Evidence that the presence of arginine can lead to overestimation of glucagon levels measured by radioimmunoassay.
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Biomedical subjects
Publications and source records attributed to J H Scarpello.
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Colour vision function was assessed in 38 non-complicated type 1 diabetic patients in whom fluorescein angiography was normal, and was compared with that in 36 age-matched, non-diabetic controls. All of the patients were healthy and none were taking medication except insulin. The eye examination, which was normal in every patient, included the Ishihara and City University tests, measurement of Snellen acuity, slit-lamp examination, tonometry, and fundal photography as well as fluorescein angiography. Colour discrimination ability was measured with the Farnsworth-Munsell 100-hue test. Mean (SE) 100-hue test error score for the diabetic group was 86.8 (8.1) compared with 28.2 (3.3) for controls, p<<0.001. There was no relation between colour vision abnormalities and diabetes duration (r = 0, p>0.05), blood glucose at the time the colour tests were performed (r = 0.4, p > 0.05), most recent glycated haemoglobin result (r = 0.3, p>0.05), or the mean of all previous glycated haemoglobin results (r = 0, p>0.05). It is concluded that colour discrimination may be abnormal in uncomplicated type 1 diabetic patients before the onset of retinopathy, and that colour discrimination losses in diabetes may not be of vascular aetiology.
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1. In rat isolated islets of Langerhans the selective beta 2-adrenoceptor agonist, clenbuterol (1 to 20 microM), significantly increased the level of adenosine 3':5'-cyclic monophosphate (cyclic AMP) within 2 min of incubation. 2. The cyclic AMP response to clenbuterol was inhibited in the presence of the selective beta 2 adrenoceptor antagonist, ICI 118551 (0.1 or 10 microM) but remained unchanged when the beta 1-antagonist, atenolol (0.1 microM) was administered. 3. Despite causing an elevation in cyclic AMP, clenbuterol (up to 20 microM) failed to influence insulin secretion at any glucose concentration tested, even in the presence of a phosphodiesterase inhibitor. 4. By contrast, clenbuterol elicited a dose-dependent rise in the rate of glucagon secretion; the maximal agonist-induced increase in secretion was two fold, a response equivalent to that observed with 20 mM L-arginine. 5. ICI 118551 significantly inhibited the rise in glucagon secretion induced by clenbuterol (up to 20 microM). 6. The results indicate that the rat islet A cell population is equipped with functional beta 2-adrenoceptors which influence glucagon secretion via the second messenger cyclic AMP, but that the B cells are deficient in functional beta-receptors.
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The selective beta 2-adrenergic agonist clenbuterol was ineffective as a stimulus for insulin secretion when isolated rat pancreatic islets were incubated with glucose at concentrations between 4 and 20 mM. Inclusion of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine led to potentiation of glucose-induced insulin secretion, but did not facilitate stimulation by clenbuterol. Furthermore, maintenance of isolated rat islets for up to 3 days in tissue culture also failed to result in the appearance of a secretory response to beta-agonists. By contrast, clenbuterol induced a dose-dependent increase in insulin release from isolated human islets incubated with 20 mM glucose. Clenbuterol did not increase the basal rate of insulin secretion (4 mM glucose) in human islets. Under perifusion conditions, the secretory response of human islets to clenbuterol was rapid, of similar magnitude to that seen under static incubation conditions and could be sustained for at least 30 min. The increase in insulin secretion induced by clenbuterol was inhibited by propranolol, indicating that the response was mediated by activation of beta-receptors. In support of this, a similar enhancement of glucose-induced insulin secretion was elicited by a different beta 2-agonist, salbutamol, in human islets. The results indicate that the B cells of isolated rat islets are unresponsive to beta-agonists, whereas those of human islets are equipped with functional beta-receptors which can directly influence the rate of insulin secretion.
Reducing the rate of glucose absorption is a useful approach to the treatment of noninsulin-dependent diabetes mellitus (NIDDM). Intestinal absorption of glucose and amino acids is known to be increased in diabetes in laboratory animals but has not been systematically studied in human NIDDM subjects. In this study the intestinal absorption of glucose and glycine was measured during steady-state perfusion of the jejunum in 10 NIDDM subjects and in 11 healthy volunteers. Absorption rates were linearly related to solute load for both glucose and glycine. Over the range of solute concentrations, absorption rates of glucose (F = 4.38, p less than 0.05) and glycine (F = 7.07, p less than 0.02) were slightly reduced in diabetic subjects. The reduction in absorption rates may be accounted for by differences in age and diet between the groups. It is concluded that glucose and amino acid absorption is not increased in human NIDDM.
Six noninsulin-dependent diabetic subjects received meals containing 25 g carbohydrate either as potato or as spaghetti. The meals were repeated with the addition of 25 g protein and with 25 g protein and 25 g fat. Blood glucose and insulin responses were measured for 4 h after the test meal. When carbohydrate was given alone, the blood glucose and serum insulin increments were higher for the potato meal. The addition of protein increased the insulin responses to both carbohydrates and slightly reduced the glycemic response to mashed potato (F = 2.04, p less than 0.05). The further addition of fat reduced the glycemic response to mashed potato (F = 14.63, p less than 0.001) without any change in the blood glucose response to spaghetti (F = 0.94, NS). The different responses to coingestion of protein and fat reduced the difference between the glycemic responses to the two carbohydrates.
The effect of guar on the absorption of the calcium isotope 45Ca was measured in six normal subjects. Values for the delay before the initial rise of radioactivity in plasma (delta t) and the initial fractional absorption rate (alpha) were derived using a non-linear curve-fitting computer programme. Guar significantly reduced the fraction of 45Ca absorbed between 15 and 120 min. Guar increased the delay before the initial rise of radioactivity in plasma and reduced the initial fractional absorption rate. The results show that a dietary fibre which does not bind calcium in vitro reduces the rate of calcium absorption in man.
The effect of guar on the plasma glycine response to a glycine drink was measured in six normal subjects. Guar reduced the increment in plasma glycine over the first 60 min and also reduced the total integrated plasma glycine response. The effect of guar on the peripheral blood glucose, insulin, C-peptide and glucagon responses following jejunal amino acid or glucose perfusion was measured in nine normal subjects. Guar reduced the blood glucose, insulin and C-peptide responses to the glucose perfusion and reduced the insulin and C-peptide responses to the amino acid perfusion. The addition of guar did not alter C-peptide:insulin ratios following either glucose or amino acid administration. It is concluded that guar reduces the rate of amino acid absorption and of amino acid-stimulated insulin release. Modulation of intestinal mechanisms is sufficient to mediate the latter effect. The reduction in peripheral blood insulin levels caused by guar is not associated with a change in hepatic insulin extraction.
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A 57-year-old woman presented with symptoms which were cured by the removal of an insulinoma. The case was atypical in that symptomatic hypoglycaemia occurred only after meals or glucose administration but never during fasting, and thus if plasma insulin activity had not been measured an incorrect diagnosis of reactive hypoglycaemia might have been made on the basis of symptoms and oral glucose-tolerance test. Reactive hypoglycaemia resulted from an increased rate of glucose assimilation and possibly also from a decreased rate of gluconeogenesis due to the immense insulin secretion provoked by glucose or food. The findings suggest that a diagnosis of hypoglycaemia should not be made until the possibility of an insulinoma has been excluded by measurement of plasma insulin activity during a period of hypoglycaemia.
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The (14)C-glycocholic acid test ((14)C-GCA) has been assessed in 27 patients who have had resection of the ileum and colon for Crohn's disease and in 19 patients with unoperated stable Crohn's disease. The incidence of increased breath output of (14)CO(2) and faecal output of (14)C was significantly greater in operated patients. Half the unoperated patients had normal results and, of the others, a modest increase in faecal (14)C was the usual finding. There was no correlation between the (14)C-GCA test, the Schilling test, and the extent and severity of the radiological signs in the unoperated patients. Metronidazole therapy was poorly tolerated and had little or no influence on symptoms but did decrease the excretion of (14)CO(2) in the breath when the (14)C-GCA test was repeated. Cholestyramine therapy was beneficial in the majority of resected patients with diarrhoea and an increased faecal (14)C excretion and, on repeat testing, there was a significant increase in the output of breath (14)CO(2). The beneficial effect was less marked in the unoperated patients and the breath (14)CO(2) output remained normal in those retested. Interruption of the enterohepatic circulation of bile acids did not seem to make an important contribution to the symptoms of patients with stable unoperated (and uncomplicated) Crohn's disease, even when the ileum was extensively involved.
The (14)C-glycocholate test, including the measurement of marker corrected faecal (14)C, has been assessed in the following groups of subjects: normal controls (18), patients with diarrhoea not attributable to altered bile acid metabolism (21), patients with diverticula of the small intestine (12), patients with previous resection of ileum and often proximal colon (34), and established ileostomists (10). Patients with diverticular disease had increased breath (14)CO(2) excretion, but normal faecal excretion of (14)C, and this test was more frequently abnormal than the Schilling test. Ileostomists excreted increased amounts of faecal (14)C, even when the ileum was intact and apparently normal. The pattern after resection was complex. Breath (14)C output was normal if the ileal resection was less than 25 cm in length, although some of these patients had increased faecal (14)C excretion if, in addition, at least 15 cm of proximal colon had been resected or by-passed. Longer ileal resections were associated with increased breath and/or faecal (14)C excretion, depending in part on the length of colon resected or by-passed and the 24 hour faecal volume. Fewer than half these patients had both increased breath and faecal excretion of isotope and faecal (14)C alone was occasionally normal with an ileal resection of 50 cm of more. The (14)C-glycocholate test was more frequently abnormal than the Schilling test in this group. The use of faecal marker correction had only a minor impact on the results. These data suggest that, in patients with ileal resection, faecal (14)C, like faecal weight, is determined by the extent of colonic resection as well as by the amount of ileum resected.
A case of severe diarrhoea and steatorrhoea following chemotherapy and abdominal irradiation for lymphosarcoma, is described. Investigations demonstrated bile acid malabsorption, and treatment with cholesytramine and a low fat diet was successful. A questionnaire was sent to thirty-two subjects who had undergone similar treatment for similar pathology and failed to demonstrate any sustained alteration of bowel function. Additionally, nine of these subjects underwent a 14C-glycocholic acid test and no evidence of interruption of the enterohepatic circulation of bile acids was found.