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R C Turner

Publications and source records attributed to R C Turner.

At least 163 records · Page 9Linked to original sources
PubMed1987

Islet amyloid formed from diabetes-associated peptide may be pathogenic in type-2 diabetes.

Pancreatic islet amyloid deposits were found in 22 of 24 type-2 diabetic subjects (aged 48-68 years) and were not present in 10 age-matched controls. A novel peptide, 37 aminoacids long, termed diabetes-associated peptide (DAP), has been identified in amyloid-containing pancreatic extracts from 3 type-2 diabetic patients but not in extracts from 6 non-diabetic subjects. DAP has major homology with calcitonin-gene related peptide (CGRP) and the islet amyloid of all 22 diabetics showed CGRP immunoreactivity. The immunoreactivity was inhibited by preabsorption of three different CGRP antisera either with CGRP carboxyterminal peptide 28-37 or with extracted DAP. Both diabetic and non-diabetic subjects had CGRP/DAP immunoreactivity in islet B-cells. Electron microscopy of islets containing amyloid indicated fibrillar amyloid between the endocrine cells and capillaries, usually penetrating into deep invaginations of the plasma membrane of the B-cells. These results suggest that islet amyloid contains DAP, which may originate from B-cells. Accumulation of amyloid in islets is likely to impair islet function and may be a causal factor in the development of type-2 diabetes.

Aged↗
PubMed1987

Type II diabetes of early onset: a distinct clinical and genetic syndrome?

The inheritance of non-insulin-dependent (type II) diabetes was studied by a continuous infusion of glucose test in all available first degree relatives of 48 diabetic probands of various ages and with differing severity of disease. In an initial study of 38 type II diabetic subjects and their first degree relatives six islet cell antibody negative patients with early onset disease (aged 25-40 at diagnosis) were found to have a particularly high familial prevalence of diabetes or glucose intolerance. Nine of 10 parents available for study either had type II diabetes or were glucose intolerant. A high prevalence of diabetes or glucose intolerance was also found in their siblings (11/16;69%). In a second study of the families of a further 10 young diabetic probands (presenting age 25-40) whose islet cell antibody state was unknown a similar high prevalence of diabetes or glucose intolerance was found among parents of the five islet cell antibody negative probands (8/9; 89%) but not among parents of the five islet cell antibody positive probands (3/8;38%). Islet cell antibody negative diabetics with early onset type II disease may have inherited a diabetogenic gene or genes from both parents. They commonly need insulin to maintain adequate glycaemic control and may develop severe diabetic complications. Early onset type II diabetes may represent a syndrome in which characteristic pedigrees, clinical severity, and absence of islet autoimmunity make it distinct from either type I diabetes, maturity onset diabetes of the young, or late onset type II diabetes.

Adult↗
PubMed1987

Hypoglycaemia in African children with severe malaria.

Hypoglycaemia, defined as a plasma glucose concentration below 2.2 mmol/l, developed in 15 of 47 prospectively studied Gambian children with severe chloroquine-sensitive falciparum malaria. 5 of these hypoglycaemic children died compared with 1 in the normoglycaemic group (p = 0.02). In contrast to previous observations in quinine-treated adults, in whom hypoglycaemia was associated with hyperinsulinaemia, plasma concentrations of insulin were appropriately low and plasma ketones were high. Raised plasma concentrations of lactate and alanine suggested impairment of hepatic gluconeogenesis. In African children, hypoglycaemia is an important and treatable manifestation of severe malaria and is unrelated to antimalarial treatment.

Acute Disease↗
PubMed1987

Autoimmunity to insulin receptor and hypoglycaemia in patient with Hodgkin's disease.

A 76-year-old man with fasting hypoglycaemia had impaired in-vitro binding of insulin to erythrocyte receptors. The immunoglobulin fraction of his plasma inhibited binding of insulin to normal donor erythrocytes in vitro. Autoantibodies may have stimulated the insulin receptor and produced hypoglycaemia. Hodgkin's disease developed and may have induced the autoimmunity. The hypoglycaemia did not respond to plasmapheresis or azathioprine alone, but it remitted after the addition of prednisolone, and the erythrocyte receptor binding of insulin became normal.

Aged↗
PubMed1987

Haemolysis affects insulin but not C-peptide immunoassay.

Venous blood was taken at the end of a glucose infusion test in 19 individuals and divided into four aliquots, 3 of which were variably haemolysed by repeated passage through a 23-gauge needle to simulate traumatic venepuncture. Plasma insulin (measured by both a charcoal separation and a double-antibody method), C-peptide, and haemoglobin were measured in each aliquot, and haemolysis was also assessed visibly. A significant loss of immuno-assayable plasma insulin was found in samples with only a trace of visible haemolysis, with up to 90% lost in severely haemolysed samples. Plasma C-peptide was unaffected by haemolysis. This represents an additional advantage for the use of plasma C-peptide in assessing insulin secretion.

C-Peptide↗
PubMed1987

Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients.

Deposition of amyloid in pancreatic islets is a common feature in human type 2 diabetic subjects but because of its insolubility and low tissue concentrations, the structure of its monomer has not been determined. We describe a peptide, of calculated molecular mass 3905 Da, that was a major protein component of amyloid-rich pancreatic extracts of three type 2 diabetic patients. After collagenase treatment, an extract containing 20-50% amyloid was solubilized by sonication into 70% formic acid and the peptide was purified by gel filtration followed by reverse-phase high-performance liquid chromatography. We term this peptide diabetes-associated peptide, as it was not detected in extracts of pancreas from any of six normal subjects. Diabetes-associated peptide contains 37 amino acids and is 46% identical to the sequences of rat and human calcitonin gene-related peptide, indicating that these peptides are related in evolution. Sequence identities with conserved residues of the insulin A chain were also seen in a 16-residue segment. On extraction, the islet amyloid is particulate and insoluble like the core particles of Alzheimer disease. Their monomers have similar molecular masses, each having a hydropathic region that can probably form beta-pleated sheets. The accumulation of amyloid, including diabetes-associated peptide, in islets may impair islet function in type 2 diabetes mellitus.

Aged↗
PubMed1987

Insulin sensitivity and beta-cell function assessed by C-peptide in young adults with cystic fibrosis.

Eight patients with cystic fibrosis (CF) aged 18-34 who had normal random plasma glucose levels were studied with a continuous infusion of glucose with model assessment (CIGMA) and plasma C-peptide to assess beta-cell function, and plasma insulin to assess insulin sensitivity. Two had impaired glucose tolerance, two had impaired beta-cell function and all had normal insulin sensitivity. The results of previous studies suggesting that glucose intolerance is common in CF may reflect the inability of an impaired liver to handle a large oral glucose load. The few CF patients who become diabetic may be those who have a preexisting diabetic trait.

Adolescent↗
PubMed1987

A soluble-phase proinsulin radioimmunoassay and its use in diagnosis of hypoglycaemia.

A soluble-phase proinsulin assay has been developed which does not require solid-phase antibody-binding. A human proinsulin standard curve is prepared in insulin-free and proinsulin-free plasma for comparison with unknown plasma samples. Proinsulin and insulin are bound with excess anti-insulin antiserum, and free C-peptide is removed by charcoal adsorption. The supernatant is then assayed using a routine C-peptide radioimmunoassay which utilises anti-C-peptide antiserum. The sensitivity of the assay (2 standard deviations above zero) is 9 pmol/L using 200 microL plasma sample. The assay is free from insulin cross-reactivity up to 100 mU/L and C-peptide up to 2000 pmol/L. Between-assay CV is 13% at 100 pmol/L. The assay has been used in subjects with hypoglycaemia of various aetiologies and has shown that a raised plasma proinsulin in the presence of hypoglycaemia can occur in sulphonylurea-induced and reactive hypoglycaemia as well as in insulinomas. After hyperglycaemic clamps at 7.5, 10 and 15 mmol/L glucose, type II diabetics both on and off sulphonylurea, were found to have lower proinsulin concentrations compared with normal subjects, commensurate with the diabetics' lower insulin responses.

Adult↗
PubMed1987

Greater in vivo than in vitro pulsatility of insulin secretion with synchronized insulin and somatostatin secretory pulses.

To examine the control of pulsatile insulin secretion by an intrapancreatic pacemaker, samples at minute intervals were taken from the portal vein in dogs in vivo and from an isolated perfused pancreas preparation in vitro. Anesthetized dogs had high amplitude pulsatile insulin secretion which was not consistently regular. Fourier transform analysis showed dominant 20- and 10-min periods of spectral power (P less than 0.01). After vagotomy, the relative oscillatory power was reduced from 83% to 42%, about a lower mean concentration with abolition of the 20-min oscillations. The isolated perfused dog pancreas also had oscillatory insulin secretion with oscillatory power of 12%. Autocorrelation showed regularity of in vitro insulin secretion with a period of 10-11 min (P less than 0.0001). In addition, somatostatin was secreted from the in vitro pancreas in pulses in phase with insulin (cross-correlation P less than 0.0001). These data are in accord with the theory that the pancreas has an internal pacemaker which controls insulin secretion, and that the amplitude of the oscillations is modulated by vagal control. The pacing of the islets may be coordinated by a neural network, whereas coincident pulsatile somatostatin release may temporarily suppress islet secretion and help to synchronize hormonal oscillations.

Animals↗
PubMed1987

Normal calcium-activated potassium channel in red cells in type 2 diabetes.

The diminished insulin secretion of type 2 diabetes might result from abnormal regulation of the potassium permeability which leads to beta-cell depolarization. The possibility of a generalized defect has been investigated in vitro by the stimulation of 86Rb efflux from red cells of type 2 diabetic patients by calcium ionophore and its inhibition by quinine. Diabetic subjects and control subjects had identical 86Rb efflux stimulated by 0.2-0.6 microM calcium ionophore A23187 and identical inhibition by quinine with mean Ki 6 microM and 4 microM quinine respectively for 0.2 microM ionophore and mean Ki 38 microM and 37 microM quinine respectively for 0.6 microM ionophore.

Adult↗
PubMed1987

Pancreatic islet amyloid and elevated proinsulin secretion in familial maturity-onset diabetes.

Quantitative morphometry of immunostained pancreatic islet cells in a surgical specimen from a maturity-onset diabetic (MOD) patient (A) has been combined with a study of beta-cell secretion in him and his MOD son (B). The morphometry showed intra-islet amyloid deposits in 24% of islet sections which is a similar distribution to that found in 7 other MODs, (median 24%, range 0-95%). The distribution of islet cells in the pancreas from A was similar to the 7 MODs and 9 age matched non-diabetic subjects (mean beta-cell area per exocrine area, A, 2%; MODs, 1.45%; controls 1.8%). There was a significantly smaller percentage beta-cell area per islet area in A and the other MODs compared to the controls. Beta-cell secretion was studied by an intravenous glucose infusion, 5 mg/kg ideal body wt. min-1 in A and B and 4 other MODs on sulphonylurea or diet therapy. Fasting plasma glucose was high in both A and B (16 and 7.6 mmol/l respectively) in spite of sulphonylurea therapy. Similarly, A and B had elevated fasting plasma levels of insulin, (0.055 and 0.13 pmol/ml respectively) and C-peptide (0.573 and 1.39 pmol/ml respectively). Plasma proinsulin formed a higher percentage of the immunoreactive insulin in fasting plasma samples of both A (36%) and B (43%) than in less hyperglycaemic MODs on diet alone (26%) or sulphonylurea therapy (17%) and the glucose stimulated proinsulin content was even higher (A, 50%; B, 53%; MODs, diet, 19%; sulphonylureas, 16%). Elevated proinsulin levels in a patient with islet-amyloid is consistent with the hypothesis that amyloid may be derived from abnormal beta-cell secretion.

Amyloid↗
PubMed1987

Insulin secretion to glucose infusion in gestational diabetes subjects with differing DNA polymorphisms flanking the insulin gene.

Glucose-stimulated insulin secretion was assessed in relation to the DNA polymorphism flanking the insulin gene in 16 women who had had gestational diabetes. When not pregnant they were studied by a Constant Glucose Infusion for 1 hr with Model Assessment (CIGMA). The patients with either heterozygous 1/3 alleles or homozygous 1/1 or 3/3 alleles in the 5' flanking region of the insulin gene had similar plasma insulin and C-peptide concentrations and similar estimates of beta-cell function. This suggests that the large DNA insert (Class 3 allele) near the insulin gene does not directly affect insulin secretion. The association of polymorphisms with Type 2 diabetes may be due to linkage disequilibrium with other disease-related alleles.

Adult↗