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Biomedical subjects

J A Matthews

Publications and source records attributed to J A Matthews.

35 records · Page 2Linked to original sources
PubMed1983

The bioavailability of circulating antibody-bound insulin following insulin withdrawal in Type 1 (insulin-dependent) diabetes.

Insulin withdrawal studies were performed in 12 Type 1 (insulin-dependent) C-peptide negative diabetic patients with low to moderate insulin antibody levels, to assess the biological availability of antibody-bound insulin and its clinical significance. There was a highly significant correlation between the extent to which the free insulin concentration was maintained during the period of insulin withdrawal and both the level of insulin-binding by serum and the total insulin concentration at the start of the study. During insulin withdrawal, the patients who best maintained their circulating free insulin levels showed the smallest increases in blood glucose and 3-hydroxybutyrate concentrations. We conclude that antibody-bound insulin is available for physiological action, and that in those individuals with moderate antibody concentrations it is capable, in the fasting state, of maintaining free insulin levels. In these circumstances insulin antibodies are behaving as simple carrier proteins.

3-Hydroxybutyric Acid↗
PubMed1983

Comparison of peripheral glucose uptake after oral glucose loading and a mixed meal.

Forearm glucose uptake (FGU) and other metabolic responses were studied in six normal men for three hours after a 75-g oral glucose load and a mixed meal containing 75 g carbohydrate. After the meal the rise in arterial glucose levels was considerably less than that following the oral glucose load but the overall insulin responses from 0 to 180 minutes were not statistically different. Although the initial rise in FGU was more gradual after the meal, the subsequent elevation was more sustained and, at the termination of the study, exceeded significantly that seen after the oral glucose load. The rise in GIP levels during the first hour was similar after the meal and the oral glucose load, but thereafter concentrations following the oral glucose load fell while those after the meal continued to rise. When the incremental area (delta) is used as the index of response, the results show that while the glucose response (delta G) after the meal (19.1 +/- 5.3 units) was only 26% of that after oral glucose loading (72.7 +/- 7.0 units), the corresponding increase in FGU (delta FGU) reached 62% (55.0 +/- 12.8 units after the meal, 89.2 +/- 20.0 units after the oral glucose load). Thus, the increase in peripheral glucose uptake relative to the glycemic response (delta FGU/delta G) was significantly greater after the meal than following the oral glucose load alone (P less than 0.05). In conclusion, relative to the rise in arterial glucose levels, peripheral glucose uptake is greater after a meal than after glucose loading with an equivalent carbohydrate challenge. Furthermore, the present data support previous studies emphasizing the failure of GIP alone to explain the entero insular axis.

Administration, Oral↗
PubMed1983

The physiological effects of insulin-induced hypoglycaemia in man: responses at differing levels of blood glucose.

The aim of this study was to describe hormonal, cardiovascular and thermoregulatory responses to insulin-induced hypoglycaemia of differing levels of severity. Five normal male volunteers were rendered hypoglycaemic at intervals of 1 week by intravenous infusions of 3, 4 or 6 units of insulin/h, or by intravenous injection of 0.15 unit/kg body weight. Plasma glucose reached nadir values of 2.08 +/- 0.10, 1.82 +/- 0.21, 1.24 +/- 0.08 and 0.92 +/- 0.06 mmol/l (means +/- SEM) in the four experiments. Non-esterified fatty acid levels fell equally in all experiments but recovery was more rapid with severe hypoglycaemia. In contrast the rate of recovery of plasma glucose was slower with deeper hypoglycaemia and this appeared unrelated to the counter-regulatory response. Plasma glucagon, adrenaline and prolactin levels increased in proportion to the severity of hypoglycaemia, but peak concentrations of cortisol, growth hormone (somatotropin) and noradrenaline did not vary, suggesting that moderate hypoglycaemia had elicited maximal responses. When the areas under the curves were calculated, the cortisol responses were greater for the 6 units infusion and bolus injection than for the other infusions, and the growth hormone responses were similar for all three infusions but significantly greater with the bolus injection. Increases in heart rate and systolic blood pressure were related to the severity of hypoglycaemia, but changes in diastolic blood pressure and peripheral vascular resistance (assessed from calf and from hand blood flow) were not. Central temperature fell by 0.13 +/- 0.06 degrees C, 0.30 +/- 0.10 degrees C, 0.65 +/- 0.14 degrees C and 1.15 +/- 0.30 degrees C (means +/- SEM) in the four experiments, and the fall in skin temperature had a similar gradation. Many physiological responses to hypoglycaemia are not 'all-or-none', but vary according to the intensity of stimulus; some are already maximal at mild degrees of hypoglycaemia. Other changes are more complex, reflecting an interplay between opposing endocrine and neural responses.

Adult↗
PubMed1983

Peripheral glucose uptake in young men with myocardial infarction.

Forearm glucose uptake (FGU) was studied during 100 g oral glucose tolerance tests (GTT) in nonobese, nondiabetic men who had suffered a myocardial infarction (MI) at or before the age of 40, and the results compared with the response in age-matched normal men. In the MI group the rise in both glucose and insulin concentrations after glucose loading was similar to that in normal subjects, although in the former, peak levels tended to be slightly higher. Concomitant FGU, however, was significantly greater in the MI group than in control subjects in the period 0-90 min and in the test as a whole (0-180 min). The results show that at least in some nondiabetics suffering MI at an early age hyperinsulinism is not a feature and peripheral tissue sensitivity is increased.

Adult↗
PubMed1982

Genetic and immunologic factors in microvascular disease in type I insulin-dependent diabetes.

A detailed study of 133 subjects with insulin-dependent (type I) diabetes with severe microvascular disease has failed to substantiate the hypothesis that HLA factors influence the predisposition to this type of complication. A significant association between proliferative retinopathy and raised levels of circulating immune complexes was found. The distribution of insulin-binding levels in serum was similar to that in patients without complications. There was no correlation between insulin binding and the presence of immune complexes and no evidence was found that these complexes contained anti-insulin, anti-nuclear, or organ-specific antibodies. The distribution of insulin-binding levels in these subjects with diabetes of long duration was similar to that observed in 270 subjects with juvenile-onset short-duration type I diabetes. When the data were combined, significant associations between HLA-B8 and low/absent insulin binding levels were observed. HLA-BW62 was not associated with either high or low insulin-binding capacity. It is concluded that HLA genetic factors, insulin-binding capacity, and autoimmunity are unrelated to the pathogenesis of microvascular disease. Raised levels of circulating immune complexes may well be secondary to widespread tissue damage in diabetes of long duration.

Adult↗
PubMed1981

Molecular cloning and analysis of cDNA sequences derived from poly A+ RNA from barley endosperm: identification of B hordein related clones.

A collection of over 130 cDNA clones has been constructed in the bacterial plasmids pPH207 and pBR322 using as template the poly A+ RNA from membrane-bound polysomes of barley endosperm (cv. Sundance). Fifty four B hordein cDNA clones have been identified by cross-hybridization analysis and in vitro translation of plasmid-selected mRNAs. Hybridization of 11 of the B hordein cDNA clones to Northern blots of size-fractionated RNA indicated that the B hordein mRNA is ca. 1300 nucleotides long. One cDNA clone, pHvE-c16, has been partially sequenced and shown by comparison with C-terminal and other peptide sequences to be related to B1 hordein polypeptides. The results obtained from the analysis of the B hordein cDNA clones support the idea that the Hor 2 locus, which specifies the B hordeins, is complex and codes for a family of related mRNA species.

Base Sequence↗
PubMed1980

Decrease of antibodies to insulin, proinsulin and contaminating hormones after changing treatment from conventional beef to purified pork insulin.

The sera of 30 patients who had been treated with conventional beef insulin were tested for binding of insulin and other pancreatic hormones. All showed antibody binding of insulin, 29 binding of proinsulin, 29 binding of pancreatic polypeptide, two binding of glucagon but none of the sera bound vasoactive intestinal peptide or somatostatin. After changing therapy to highly purified pork insulin the binding capacity of sera for insulin and the other hormones was monitored for up to 35 months and a steady fall was found in nearly all cases. In eight of the patients conventional beef insulin treatment was resumed: in one month binding of insulin and of the other hormones increased back to the initial levels. In eighteen subjects who had only received highly purified pork insulin low levels of insulin binding were found with no binding of proinsulin or other hormones. The amounts of proinsulin and contaminating hormones in highly purified pork insulin are so low that they are not immunogenic; conventional beef insulin not only contains immunogenic amounts of proinsulin and the contaminating hormones pancreatic polypeptide and glucagon but also is more immunogenic than purified pork insulin.

Adolescent↗
PubMed1979

Factitious diabetes and antibody mediated resistance to beef insulin.

A case of factitious diabetes is reported. The patient gave herself insulin intermittently over a four year period. A high concentration of insulin binding antibody was found with the antibody showing much greater avidity towards beef than human insulin. There was resistance to intravenously administered beef insulin with low concentrations of free insulin and high concentrations of bound insulin. In contrast, in response to a glucose tolerance test, both the free insulin and C-peptide responses were normal as was glucose tolerance. The clinical difference in responsiveness to the human and beef insulins is well illustrated in vitro by insulin binding differences and is probably a function not only of different equilibrium constants of the antibody for human and beef insulins but also of different high affinity binding site concentrations.

Adult↗
PubMed1977

A gravimetric plethysmograph and its evaluation in clinical use.

A gravimetric plethysmograph, the technique of its use and its evaluation in vascular surgical practice are described. The instrument measures flow by the increase in leg weight (rather than volume) produced by an increase in blood content resulting from venous occlusion. The instrument was found to be convenient to use and satisfactory records were obtained in 88% of patients. Values for flow at rest and during reactive hyperaemia were clearly related to the presence of indications for surgical treatment and were similar to those reported by other workers. It is suggested that a peak hyperaemic flow of greater than 15 g 100 ml-1 min-1 may indicate that there are no indications for surgical treatment. The changes in hyperaemic flow values after treatment were clearly related to the symptomatic improvement resulting from it. It is concluded that the gravimetric plethysmograph is suitable for use in the assessment of patients with obliterative arterial disease of the legs.

Aged↗