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Biomedical subjects

L G Heding

Publications and source records attributed to L G Heding.

At least 37 records · Page 2Linked to original sources
PubMed1984

Pharmacokinetics of subcutaneously administered human, porcine and bovine neutral soluble insulin to normal man.

Highly purified neutral soluble human, porcine and bovine insulin (0.075 U/kg body weight) were administered randomly by subcutaneous injection to six normal men. Somatostatin by continuous intravenous infusion (100 micrograms/h) was used to suppress endogenous insulin secretion. The effects of the three species of insulins on plasma glucose, immunoreactive insulin (IRI), C-peptide and intermediary metabolite concentrations were essentially similar. The onset of hypoglycaemic action of bovine insulin was delayed compared to human and porcine insulin due possibly to a lower receptor binding of the bovine insulin. No local or systemic adverse reactions to the insulins were observed.

3-Hydroxybutyric Acid↗
PubMed1984

Plasma proinsulin and C-peptide concentrations in children with hyperinsulinaemic hypoglycaemia.

Plasma concentrations of proinsulin and C-peptide were measured in five children presenting with severe hypoglycaemia associated with elevated plasma levels of immunoreactive insulin (IRI) in order to determine whether the profile of circulating B-cell products related to the underlying pathophysiology of the pancreas. Results were compared with data from 13 normal infants. Four children, three neonates and a nine year old girl, were subjected to partial or total pancreatectomy. The neonates had nesidioblastosis, nesidioblastosis with a microadenoma, and a functional abnormality without histological derangement respectively; the older child had a localised adenoma. The remaining child, a neonate, had transient hypoglycaemia and elevated IRI levels associated with hyperlactataemia and hyperalaninaemia. All the children had markedly elevated plasma proinsulin concentrations; the highest levels were seen in the child with an isolated adenoma and in the neonate with nesidioblastosis and a microadenoma. Both of these children also had substantially elevated plasma C-peptide concentrations. The remaining three neonates had plasma C-peptide levels, which although in the normal range for normoglycaemia were inappropriately elevated during hypoglycaemia. It is concluded that elevated proinsulin and C-peptide concentrations are seen in children with hypoglycaemia associated with increased plasma IRI levels and that the profile of the concentrations does not provide a reliable marker for the nature of the underlying pancreatic abnormality.

Alanine↗
PubMed1984

Human and porcine insulins are equally effective in the regulation of glucose kinetics of diabetic patients during exercise.

The rate of hepatic glucose production (Ra) and peripheral utilization (Rd) was determined in 8 insulin-dependent diabetic subjects in basal state and during 40 min cycle ergometric exercise. The patients were treated with continuous sc infusion of either semisynthetic human or porcine (Actrapid) insulin. Basal rate of glucose production was comparable during human (2.29 +/- 0.19 mg/kg/min) and porcine (2.18 +/- 0.12 mg/kg/min) insulin therapy. In response to exercise, Ra rose 30 to 40% (P less than 0.05), to 2.85 +/- 0.35 vs 3.18 +/- 0.42 mg/kg/min, similarly during both studies. The peak rise in Rd (to 3.20 +/- 0.32 during human vs 3.78 +/- 0.44 mg/kg/min during porcine insulin) was comparable in both groups and not significantly different from the rise in Ra. Consequently, blood glucose levels remained unchanged. During the exercise tests, the metabolic conditions were stable and comparable in both studies, as indicated by similar levels of blood glucose, plasma free insulin HbA1, serum lipids and insulin binding to erythrocytes. In conclusion, semisynthetic human insulin is equally effective as porcine insulin in regulating glucose kinetics in the basal state and during exercise.

Adult↗
PubMed1983

Pancreatic A and B cell hyperfunction in the Mendenhall syndrome.

A 16-year-old boy with persistent hyperglycaemia (approximately 16 mmol/l in the fasting state) and acanthosis nigricans had insulin resistance and received daily up to 2800 U of short-acting, soluble, highly purified porcine insulin. The number and affinity of insulin receptors were markedly decreased. No significant insulin binding to IgG could be detected. Immunoreactive insulin varied between 1344 and 2400 mU/l. Endogenous insulin secretion and proinsulin levels were grossly elevated in the fasting state (C-peptide 2.2-3.5 pmol/ml; proinsulin approximately 1 pmol/ml). After an oral glucose tolerance test and intravenous arginine infusion, B cell hypersecretion was confirmed. The molar ratio of C-peptide to immunoreactive insulin, normally approximately 7, was about 0.3, clearly indicating that most of the immunoreactive insulin was exogenous. The molar ratio of proinsulin to C-peptide, which is about 0.05 in fasting control subjects, was 0.23-0.45, clearly showing that too high a proportion of proinsulin was being secreted. This may indicate that the constant hyperstimulation of the B cell leads to reduced conversion of proinsulin to insulin. Immunoreactive glucagon levels were within normal limits fasting but were above normal after intravenous arginine infusion. Thus, in this case of diabetes with acanthosis nigricans, the severe insulin resistance, probably caused by a receptor defect, was associated with markedly increased B cell function.

Acanthosis Nigricans↗
PubMed1983

Serum levels of true insulin, C-peptide and proinsulin in peripheral blood of patients with cirrhosis.

The levels of proinsulin, immunoreactive insulin, true insulin (calculated from the difference, namely immunoreactive insulin-proinsulin) and C-peptide were determined in the fasting state and during a 3-h oral glucose tolerance test after administration of 100 g of glucose in 12 patients with cirrhosis with normal oral glucose tolerance test (50 g) and in 12 healthy subjects serving as controls. In the patients with cirrhosis the serum levels of proinsulin and immunoreactive insulin were significantly higher in the fasting state and after glucose loading than in the healthy subjects. The serum level of true insulin was also higher in the patients with cirrhosis, but the difference was less pronounced and only significant at a few of the time points. The serum level of C-peptide was very similar in both groups. These results emphasize that cirrhosis is a condition in which the serum proinsulin level is raised and that this hyperproinsulinaemia contributes greatly to the increased immunoreactive insulin levels observed in patients with this disease.

Adult↗
PubMed1983

Residual B cell function in diabetic children as determined by urinary C-peptide.

C-peptide was determined in 24-h urine collections and in fasting plasma of 27 Type 1 (insulin-dependent) diabetic children (duration of disease 0-6 years) and in 11 matched normal children. Grouping the patients according to duration of disease from onset to 6 years, it was found that in the first year of disease the B cell reserve was a mean of 4.89 +/- 1.95 pmol X mg creatinine-1. 24 h-1 compared with a mean of 24.51 +/- 2.91 pmol X mg-1 X 24 h-1 in the control group. A further diminution was seen with increase in the duration of disease, until after 6 years when only traces of C-peptide could be detected. There was a good correlation between the levels of plasma C-peptide and urinary C-peptide values as related to creatinine (r = 0.89; p = less than 0.001). In view of this, and since it is simpler and less traumatic to obtain frequent urine samples from children than it is to obtain blood samples, it was felt that the determination of urinary C-peptide constitutes a valuable tool in the evaluation of the diabetic child.

Adolescent↗
PubMed1983

Human insulin. Facts and perspectives.

Recently an improved process for the production of human insulin from porcine insulin has been described. After being characterized, this insulin has been tested and shown to be safe and effective in diabetics in a short-term, double-blind, cross-over study. The availability of sufficient quantities of this human insulin now permits short- and long-term clinical investigations of the possible benefits of human insulin in the treatment of diabetics.

Animals↗
PubMed1982

Fetal beta cell function in diabetic pregnancy. Amniotic fluid concentrations of proinsulin, insulin, and C-peptide during the last trimester of pregnancy.

Proinsulin, insulin C-peptide, insulin-binding antibody, and glucose concentrations were measured in amniotic fluid samples from 43 insulin-treated diabetic patients and 17 nondiabetic control patients between the thirty-six and thirty-ninth weeks of gestation. Insulin-binding antibodies in amniotic fluid were present in only three diabetic patients, although antibodies in maternal serum were found in 22 of the diabetic subjects. In the diabetic group, maternal serum insulin-binding antibodies were statistically unrelated to levels of C-peptide in amniotic fluid. The mean amniotic fluid concentrations of proinsulin (0.07 nmole/L), insulin (0.08 nmole/L), C-peptide (1.17 nmoles/L), and glucose (2.09 mmoles/L) were markedly elevated (p less than 0.001) in diabetic patients, as compared to nondiabetic control patients, thus suggesting exaggerated fetal beta cell function. C-peptide was correlated to both insulin (r = 0.69) and proinsulin (r = 0.35) in the diabetic group only. Infant birth weight and amniotic fluid C-peptide was significantly correlated in both the control group (r = 0.54) and the diabetic group (r = 0.38). Diabetic pregnancies associated with neonatal morbidity (n = 25) had significantly higher mean amniotic fluid concentrations of both insulin and C-peptide than did pregnancies without neonatal morbidity (n = 18). The amniotic fluid values of C-peptide and insulin in these latter two subgroups were overlapping and, therefore, could not serve to predict neonatal outcome in the individual case.

Adult↗
PubMed1982

Serum C peptide and IRI levels after administration of glucagon and glucose in non-insulin-dependent diabetics.

A comparative study was carried out on B cell response to alternative intravenous glucagon (1.0 mg) and intravenous glucose (0.33 g per kg body weight) in healthy non-obese persons (c-NOb), healthy obese persons (C-Ob), non-obese non-insulin-dependent diabetics (NIDD-NOb) and obese non-insulin-dependent diabetics (NIDD-Ob). Each group comprised ten subjects. C-peptide (CP immunoassay using antiserum M 1230) and IRI in the serum were measured for each test. After glucose load in B-cell responses were significantly lower in both the diabetic groups than in the normal groups. After glucagon injection there were no significant differences in IRI and CP levels between NIDD-NOb and C-NOb, however, significantly lower levels of serum CP were noted among NIDD-Ob in comparison to C-Ob with a lack of these differences in IRI levels. This phenomenon is well reflected by the molar IRI/CP ratio expressed as a percentage. In the fasting state IRI accounted in C-Ob for 8.8 +/- 3.5 per cent of CP, while in NIDD-Ob for up to 25. +/- 10.4 percent of CP (P = 0.0004). In the latter group of patients, the IRI/CP ratio after glucagon reached the highest values (over 30 per cent) observed in this study. These data suggest the important role in insulin disposal played by the liver in non-insulin-dependent diabetes associated with obesity. Another explanation for these data is that more proinsulin is secreted in this group of patients as compared to other groups.

C-Peptide↗
PubMed1982

Nonspecific blinding of insulin to gamma globulin in the serum of black patients with hepatocellular carcinoma and other forms of liver disease.

The study was prompted by the apparent detection of insulin antibodies in a black patient with HCC and recurrent hypoglycemia who had never received insulin. It consisted of two parts. Initially the sera of 30 individuals (six normoglycemic HCC patients, three with HCC and recurrent hypoglycemia, 11 patients with noncancerous liver diseases, and 10 healthy black controls) were analyzed for the presence of insulin (and glucagon) antibodies by precipitating the bound, labeled hormone with ethanol and also by the technique of radioimmunoelectrophoresis. In the nine HCC patients, binding of 125I-insulin averaged 13% by ethanol separation and 0.018 mU/ml with radioimmunoelectrophoresis, levels that were similar to those of patients with noncancerous liver disease and significantly higher than those of the healthy controls. Mean binding of 125I-glucagon was 11% in HCC sera. Serum binding of labeled hormones correlated significantly with IgG concentrations in the patients. The second part of the study attempted to define the nature of insulin binding in HCC and other forms of liver disease. After confirmation of the increased serum binding of labeled insulin by another method of precipitation, PEG, an attempt was made to compete with the labeled insulin for its serum binding sites by adding a large amount of unlabeled insulin. This binding was not displaceable, however, and was therefore considered nonspecific. When the same procedures were repeated using normal serum to which increasing amounts of gamma globulin were added, the nonspecific binding of insulin increased in a linear fashion. Furthermore, a similar degree of high nonspecific insulin binding occurred in six patients with multiple myeloma and raised serum IgG concentrations. We therefore conclude that in the many clinical situations where hypergammaglobulinemia exists, false positive tests for the detection of antibodies against insulin (and probably other peptide hormones) will emerge unless appropriate methods are used to check for nonspecific peptide binding.

Black People↗
PubMed1982

A study of the comparative safety and efficacy of neutral soluble human (semi-synthetic) and porcine monocomponent insulin in non-diabetic subjects.

Neutral soluble human (semi-synthetic) and porcine insulin and diluting medium were administered subcutaneously in a randomized fashion to six fasting normal male subjects. The plasma glucose, C-peptide and insulin response was observed for a period of two hours before and six hours after injection of insulin (0.075 m/kg) into the anterior abdominal wall. The hypoglycaemic response was identical for the two insulins with the plasma glucose values reaching a nadir at 90--120 minutes and returning to within 10% of basal levels by six hours. Also similar peak plasma insulin values were achieved with human and porcine insulin by 50--60 minutes post-injection. The C-peptide response following the administration of both insulins suggested equal suppression of endogenous beta cell secretion. The two insulins were well tolerated with no immediate or delayed allergic reactions in any subject. These results suggest that human (semi-synthetic) and porcine soluble monocomponent insulins under the described experimental conditions are bioequivalent.

Adult↗
PubMed1981

Comparative study of subcutaneous, intramuscular, and intravenous administration of human insulin.

Human insulin derived from porcine insulin was given subcutaneously (s.c.), intramuscularly (i.m.), and intravenously (i.v.) to normal men. The dosage for all three routes was 0 . 075 IU/kg body weight. Diluting medium was administered by s.c. injection to obtain control values. Somatostatin (100 microgram/h) was given to inhibit pancreatic beta cell secretion. The plasma glucose responses to s.c. injection of this insulin into the anterior abdominal wall and to i.m. injection into the thigh were similar with respect to the extent, onset, and duration of effect. Plasma glucose fell from mean (+/- SE) pre-injection values of 4 . 3 +/- 0 . 15 and 4 . 4 +/- 0 . 27 mmol/l, to 3 . 06 +/- 0 . 25 and 2 . 98 +/- 0 . 16 mmol/l by 90 to 105 min for s.c. and i.m. studies, respectively, thereafter returning to mean basal level by 6 h after i.m. injection, but remaining about 0 . 5 mmol/l below basal level after s.c. injection. A much more sudden, but short-lived, hypoglycaemic response occurred after i.v. insulin, with plasma glucose failing from 4. 50 +/- 0 . 42 to 1 . 45 +/- 0 . 16 mmol/l by 25 min, returning to mean basal value after 3 1/2 h. The mean (+/- SE) peak insulin levels after s.c. and i.m. injection were 0 . 13 +/- 0 . 01 and 0 . 18 +/- 0 . 04 pmol/ml at 90 and 60 min, respectively. After i.v. injection the maximum plasma insulin concentration of 6 . 9 +/- 0 . 73 pmol/ml was seen at 2 min. No adverse side-effects were observed.

Adult↗
PubMed1981

Human insulin: study of safety and efficacy in man.

The safety and efficacy of a new highly purified neutral soluble human insulin produced by conversion of porcine insulin was compared with a highly purified neutral soluble porcine insulin in six normal men. The insulins were administered by subcutaneous injection at a dose of 0.075 U/kg body weight. Somatostatin was infused during the experiment to suppress endogenous insulin secretin. No difference was found in the plasma glucose, insulin, or metabolite responses. Thus the potency, onset, and duration of effect were identical with the two insulins. No short-term side effects to either insulin were observed. Highly purified, semi-synthetic human insulin offers a safe and effective means to explore the possible advantages of homologous human insulin in the management of diabetes mellitus.

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

Glucagon: structure-function relationships investigated by sequence deletions.

A series of glucagon analogues, des-(1-4)-glucagon, des-(5-9)-glucagon, des-(10-15)-glucagon, des-(16-21)-glucagon, des-(22-26)-glucagon and des-(27-29)-glucagon, were prepared by condensation of synthetic fragments and characterized biologically and immunologically. Fully synthetic glucagon was also characterized. The potencies with regard to glucagon receptor binding in purified rat liver plasma membranes were, in decreasing order: synthetic glucagon 108%, des-(1-4)-glucagon 5.7%, des-(27-29)-glucagon 0.92%, des-(5-9)-glucagon 0.47%, des-(10-15)-glucagon 0.0028%, des-(16-21)-glucagon 0.0017% and des-(22-26)-glucagon 0.00060% relative to that of natural porcine glucagon. Des-(27-29)-glucagon was the only analogue that activated the adenylate cyclase in rat liver plasma membranes or stimulated the lipolysis in isolated free fat cells from rat epididymal fat pad. The potencies were 0.16% and 0.20% of that of glucagon, respectively. Des-(1-4)-glucagon was a glucagon antagonist in the adenylate cyclase assay. The immunoreactivities of the glucagon analogues were determined with two commonly used anti-glucagon sera, K 5563 and K 4023, directed towards the C-terminus and some segment in the sequence 2-23, respectively. In the K 5563 assay, des-(27-29)-glucagon and des-(22-26)-glucagon had potencies of 0.0009% and less than 0.09% of that of glucagon, respectively. The remaining analogues had potencies varying from 45% to 141% of that of glucagon. In the K 4023 assay, the analogues showed a non-linear dilution effect. The combined results indicate a partition within the glucagon molecule with regard to receptor binding and adenylate cyclase activation. The region 10-26 appears to be the most important for receptor binding, whereas 1-4 is essential for adenylate cyclase activation. The C-terminal segment 27-29 is important for the maintenance of full receptor binding but non-essential for adenylate cyclase activation.

Adenylyl Cyclases↗