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Biomedical subjects

L Sestoft

Publications and source records attributed to L Sestoft.

At least 73 records · Page 4Linked to original sources

Metabolic responses to hypoglycemia in juvenile diabetics.

Glucagon and metabolic responses to insulin-induced hypoglycemia were studied in seven juvenile diabetics, age 31 +/- 2 years (mean and S.E.M.), duration of diabetes 17 +/- 3 years, with diabetic autonomic neuropathy (decreased beat-to-beat variation in heart rate during hyperventilation and/or orthostatic hypotension) and in seven control patients of similar age and duration of diabetes with out neuropathy. Before the hypoglycaemic episode, normoglycemia had been maintained for at least 10 hours. Following hypoglycemia, a slight but significant and similar increase in plasma glucagon was found in both patient groups. Metabolic responses to hypoglycemia were also similar in the two patient groups. In conclusion, diabetic autonomic neuropathy has no effect on glucagon and metabolic responses to hypoglycemia in juvenile, insulin-treated diabetics.

Adult↗

Metabolic aspects of the calorigenic effect of thyroid hormone in mammals.

The increased BMR in hyperthyroidism may be accounted for by the use of chemical energy for metabolic processes and work. Major contributors are the heart work and futile cycling of FFA into triglyceride in adipose tissue, whereas gluconeogenesis in liver and the maintenance of sodium and potassium concentration gradients across the plasma membranes are unlikely to play any significant role. Information on the use of energy for protein turnover and urea production is lacking. The rate of oxygen uptake is not increased in the brain, spleen and testis. The main metabolic fuel seems to be free fatty acid. The mechanism which enables the hyperthyroid tissue to maintain normal concentrations of ATP, ADP and inorganic phosphate, (Pi) despite an increased turnover of energy-rich phosphates, is not fully elucidated. However, ultimately the increased rate of oxygen uptake in hyperthyroidism seems to rely upon an increased capacity for the transport of cytosolic ADP and Pi into mitochondria. The transport capacity is increased by an increased area of the mitochondrial membrane per g tissue and by a change in the kinetics of translocation of substrates for oxidative phosphorylation. Other transport processes across the mitochondrial membrane are also changed by hyperthyroidism, e.g. long chain fatty acid transport via carnitine acyl transferase, and oxaloacetate transport via substrate shuttles.

Adenosine Diphosphate↗

Impaired response of pancreatic polypeptide to hypoglycaemia: an early sign of autonomic neuropathy in diabetics.

The pancreatic polypeptide (PP) response to insulin-induced hypoglycaemia was studied in 18 juvenile diabetics and was calculated as the difference between the prestimulatory PP concentration and the maximal concentration measured. The response was severely impaired in patients with autonomic neuropathy (mean +/- SE of mean 22 +/- 12 pmol/l) as compared with patients without neuropathy (252 +/- 51 pmol/l). Patients whose diabetes was of only a few years' duration showed a normal PP response to hypoglycaemia, and the response diminished significantly with increasing duration of diabetes. The decreased PP response to hypoglycaemia was significantly correlated with an increased threshold of the sense of vibration, (rs = 0.86). These results suggest that impaired, secretion of PP may serve as an early sign of autonomic neuropathy in diabetes.

Adult↗

Development of ketonemia in fasting patients with hyperthyroidism.

Concentrations of ketone bodies, free fatty acids, glycerol, lactate, glucose, insulin, glucagon and cortisol were determined 6-hourly during 36 hours of fasting in 4 hyperthyroid patients and in 4 euthyroid controls. The concentrations of ketone bodies were elevated in hyperthyroid patients from the beginning and increased during fasting more rapidly and to higher values as compared to the controls. After 6 hours of fasting the blood ketone concentrations were 1.1--1.8 mM in hyperthyroid patients and 0.3--0.6 mM in the controls. After 36 hours the concentrations had increased to about 3.5 mM and 1.4 mM in hyperthyroid and control subjects, respectively. The concentrations of free fatty acids were identical in the groups compared postprandially, but increased significantly more in the hyperthyroid patients than in the controls during fasting. The glycerol concentration was higher in the hyperthyroid group throughout the observation period. The concentrations of insulin were slightly higher in the hyperthyroid group than in the control, whereas the concentrations of the "ketogenic" hormones, glucagon and cortisol were identical in the compared groups. It is concluded that hyperthyroidism leads to an increased tendency to ketosis, that is partly explained by increased concentrations of free fatty acids and that might also involve a direct action of long term thyroid hormone excess on enzyme activities (e.g. carnitine acyltransferase in liver).

Adult↗

Determination of unidirectional fluxes of phosphate across plasma membrane in isolated perfused rat liver.

In livers labeled with 32P by intraperitoneal injection 18 h before perfusion the unidirectional efflux of inorganic phosphate (Pi) was a linear function of the concentration of Pi in the intracellular exchangeable pool of Pi (range, 0--1 mumol/g liver). Calculations of the efflux were based on determination of the specific radioactivity of Pi in the intracellular exchangeable pool of Pi by a new method. Zero efflux was found at biopsy concentrations of Pi of about 1.8 mumol/g liver. The influx of Pi was calculated from the efflux and the net uptake of Pi; it was found to be related to the extracellular concentration of Pi in a fashion that was approximately linear. An increase in the concentration of Pi in the input medium gave rise to an increased influx and, with a time delay, also to a gradually increasing efflux. The increased efflux could be explained as a consequence of an increased intracellular concentration of exchangeable Pi.

Animals↗