higher plasma insulin concentration (170 +/- 40 vs. 136 +/- 41 mU/ml). The theory that n - 3 fatty acids improve insulin sensitivity would have predicted a decrease in plasma insulin levels. Our results suggest that n - 3 fatty acids may modify insulin secretion.

Animals↗
PubMed1990

Abnormalities of ascorbic acid metabolism and diabetic control: differences between diabetic patients and diabetic rats.

Ascorbic acid is required in the synthesis of collagen and is also an important anti-oxidant. In a previous study, plasma ascorbic acid concentration was found to be decreased in diabetic patients but there was no relationship with blood glucose level. In the current study of diabetic patients, both plasma ascorbic acid and its urinary excretion correlated inversely with glycosylated hemoglobin level. Plasma ascorbic acid was also lower in diabetic rats but urinary ascorbic acid was elevated. The divergent trend in urinary ascorbic acid excretion observed in diabetic patients and diabetic rats may be due to difference in the ability of these two species to synthesize ascorbic acid. Difference in renal reabsorption of ascorbic acid may also be a relevant factor. The lower plasma and urinary ascorbic acid levels in diabetic patients with more severe hyperglycaemia indicates that this group of patients is particularly at risk of developing deficiency of this vitamin. As ascorbic acid has many important functions in the body, it may be necessary to supplement this vitamin in patients with chronically poorly controlled diabetes.

Adult↗
PubMed1990

Knowledge and attitude change as predictors of metabolic improvement in diabetes education.

Randomized trials of formal diabetes education have proven that education in isolation from other aspects of diabetes care has limited impact on metabolic control through the simple transfer of information. Comprehensive programme evaluation requires assessment of the process by which knowledge and attitude change affect subsequent control of diabetes. This study examined the impact of a formal diabetes education programme on diabetes-specific knowledge and attitude, and the relationship between these characteristics and metabolic control of the disease over a 15-month period. Knowledge and attitude were assessed using parallel forms of the DKN and ATT39 scales presented randomly as pre-test and post-test to 309 patients attending a 2-day diabetes education programme. Mean knowledge scores increased by 25% (P less than 0.0001) and standardized ATT scores showed a small but significant positive shift after the programme (P less than 0.01) and remained stable in a subset of 177 patients at 3-month follow-up. ATT scores showed a marked convergence towards normal during the intervention (ANOVA, P less than 0.0001). Glycosylated haemoglobin (HbAlc), a medium-term measure of blood glucose control, was recorded in 209 cases for 6 months preceding the programme, and for 15 months following, at intervals of 3 months. The mean HbAlc improvement, from 11.3 to 9.0% (P less than 0.001), was predicted by stepwise regression from initial diabetes control (57% variance) and psychosocial factors (17% variance) including attitude scores and personality characteristics. Diabetes knowledge did not predict improvement in the control of diabetes.

Adaptation, Psychological↗
PubMed1990

Rural/urban differences of diabetes--impaired glucose tolerance, hypertension, obesity, glycosolated haemoglobin, nutritional proteins, fasting cholesterol and apolipoproteins in Fijian Melanesians over 40.

Two populations of Fijian Melanesians over 40 years of age were compared. The first population was located in a remote rural area and the other in an urban environment. There was no significant difference between the two populations in age, height and diastolic blood pressure. Highly significant differences were observed in mean weight, body mass index, prevalence of impaired glucose tolerance, prevalence of diabetes, mean glycosolated haemoglobin, mean systolic blood pressure, fasting cholesterol, immunological albumin, immunological transferrin, and A1 and B apolipoproteins. The higher value was associated with urban living. Thus urban living is associated with obesity, impaired glucose tolerance, diabetes, higher systolic blood pressure, higher levels of fasting lipids and increased risk factors for cardiovascular disease.

Apolipoprotein A-I↗
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↗