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Biomedical subjects

L Sestoft

Publications and source records attributed to L Sestoft.

At least 55 records · Page 3Linked to original sources
PubMed1983

Response of pancreatic polypeptide to hypoglycaemia in insulin-dependent diabetics with and without residual beta-cell function.

To investigate a possible association between the beta-cells and the cells secreting pancreatic polypeptide (PP), the response of PP to insulin-induced hypoglycaemia was investigated in seven insulin-dependent diabetics with and seven without residual beta-cell function, all without signs of autonomic neuropathy. The mean concentrations of PP was significantly greater from 15 to 60 min after symptoms of hypoglycaemia in patients with residual beta-cell function than in patients without (P less than 0.05) despite similar blood glucose concentrations in the two groups. Also the total integrated areas beneath the response curves as well as the incremental integrated areas were significantly greater in patients with beta-cell function (216 +/- 36 pmol/l x min and 188 +/- 34 pmol/l x min, respectively) than in patients without beta-cell function (125 +/- 26 pmol/l x min and 102 +/- 26 pmol/l x min) (P less than 0.05 for both). The mean maximal concentrations of adrenaline (1.53 +/- 0.28 ng/ml v. 1.29 +/- 0.12 ng/ml) and noradrenaline (0.56 +/- 0.16 ng/ml v. 0.45 +/- 0.04 ng/ml) were not statistically different in the two groups. No well established explanation for an association between residual insulin secretion and capacity for PP-response to hypoglycaemia in type 1 diabetics exists.

Adult↗
PubMed1983

Concentrative uptake of alanine in hepatocytes from fed and fasted rats.

The transport of alanine across the liver cell membrane was studied in hepatocytes isolated from fed and 48-h-fasted rats. Aminooxyacetate was used to render alanine nonmetabolizable. The steady-state intracellular-to-extracellular distribution ratio of alanine was maximal at extracellular concentrations below 0.5 mM and was increased from about 10 to about 20 by fasting. This increase was the net effect of a two- to threefold increase in the alanine influx and about a 50% increase in the rate constant of alanine efflux. The results suggest that alanine efflux occurred partly via the transport system mediating Na+-dependent alanine influx and partly by another pathway. The transmembrane Na+ electrochemical gradient remained unchanged by fasting and could apparently account for a maximal distribution ratio of alanine well above 20. In both nutritional states, the simplest kinetic model adequately describing the alanine influx implicated one saturable component besides a passive component. The apparent Vmax of the former was doubled by fasting while the apparent Km was insignificantly decreased. At low extracellular alanine concentrations, the rate of alanine consumption (aminooxyacetate absent) was only 40% of the alanine influx in the fed state but was increased at least fivefold by fasting and thereby balanced with the increased alanine influx. These results suggest a rate limitation at the transport level in the fasted state.

Alanine↗
PubMed1983

Diminished immunoreactive gastric inhibitory polypeptide response to a meal in newly diagnosed type I (insulin-dependent) diabetics.

The release of immunoreactive gastric inhibitory polypeptide (IR-GIP) in response to a standard meal was examined in 10 normal subjects and 15 type I (insulin-dependent) diabetics 7 days (test I), 14 days (test II), and 3 months (test III) after time of diagnosis. During all three tests, the diabetics had significantly lower plasma IR-GIP concentrations than the controls from 15-90 min after the standard meal. The IR-GIP response in the diabetics measured as the integrated area under the response curve corresponded to 70% of that of normal subjects. beta-cell function evaluated from the C-peptide response to the meal increased significantly from test I to test III whereas the IR-GIP response was similar during all three tests. As GIP is known to potentiate glucose-induced insulin secretion and possibly the biosynthesis of insulin, the low IR-GIP responses in subjects with type I diabetes may significantly influence insulin levels and hyperglycemia.

Adolescent↗
PubMed1982

Acid-base balance in diabetic ketoacidosis.

Acid-base balance during development of diabetic ketoacidosis was reappraised on the basis of old studies on urinary excretion of ions. Circulatory collapse with impaired urinary excretion of acids is a prominent feature of the late phase of diabetic ketoacidosis, in which pathophysiological measurements are difficult to make. To elucidate the balance between hepatic uptake of carboxylic acids (free fatty acids and lactate plus pyruvate) and hepatic release of carboxylic acids (ketone bodies and lactate plus pyruvate) during the late phase of diabetic ketoacidosis, perfused livers from normal and streptozotocine-diabetic rats, fasted for 48 h, were subjected to high perfusate glucose concentrations, low perfusate pH and low perfusate flow rates. Provided that flow was kept normal, there was always a net uptake of carboxylic acids. At normal flow, a low pH and a high glucose concentration in the perfusate did not affect the hepatic uptake of lactate plus pyruvate or the flux of carbon from lactate to glucose. Reduction of the perfusate flow rate by two-thirds invariably turned the liver into a state of net carboxylic acid production. The net uptake of lactate plus pyruvate was greatly reduced, mainly due to initiation of a glycolytic flux.

Acid-Base Equilibrium↗
PubMed1982

Hormonal, metabolic and cardiovascular responses to hypoglycaemia in Type 1 (insulin-dependent) diabetes with and without residual B cell function.

Hormonal, metabolic and cardiovascular responses to insulin induced hypoglycaemia were investigated in seven Type 1 (insulin-dependent) diabetic patients with residual B cell function, eight Type 1 diabetic patients without B cell function and six healthy subjects. No differences were found between the diabetic groups regarding nadir of glucose and rate of recovery to normoglycaemia. The patients with residual B cell function had a glucagon response to hypoglycaemia which was close to that of normal subjects. In patients without B cell function, the glucagon response to hypoglycaemia was present, albeit significantly smaller than in the patients with preserved B cell function (0.025 ng/ml, range 0.007-0.042 versus 0.054 ng/ml, range 0.029-0.087). The group without B cell function had signs of an exaggerated rate of lipolysis and ketogenesis compared with the patients with B cell function and the normal subjects.

Adult↗
PubMed1982

Hypothalamic-pituitary-adrenocortical function in chronic alcoholism.

Hypothalamic-pituitary-adrenocortical (HPA) function was assessed during normal daily work and family life in fifteen male brewery workers with a daily alcohol intake of 100 g or more for at least 10 years. Free urinary cortisol was determined during three baseline days and for 3 days during administration of dexamethasone 0.5 mg 6-hourly. All subjects had normal basal urinary cortisol excretion and all except one suppressed normally upon dexamethasone. Four subjects had Cushingoid-like moon face and two of these also had buffalo hump. There was no correlation between free urinary cortisol excretion or dexamethasone suppression and the Cushingoid stigmata. These results suggest that chronic alcohol intake per se does not influence HPA-function.

Adult↗
PubMed1982

Pathophysiology of metabolic acidosis: effect of low pH on the hepatic uptake of lactate, pyruvate and alanine.

The uptake of lactate, pyruvate and alanine in perfused rat liver was investigated under normal perfusion conditions (pH 7.4, PCO2 40 mmHg) and under conditions mimicking partially compensated metabolic acidosis (pH 6.9, PCO2 20 mmHg). At 1 mM lactate as well as 10 mM lactate in the medium a lowering of pH from 7.4 to 6.9 did not affect the lactate plus pyruvate uptake. A significant effect of the low pH was seen on pyruvate uptake which at 1 mM lactate was increased from 0.027 +/- 0.008(4) mumol/min per g liver at normal pH to 0.084 +/- 0.013(4) at low pH. At 10 mM lactate the liver produced pyruvate, but the production was significantly reduced by a lowering of the pH, being 0.45 +/- 0.13(8) mumol/min per g liver at pH 7.4 and 0.22 +/- 0.06(4) at pH 6.9. THe counterbalancing changes in lactate metabolism were too small to attain statistical significance. The stimulation of gluconeogenesis by an increase in FFA from 0 to 1 mM in the medium was unaffected by pH. Alanine uptake was decreased from 0.48 +/- 0.05(6) to 0.39 +/- 0.07(3) by lowering the pH from 7.4 to 6.9. We conclude that metabolic acidosis does not in itself inhibit the capacity of the perfused rat liver to remove lactate and pyruvate from the blood. If the same is true in man, no beneficial effect of bicarbonate treatment on lactate clearance in patients with lactic acidosis should be expected.

Acidosis↗
PubMed1982

Subcutaneous blood flow during insulin-induced hypoglycaemia: studies in juvenile diabetics with and without autonomic neuropathy and in normal subjects.

Subcutaneous blood flow was measured preceding insulin-induced hypoglycaemia, at the onset of hypoglycaemic symptoms and 2 h later in juvenile diabetics with and without autonomic neuropathy and in normal males. In all groups subcutaneous blood flow decreased at the onset of hypoglycaemic symptoms compared with pre-hypoglycaemic flow. Two hours after onset of hypoglycaemic symptoms, subcutaneous blood flow was still significantly decreased compared with pre-hypoglycaemic flow. In normal subjects local nerve blockade had no effect on blood flow changes during hypoglycaemia, whereas local alpha-receptor blockade abolished the vasoconstrictor response. We suggest that circulating catecholamines stimulating vascular alpha-receptors are probably responsible for flow reduction in the subcutaneous tissue during hypoglycaemia.

Adult↗
PubMed1982

No response of pancreatic hormones to hypoglycemia in diabetic autonomic neuropathy.

The responses of pancreatic hormones (i.e. glucagon, pancreatic polypeptide, and somatostatin) to insulin-induced hypoglycemia were investigated in 18 insulin-dependent diabetics without residual beta-cell function and in 6 normal subjects. Nine of the diabetics had autonomic neuropathy, and 9 had no neuropathy. After hypoglycemia, no significant increase in any of the 3 pancreatic hormones was found in the diabetics with autonomic neuropathy, whereas significant increments were found in the diabetics without neuropathy and in the normal subjects. These results suggest that autonomic nervous activity is of major importance for pancreatic hormone release during hypoglycemia in man.

Adult↗
PubMed1981

Hypersecretion of proinsulin in thyrotoxicosis.

The plasma insulin, C-peptide and proinsulin concentrations were investigated in thyrotoxic patients and in normal controls after an overnight fast, during a 36 h fasting period, an intravenous glucose tolerance test and an oral glucose tolerance test. The main finding was a significantly raised concentration of proinsulin in plasma of patients with thyrotoxicosis. After an overnight fast the plasma proinsulin was 0.048 +/- 0.005 pmol/ml in 15 thyrotoxic patients compared with 0.023 +/- 0.012 pmol/ml in 15 euthyroid controls. A twofold rise of plasma proinsulin concentration was also found in thyrotoxic patients during a prolonged fast, and during intravenous and oral glucose tolerance tests. The immunoreactivity of proinsulin in the insulin radioimmunoassay gave rise to slightly elevated concentrations of immunoreactive insulin in thyrotoxic patients in all the conditions investigated. When insulin values were corrected for proinsulin crossreactivity, they were similar in euthyroid controls and thyrotoxic patients. The concentration of plasma C-peptide was not significantly altered in thyrotoxic patients during intravenous and oral glucose tolerance tests.

Adult↗
PubMed1981

The blood-retinal barrier permeability in diabetic patients.

By the of aid an extended corpus vitreum fluorophotometric technique, the blood-retinal barrier permeability for fluorescein was studied in diabetologically well characterized patients with insulin dependent diabetes mellitus. The method, which involves simultaneous determination of the fluorescein concentration in corpus vitreum and plasma, is described and discussed. A clear correlation was found between the degree of retinopathy and permeability (P). Patients with normal visus, ophthalmoscophy, fundus photo and fluorescence angiography exhibited P-values of 1.10(-7) cm . sec-1. This was similar to P-values found in normal volunteers. Simplex retinopathy without macular oedema showed values of 2.5 . 10(-7) cm . sec-1 while simplex retinopathy with macular oedema showed P-values of 10 . 10(-7) cm . sec-1.

Capillary Permeability↗
PubMed1980

Thyroid hormone-induced changes in gluconeogenesis and ketogenesis in perfused rat liver.

The regulation of ketogenesis and gluconeogenesis was studied in isolated, perfused livers from hyper- and euthyroid rats. Experimental conditions were varied with respect to lactate and fatty acid concentration in the perfusion medium and with respect to the nutritional state of the rats. 1. The rate of uptake of oleate in perfused livers was independent of the thyroid and nutritional states of the animals. 2. In livers from 48-h-fasted rats no difference was found in rates of ketogenesis between the euthyroid and hyperthyroid livers except when 10 mM lactate was present in the perfusate. In recently fed rats the rates of ketogenesis from oleate (1 mM) and endogenous substrates were low in euthyroid livers (0.45 and 0.05 mumol/min per g liver, respectively), while these rates in hyperthyroid livers were (1.333 and 0.136 mumol/min per g liver, respectively). With octanoate as substrate, high rates of ketogenesis were found in recently fed livers from both euthyroid and hyperthyroid rats (1.573 and 1.717 mumol/min per g liver, respectively). 3. Without oleate in the perfusion medium the rate of gluconeogenesis from low (1 mM) lactate concentrations in livers from 48 h-fasted-rats was slightly increased in the hyperthyroid state (0.548 mumol/min per g liver) compared to the euthyroid state (0.408 mumol/min per g liver). When lactate concentration in the perfusion medium was raised to 10 mM the rate of gluconeogenesis was increased 4-fold in the hyperthyroid livers (1.800 mumol/min per g liver) but only 20% in the euthyroid livers (0.490 mumol/min per g liver). The presence of oleate (1 mM) had no effect on the rate of gluconeogenesis from low lactate concentrations in livers form 48-h-fasted animals of either thyroid state. At 10 mM lactate the inclusion of oleate caused a pronounced stimulation of gluconeogenesis in euthyroid livers (from 0.490 to 1.766 mumol/min per g liver) but not in hyperthyroid livers (from 1.800 to 1.973 mumol/min per g liver) so that the difference in the rate of gluconeogenesis between the two thyroid states disappeared. 4. The content of endogenous substrates was measured in liver biopsies taken before perfusion. The glycogen concentration was independent of the thyroid state in 48-h fasted animals. The triglyceride content was independent of the thyroid state in recently fed animals. In recently fed animals the glycogen content was reduced by 90% in hyperthyroid animals, and in 48-h-fasted animals the triglyceride content was reduced by 50% in hyperthyroid animals. 5. The energy cost of gluconeogenesis from lactate appeared to be independent of the thyroid state.

Animals↗