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Biomedical subjects

L G Heding

Publications and source records attributed to L G Heding.

At least 19 recordsLinked to original sources
PubMed1991

Influence of portal delivery of insulin on intracellular glucose and lipid metabolism.

We have investigated whether portal delivery of insulin as a result of intrahepatic islet cell autografts would prevent the development of metabolic alterations. Seven pancreatectomized dogs received islet autografts transplanted into the liver through the portal vein (PD). One year after transplantation, their intravenous glucose tolerance and insulin responses were similar to age-matched control (C) dogs (n = 5). Also, normal triglyceride content in arterial smooth muscle and striated muscle was observed in the dogs with portal insulin delivery in contrast to the substantial increases we observed in pancreatectomized dogs (n = 7) with pancreatic autografts that drained into the systemic circulation (SD). In these dogs, the tissue samples were taken at the age of 3 to 4 years. Triglyceride content (mean +/- SEM) in the aorta was 4.9 +/- 1.2 versus 2.6 +/- 0.6 versus 20.7 +/- 8.0 mumol/g (P less than .01) in C, PD, and SD models, respectively. The corresponding values for triglyceride content in striated muscles were 29.1 +/- 1.2, 25.9 +/- 1.5, and 171.4 +/- 46.6 mumol/g (P less than .01). Glucose-6-phosphate dehydrogenase (G-6-PDH) and malic enzyme, key enzymes for lipid synthesis, were also normal in the PD model, in contrast to the fivefold increased activity of these enzymes in the SD model (P less than .01). The glycolytic enzymes, hexokinase (HK) and phosphofructokinase (PFK), were normal compared with the decreased values in the SD. These data indicate that it is possible to normalize glucose and lipid metabolism in arterial walls by portal delivery of insulin, following intrahepatic islet cell transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Changes in endogenous insulin secretion during childhood as expressed by plasma and urinary C-peptide.

Basal fasting values of plasma C-peptide (CP), plasma insulin and 24 h urine CP were determined in 224 normal non-obese subjects of both sexes ranging in age from 1 to 20 years. Analysis of the results by age, pubertal rating, sex and bone age (BA) during childhood showed that mean +/- SD plasma CP levels in both sexes rose from 0.07 +/- 0.08 pmol/ml at the age of 1-2 years to 0.21 +/- 0.11 pmol/ml at 8-10 years. Mean +/- SD plasma insulin levels in both sexes rose from 3.2 +/- 4.3 microU/ml at the age of 1-2 years to 5.9 +/- 4.5 microU/ml at 8-10 years. Mean +/- SD urine CP levels rose from 6.5 +/- 2.8 pmol/mg creatinine per 24 h at the age of 2-8 years to 7.7 +/- 3.5 pmol/mg creatinine per 24 h at 8-11 years in both sexes. During puberty, plasma and urine CP and plasma insulin levels rose further to peak at pubertal stage P3, the values in females being higher (CP = 0.32 +/- 0.06 pmol/ml) than those in males (CP = 0.22 +/- 0.06 pmol/ml) (P less than 0.005). Plasma insulin levels in females were 13.2 +/- 6.9 microU/ml and 6.4 +/- 3.1 microU/ml in males (P less than 0.05). Urine CP levels were 14.5 +/- 5.7 pmol/mg creatinine per 24 h and 10.8 +/- 5.4 pmol/mg creatinine per 24 h in females and males respectively (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Carbohydrate and lipid metabolism of skeletal muscle in type 2 diabetic patients.

Peripheral hyperinsulinaemia is the cause of metabolic changes that might contribute to the high incidence of macrovascular disease in patients with diabetes mellitus. In order to test this hypothesis muscle biopsies from 12 Type 2 diabetic patients and 14 age and sex matched non-diabetic patients, undergoing minor surgery, were obtained. The diabetic patients had significantly elevated fasting serum insulin (0.29 +/- 0.05 vs 0.06 +/- 0.03 nmol-1) and glucose (8.3 +/- 1.5 vs 4.6 +/- 0.5 mmol-1) and HbA1 levels (8.4 +/- 0.4 vs 5.0 +/- 0.2 per cent). The fasting and 2-h postprandial C-peptide levels were 0.99 +/- 0.25 vs 0.39 +/- 0.12 and 3.12 +/- 0.75 vs 1.09 +/- 0.34 nmol/l, respectively. The diabetic patients showed a marked elevation of triglyceride in the striated muscle biopsies compared to the non-diabetic controls (290 +/- 52 vs 48 +/- 6 mumol/g wet weight, p less than 0.001). Moreover, the activities of glucose-6-phosphate dehydrogenase (0.25 +/- 0.03 vs 0.13 +/- 0.01 U/g wet weight) and malic enzyme (0.15 +/- 0.01 vs 0.05 +/- 0.01 U/g wet weight), necessary for lipid synthesis, were significantly increased (both p less than 0.001) in the diabetic patients while the glycolytic enzymes, hexokinase (0.65 +/- 0.09 vs 1.82 +/- 0.11 U/g wet weight), pyruvate kinase (7.3 +/- 0.9 vs 13.2 +/- 0.9 U/g wet weight), phosphofructokinase (1.3 +/- 0.2 vs 2.6 +/- 0.2 U/g wet weight), and alpha-glycerophosphate dehydrogenase (7.3 +/- 0.5 vs 12.5 +/- 0.7 U/g wet weight) were decreased (all p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Development of insulin antibodies, metabolic control and B-cell function in newly diagnosed insulin dependent diabetic children treated with monocomponent human insulin or monocomponent porcine insulin.

One hundred and thirty eight patients participated in a two-year randomized, double-blind multicentre trial to compare monocomponent human insulin and porcine insulin in the treatment of newly diagnosed insulin dependent diabetic children with respect to development of insulin antibodies, metabolic control and B-cell function. There was no difference between the two patient groups throughout treatment either in the level of IgG insulin binding or the percentage of patients with insulin antibodies (IgG-insulin greater than 0.012 U/l). However, the estimated mean of log insulin binding values in the antibody positive patients alone was significantly lower (p less than 0.05) in the human insulin treated group at all times apart from 1 and 18 months (e.g., human insulin group at one and two years: 0.104 and 0.152 U/l, porcine insulin group at one and two years: 0.162 and 0.212 U/l). The insulin antibodies in both patient groups bound equivalent amounts of human and porcine insulin tracer. Metabolic control, insulin dosage and B-cell function in the two treatment groups were similar throughout the treatment period. It is concluded that in newly diagnosed insulin dependent diabetic children monocomponent human insulin is slightly less immunogenic than monocomponent porcine insulin, and equally effective in overall metabolic control.

Animals↗
PubMed1987

Intracellular metabolism in biopsies from the aorta in patients undergoing coronary bypass surgery.

Abnormal glucose and lipid metabolism in striated muscles and arterial wall has been demonstrated in 3 species: the pig, the dog, and human Type 2 diabetic patients, sharing the common feature of peripheral hyperinsulinaemia. In this study eighteen consecutive patients undergoing coronary bypass surgery and eight control patients were examined. Prior to surgery an oral glucose tolerance test showed that eleven out of eighteen patients had impaired glucose tolerance and significantly elevated fasting immune reactive insulin (IRI) and C-peptide concentrations. There was a statistically significant correlation between the 2 hour blood glucose value and the fasting plasma insulin level (R = 0.55, p less than 0.05). During the operation, aortic and muscle biopsies were taken. The eighteen patients undergoing coronary bypass surgery showed disturbances in glucose metabolism, i.e. decreased activity of glycolytic enzymes (hexokinase 0.30 +/- 0.06 versus 0.40 +/- 0.06 U/g, p less than 0.001, and phosphofructokinase 0.48 +/- 0.09 versus 0.61 +/- 0.07 U/g, p less than 0.01). Malic enzyme activity was increased in all patients (0.17 +/- 0.03 versus 0.06 +/- 0.02 U/g, p less than 0.001). Glucose-6-phosphate dehydrogenase was increased in the eleven patients with impaired glucose tolerance (0.55 +/- 0.10 versus 0.30 +/- 0.07, p less than 0.01) parallel to a significant increase in triglyceride content in the aortic wall (16.1 +/- 4.8 versus 3.7 +/- 3.2 mumol/g, p less than 0.01) as well as in the striated muscles (374 +/- 44 versus 48 +/- 6 mumol/g, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗
PubMed1979

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↗
PubMed1979

Metabolic studies in acute asthma before and after treatment.

We studied the metabolism and hormone profile of 9 patients with moderately severe acute asthma before treatment, and again 10 min after intravenous aminophylline (250 mg) or the selective beta-adrenergic stimulant hexoprenaline (5 microgram) intravenously. Compared with basal values in normal subjects the untreated asthmatics had statistically significant raised mean plasma pancreatic glucagon, free fatty acid (FFA) and glucose levels in the plasma and a significantly depressed mean plasma potassium level. Insulin, growth hormone, cortisol, thyrotropin and ketone body levels were normal. The only significant changes after therapy were a further fall in plasma potassium in the hexoprenaline-treated patients and a rise in the mean lactate concentration of the group as a whole. The clinical implications of these findings are briefly considered.

Acute Disease↗
PubMed1978

Hormonal profile, blood sugar control and HLA patterns in long-term insulin dependent diabetes with and without vascular disease.

Nineteen insulin dependent diabetics with onset at 30 years of age or less and duration of diabetes of greater than 25 years were divided into two groups on the basis of the presence or absence of clinically evident vascular disease. The patients without vascular disease were characterised by a later mean age of onset, lower fasting growth hormone concentration, and a lower frequency of the unusual HLA pattern B8 without A1 compared to the diabetics with vascular complications. The level of blood glucose control assessed over the last 15 years, insulin antibody titres, plasma glucagon levels and plasma cholesterol did not differ between the two groups. Residual beta cell activity was found in only one of the 19 patients. Although this study does not exclude an effect of the degree of blood glucose control or persistence of beta cell function in the early stages of diabetes on the subsequent development of vascular disease, it suggests that genetic factors, age of onset and plasma growth hormone levels may be more important.

Adult↗
PubMed1978

Characterization of seven C-peptide antisera.

The plasma C-peptide immunoreactivity (CPR) in 10 normal subjects varied considerably when measured with different antisera in parallel assays. The CPR level correlated with the blank "CPR" value measured in plasma devoid of C-peptide and to a lesser degree with the sensitivity of the standard curves obtained with the individual antisera. Storage of plasma samples at different temperatures and for different lengths of time before the analyses were carried out resulted in further variation in the CPR results. This was caused by a time- and temperature-dependent fall in CPR, which was more pronounced with some antisera than with others. This sensitivity to storage of plasma did not correlate with the antigenic characteristics of the antisera as determined by their reactivity with 11 specific fragments of the C-peptide molecule. The contribution of human proinsulin to the CPR concentration relative in normal subjects was considered to be negligible even though the relative immunoreactivity of human proinsulin and C-peptide ranged from 11 to 143 per cent among these antisera. These results suggest that differences in C-peptide antisera are a major reason for the variation in the concentration of circulating CPR as measured in different C-peptide immunoassays.

Animals↗
PubMed1978

beta-cell function in children with diabetes.

Although it is generally believed that insulin secretion is minimal or absent in juvenile-onset diabetes, we have found appreciable levels of C-peptide at the time of onset in 12 patients, 4 to 16 years old (9.3 +/- 4.2). Ten of them had ketonuria but none severe ketoacidosis. All entered a remission period. Most of the patients had near normal C-peptide levels during the remission, and their beta cells had the capacity to respond to a breakfast stimulation with increased insulin secretion. C-peptide and proinsulin were also determined in 98 juvenile diabetics with age at onset of 1 to 16 years (6.8 +/- 3.9) and a duration of diabetes between two and 17 years (6.7 +/- 3.4). Many were found to have persisting beta-cell function, which seems to be of importance for ensuring stability in metabolic control. Although little is known about factors that may slow or reverse the process leading to beta-cell failure, our results suggest that early detection and intensive treatment of diabetes before severe metabolic disturbances have occurred may help preserve beta-cell function.

Adolescent↗
PubMed1977

HLA-types, C-peptide and insulin antibodies in juvenile diabetes.

HLA-types were determined in 102 juvenile diabetics. HLA-B8 was found in 39 patients (RR 2.64; p less than 0.01) and HLA-BW15 in 32 patients (RR 1.33; n.s.). HLA-B7 was found in 14 patients (RR 0.40; p less than 0;05). There were no correlations between HLA-B8 or BW15 and family history of diabetes, occurrence of infection before onset of diabetes, ketonuria at onset or the age at onset of diabetes. Serum C-peptide, insulin binding capacity of IgG and total serum insulin, IRI, were determined in 94 patients who had had diabetes for more than two years and who were beyond the remission period. Measurable amounts of C-peptide were found in 33 patients (34.7%). There was no evidence of a relationship between any particular HLA-antigen and the B-cell function except for an increased incidence of do a decreased incidence of detectable C-peptide in patients with the combination HLA-B8, W15. Only four patients (4.3%) were lacking insulin antibodies; HLA-BW15 positive patients had higher levels of insulin antibodies than other groups, while HLA-B7 positive patients had lower levels; The results suggest that HLA-B7 and HLA-B18 might be associated with a different and perhaps milder form of juvenile diabetes.

Adolescent↗