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Biomedical subjects

G J Bruining

Publications and source records attributed to G J Bruining.

At least 55 records · Page 3Linked to original sources
PubMed1989

Continuous subcutaneous insulin infusion (CSII) versus conventional injection therapy in newly diagnosed diabetic children: two-year follow-up of a randomized, prospective trial.

The effect of continuous subcutaneous insulin infusion (CSII), begun at diagnosis, on blood glucose control and endogenous insulin production was studied in a group of consecutively referred newly diagnosed diabetic children. In a random order, 15 children started CSII (age 9.5 +/- 4.2 (+/- SD) years) and 15 conventional injection therapy (age 7.0 +/- 3.6 years). For 2 years HbA1 and urinary C-peptide were measured monthly, C-peptide responses to glucagon 6-monthly, and insulin antibodies every 3 months. None of the patients requested change of therapy during the study period, but at 28 months 1 adolescent girl changed to injection therapy from CSII. Severe hypoglycaemia was observed once in each group, but ketoacidosis only once, in the injection therapy group. From 2 months after diagnosis onwards the CSII group had significantly lower HbA1 levels. Urinary and plasma C-peptide levels did not differ between the two groups and similar insulin doses were used throughout the study. At the end of the 2 years of therapy, the CSII group had significantly lower insulin antibody levels. The observations suggest that CSII is well accepted in newly diagnosed children and improves metabolic control, but does not prolong endogenous insulin production.

Blood Glucose↗
PubMed1988

Urinary C-peptide: a useful tool for evaluating the endogenous insulin reserve in cohort and longitudinal studies of diabetes in childhood.

Increasing research into the remission phase of type I diabetes mellitus stresses the importance of a non-traumatic and reliable method for the evaluation of endogenous insulin production. We compared 24-h urinary C-peptide excretion (UCE) with plasma C-peptide values before and after stimulation with 1 mg glucagon in 24 type I diabetic children. Fasting plasma C-peptide values and stimulated plasma C-peptide values showed a linear correlation with 24 h UCE. Mean plasma C-peptide levels correlated inversely with the exogenous insulin dose. A slightly better correlation was found between the exogenous insulin dose and 24 h UCE. Control data of 24 h UCE were obtained from healthy siblings. A linear correlation with age was found up to 10 years of age above which UCE values seem to reach a plateau. This effect of age, as well as the frequency of sampling was taken into account in the derivation of 95% reference intervals for UCE. The measurement of 24 h UCE appears to be a useful parameter to assess endogenous insulin production in diabetic children, provided that age is taken into account.

C-Peptide↗
PubMed1987

Studies on insulin secretion by monolayer cultures of normal and tumorous human pancreatic cells. Effects of glucose, somatostatin and SMS 201-995.

Recently, somatostatin analogs have been introduced which can be used clinically in the treatment of tumorous or functional hypoglycemia. In the present study we investigated in vitro the regulation, the degree of autonomy and the sensitivity to natural somatostatin and its analog SMS 201-995 of insulin secretion by monolayer cultures of human pancreatic cells obtained from patients with insulinomas and from a newborn with nesidioblastosis. All cultures released insulin upon the addition of dibutyryl-cAMP and calcium, demonstrating their intact viability. Insulin secretion from nontumorous pancreatic cells surrounding an insulinoma was dose-dependently stimulated by glucose. In contrast, insulin release by B cells from a patient with nesidioblastosis and from 2 insulinomas was not stimulated by the addition of glucose. Native somatostatin (SRIF) and the synthetic analog SMS 201-995 inhibited insulin secretion from all cultures. The inhibitory effects of SRIF and SMS in the culture from the nesidioblastosis tissue, could be reversed by the addition of 11.2 mmol glucose/l, but not in one of the insulinoma cultures. This demonstrates that some sensitivity to glucose is present in B cells from the nesidioblastosis tissue, despite the unresponsiveness to glucose alone. Insulin release by insulinoma cells was blocked by somatostatin, while it was inhibited to some extent only in the cultures of nontumor B cells and of cells from the nesidioblastosis tissue. In conclusion, it was shown that insulin release by the cultured B cells obtained from several pathological conditions differed with regard to the autonomy of hormone release (glucose sensitivity) and the sensitivity to somatostatin and its analog.

Adenoma, Islet Cell↗
PubMed1987

Vitrification of mouse islets of Langerhans: comparison with a more conventional freezing method.

The possibility of cryopreservation of islets of Langerhans by vitrification using a mixture of cryoprotectants was investigated and the results were compared with a more conventional freezing method using Me2SO as cryoprotectant. Isolated mouse islets were divided into three groups: (1) control islets cultured for 6 days, (2) islets which were cryopreserved by vitrification after 2 days of culture, and (3) islets frozen in 1.5 M Me2SO after 2 days of culture. After warming, islets from groups 2 and 3 were cultured for 4 days. The thus treated islets were investigated with respect to insulin secretion in the presence of 2.5 or 25 mM glucose, survival during postwarming culture, morphology, and capability to reverse streptozotocin-induced diabetes. The insulin secretion in islets from all groups could be stimulated by a factor 5 or more by an increase in the concentration of glucose from 2.5 to 25 mM. The secretion of insulin in the presence of 2.5 mM glucose was similar in all groups of islets. The secretion of insulin in the presence of 25 mM glucose was slightly but not significantly lower in the cryopreserved islets than in the control noncryopreserved islets. The survival of islets during postwarming culture was comparable after cryopreservation with both methods, and islets from both groups could lower serum glucose in streptozotocin diabetic mice. We conclude that islets cryopreserved by the vitrification method are functional in vitro and in vivo. This method is quick, simple, and cheap because the use of complicated freezing equipment is avoided.

Animals↗
PubMed1987

Vitrification of human islets of Langerhans.

Cryopreservation of human islets of Langerhans by vitrification was studied. Isolated islets were divided into four groups: (1) control islets which were cultured for 6 days, (2) islets which were vitrified after 2 days of culture, (3) control islets which were cultured for 10-13 days, and (4) islets which were vitrified after 6-9 days of culture. After warming, islets from groups 2 and 4 were cultured for 4 days. The thus treated islets were investigated with respect to insulin secretion in the presence of 2.5 or 25 mM glucose, capacity to survive during postwarming culture, and morphology. The insulin secretion in islets from all groups could be stimulated by an increase of the concentration of glucose from 2.5 to 25 mM. No significant differences were observed between the insulin secretions of the vitrified and control islets or between the islets vitrified after 2 and 6-9 days of culture. It is concluded that human islets of Langerhans cryopreserved by vitrification are functional in vitro.

Cell Survival↗
PubMed1987

Recombinant gamma interferon induces class II major histocompatibility complex antigens on insulinoma cells.

Aberrant expression of major histocompatibility (MHC) antigens has been implicated as a factor contributing to organ-specific autoimmunity, such as progressive loss of pancreatic beta cells in type 1 diabetes. We investigated the potential of a rat beta cell tumour, RINM5F, to express enhanced levels of MHC antigens in vitro. To this purpose we treated RINM5F cells in vitro with recombinant rat gamma interferon (rIF gamma). We used monoclonal antibodies to RT1.A (class I) and RT1.B (class II) antigens of the rat MHC in conjunction with flowcytometry and immunoperoxidase techniques to analyse the expression of MHC antigens. Untreated RINM5F cells express low levels of RT1.A, whereas they are negative for RT1.B. Treatment with rIF gamma appeared to increase the expression of RT1.A antigens substantially. Most importantly, RT1.B antigens were newly expressed by rat insulinoma cells in vitro after treatment with rIF gamma. To our knowledge this is the first documentation of the potential of beta cells or their derivatives to express class II MHC antigens following IF gamma-treatment. This mechanism may play an important role in the augmentation and perpetuation of insulitis leading to type 1 diabetes mellitus.

Adenoma, Islet Cell↗
PubMed1987

Antibodies to a 64,000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes.

Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (Mr) 64,000. Since IDDM seems to develop after a prodromal period of beta-cell autoimmunity, this study has examined whether 64,000 Mr antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered beta-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 Mr membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM patients were already positive in the first samples, obtained 4-91 mo before the clinical onset of IDDM, whereas 1 patient progressed to a high 64,000 Mr immunoreactivity, at a time where a commencement of a decline in beta-cell function was detected. 64,000 Mr antibodies were detected before islet cell cytoplasmic antibodies (ICCA) in two patients. In the control groups of 21 healthy individuals, 36 patients with diseases of the thyroid and 5 SLE patients, the 64,000 Mr antibodies were detected in only one individual, who was a healthy sibling to an IDDM patient. These results suggest that antibodies against the Mr 64,000 human islet protein are an early marker of beta-cell autoimmunity and may be useful to predict a later development of IDDM.

Adolescent↗
PubMed1987

Long-acting somatostatin analogue (Sandostatin) reduces late night insulinopenic ketogenesis in diabetic teenagers.

Ten diabetic teenagers were admitted into our hospital for two nights, separated by one week. In a double-blind cross-over randomized study they received either 50 micrograms of the new long-acting somatostatin analogue Sandostatin sc or placebo. All patients were between 12 and 16 years of age, C-peptide negative with a duration of diabetes of at least four years. They had either conventional therapy or insulin pump therapy. Insulin doses and diets were kept unchanged. Blood samples were taken half hourly from 17.00 h until 09.30 h the next morning from an indwelling venous catheter. Hormonal and metabolic profiles on the two nights were evaluated by means of a distribution free time sequential co-movement analysis and by the paired Wilcoxon's signed rank test. After Sandostatin was given at 22.00 h, GH levels were significantly suppressed during 4 h. During that period blood glucose was slightly but significantly lower than after placebo. The free-insulin profiles from both nights were very comparable. Co-movement analysis showed a significant correlation between glucose and free insulin variations with a 30-min backward shift of the glucose curve. However, after Sandostatin administration this relation was lost in the period between 22.00 and 07.00 h, indicating a different effect of insulin on glucose levels during the nights Sandostatin was given. Early morning glucose rises were associated with free insulin levels below 20 mU/l. This association was not altered during the Sandostatin nights. Glucagon was not suppressed by Sandostatin except at 120 min after injection, and remained unchanged during the rest of the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1987

Cryopreservation of mouse, monkey and human islets of Langerhans for transplantation purposes.

Transplantation of islets of Langerhans is a possible future therapy for insulin-dependent diabetes mellitus. In contrast to total pancreas, isolated islets of Langerhans can be treated prior to transplantation to reduce their immunogenicity. Thus the success rate in allotransplantation of islets can be increased. The isolation of large amounts of islets from human pancreas is still a problem and islets from different donors have to be collected and stored by cryopreservation. In this paper we describe the methods used in our laboratory to isolate islets of Langerhans from rodent, monkey and human pancreas. The results are presented of successful cryopreservation of these islets. Firstly, by a more conventional freezing method using dimethylsulfoxide as cryoprotectant. Secondly, by vitrification using a mixture of cryoprotectants. The latter method has not been used previously for cryopreservation of islets. The integrity of the islets before and after freezing was tested in vitro and, for mice, in vivo.

Animals↗
PubMed1986

HLA-DO polymorphism associated with resistance to type I diabetes detected with monoclonal antibodies, isoelectric point differences, and restriction fragment length polymorphism.

A new HLA-DQ-related genetic system with two alleles, 2B3 and TA10, defined serologically by MAbs and alloantisera, showed an almost perfect correlation with charge differences on DQ beta molecules, as well as with two polymorphic DNA fragments hybridizing with a DQ beta probe and various restriction enzymes on a panel of 14 DR4+ homozygous typing cells. It was therefore concluded that the serologically defined alleles 2B3 and TA10 are coded by the DQ beta gene and situated on the HLA-DQ beta chain. This 2B3/TA10 polymorphism is independent of HLA-D and segregates with HLA in families. The TA10 allele appears to be a new marker for resistance to type I diabetes, which is independent from the known resistance marker DR2, whereas no association was observed between this DQ beta polymorphism and rheumatoid arthritis.

Antibodies, Monoclonal↗
PubMed1986

Overnight metabolic profiles in very young insulin-dependent diabetic children.

UNLABELLED: The magnitude of the disturbance of metabolic control in diabetes mellitus in very young children has been recognised, but seldom studied. Limitations to studies are set by the difficulty of obtaining control data and until recently the lack of alternative therapies. Recently "mini" pumps for continuous subcutaneous insulin delivery have become available and may offer an alternative therapeutic possibility. The present investigation has been undertaken to collect overnight metabolic data of very young diabetic children (less than 6 years) controlled by standard injection therapy. During one admission to hospital frequent blood samples were collected for free insulin, glucose, alanine, lactate, glycerol and 3-hydroxybutyrate determinations. In all children (n = 9) the profiles showed a steep rise in glucose from 04.30 h (6.2 +/- 1.3 mmol/l) to 09.30 h (17.8 +/- 2.4 mmol/l) (the so-called "dawn-phenomenon"). The nature of the changes in the intermediary metabolites suggested that rise in blood glucose was caused by insufficient insulin. We have attempted to explore the time relationship between the overnight drop in free insulin levels and the rises in blood glucose by a distribution-free statistical analysis, correlating successive changes in time between the two profiles. The analysis suggested a delay of 2-6 h between free insulin levels and their effects. IN CONCLUSION: a clear "dawn phenomenon" is seen in very young diabetic children, and contributes to their poor glycaemic control. More stable and higher insulin concentrations in the early morning, obtained perhaps by continuous subcutaneous insulin infusion, might ameliorate the overall glycaemic control in the very young diabetic child.

Age Factors↗
PubMed1986

Normalization of glucose homeostasis by a long-acting somatostatin analog SMS 201-995 in a newborn with nesidioblastosis.

A female child was admitted to the hospital few days after birth with severe hypoglycemia and convulsive episodes. Plasma insulin levels were elevated and oral and intravenous administration of glucose were unable to keep blood glucose above 2 mmol/l limit. Intravenous infusion of a long acting somatostatin analog, SMS 201-995, at a dosage gradually increasing from 2 to 50 micrograms/24 hr, was accompanied by a dramatic fall in circulating insulin levels. Normality of glucose homeostasis was restored and convulsive spells ceased. Fasting blood glucose levels stabilized between 3.4 and 4.7 mmol/l. No rebound phenomenon was observed during short term interruptions of the SMS 201-995 infusion. A subtotal pancreatectomy was performed during SMS treatment, and the diagnosis of nesidioblastosis was confirmed by immunocytologic and electron-microscopic studies. It is concluded that this new potent and long acting somatostatin derivative may be useful in the management of hyperinsulinism in the neonate.

Blood Glucose↗
PubMed1985

Prediction of type 1 diabetes mellitus--a report on three cases.

In three children (patients 1, 2 and 3) insulin-dependency was predicted 28, 32 and 4 months, respectively before the disease became clinically manifest, by the finding of islet cell antibodies at that time. These retrospective findings support the evidence for a long pre-diabetic phase in childhood diabetes, marked by the presence of islet cell antibodies, as well as the linkage of HLA-antigens to the susceptibility to this disease. The possibility of detecting pre-diabetic states in children before the endogenous insulin secretion decreases to the point of producing clinical symptoms support efforts by basic scientists to develop techniques for immunological intervention early in the course of the disease.

Adolescent↗
PubMed1985

Antipyrine clearance and metabolite formation in children with congenital adrenal hyperplasia.

Antipyrine salivary clearance and half-life and the rate of formation of three principal metabolites of antipyrine (4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine) were assessed in nine children with congenital adrenal hyperplasia, six of whom were salt-losers and three of whom were non-salt-losers. No differences were found in comparison with data obtained in normal children.

Adolescent↗