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Biomedical subjects

A Lernmark

Publications and source records attributed to A Lernmark.

At least 217 records · Page 12Linked to original sources
PubMed1989

Increased levels of circulating immune complexes are not associated with diabetes in BB rats.

Increased levels of circulating immune complexes (IC) have been described in insulin-dependent diabetic (IDD) patients at the time of diagnosis. The aim of the present study was to test whether the spontaneously diabetic BB rat had changes in IC levels at different ages prior to and at onset of IDDM as compared with diabetes resistant BB rats and normal Wistar Furth rats. The IC levels were related to serum IgG concentration as well as to total peripheral blood lymphocyte counts. Three groups of rats with 12 animals in each were followed: Diabetes-prone, lymphopenic (DP) BB rats with an expected high incidence of diabetes, diabetes-resistant (DR) BB rats from the non-diabetic w-subline, and Wistar Furth rats. Blood samples collected on 12, 22, 29, 43, 71, and 99 days of age were analyzed for IC, detected in a solid phase C1q assay, serum IgG levels, and peripheral blood lymphocytes. Diabetes developed in 8/12 (66%) DP BB rats between 70 and 93 days of age while none of the DR BB rats developed diabetes. The levels of IC tended to increase with age in all three groups of rats and did not differ between DP BB and Wistar rats whereas DR BB rats had significantly higher levels (p less than 0.05-0.01) at all ages. The profile of serum IgG was similar in all rats showing a high level at 12 days of age and a nadir at day 29 followed by an increase from day 43 until the end of the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Islet beta-cytotoxic monoclonal antibody against glycolipids in experimental diabetes induced by low dose streptozotocin and Freund's adjuvant.

Diabetes was induced in BALB/c mice by four injections of a subdiabetogenic dose (40 mg/kg) of streptozotocin in combination with CFA. The treatment increased the plasma glucose from 5.8 +/- 0.1 to 22.1 +/- 1.3 mmol/liter (n = 9). The diabetic animals had circulating islet cell surface antibodies (75%), and a monoclonal islet cell surface IgM antibody, K56aF3, generated from one of the diabetic BALB/c mice, mediated C-Dependent cytotoxicity against insulin-producing cells and inhibited glucose-stimulated insulin release from isolated rat islets. Solid phase assay on thin layer chromatograms showed no binding of the K56aF3 antibody to glycolipids prepared from relevant cells. However, testing against a series of glycolipids of various non-pancreatic origins showed a preferential binding to a nine-sugar glycolipid isolated from human erythrocytes carrying an unusual blood group A determinant (type 3). It is suggested that this mAb may be associated with the development of diabetes following a combination of polyclonal activation and non-diabetogenic doses of streptozotocin.

Animals↗
PubMed1988

Serum exchange and use of dilutions have improved precision of measurement of islet cell antibodies.

In an attempt to improve the diagnostic value of measuring antibodies to islet cell cytoplasmic antigen, coded sera were distributed to 38 laboratories and results were returned for analysis. Comparison between laboratories revealed that results for some individual sera differed by up to nine doubling dilutions and even within laboratories duplicate samples could differ by six doubling dilutions. By including dilutions of sera it was possible to draw a standard curve for each laboratory and this revealed major variations in shape, slope and intercept. However, using each laboratory's standard curve and converting results to units, a substantial improvement was obtained. The approach described improves standardisation and will permit laboratories to identify poor precision and/or any systematic change in assay performance.

Animals↗
PubMed1988

Antibodies to a Mr-64,000 islet cell protein in Swedish children with newly diagnosed type 1 (insulin-dependent) diabetes.

Sera from 40 Swedish children diagnosed as having Type 1 (insulin-dependent) diabetes mellitus during a one year period along with 40 age and geographically matched control subjects were tested for antibodies to a Mr-64,000 islet protein by immunoprecipitation of 35S-methionine-labelled rat islet amphiphilic proteins. Of the 40 diabetic patients, 29 (73%) were found to be positive whereas all 40 control subjects were negative. Samples were also tested for titres of islet cell cytoplasmic antibodies by indirect immunofluorescence on frozen sections of human pancreas. In the diabetic group, 30 of the 40 patients (75%) were positive for islet cell cytoplasmic antibodies compared with 2 of the 40 control subjects (5%). A comparison of levels of antibodies to the Mr-64,000 protein with islet cell cytoplasmic antibodies revealed a weak (rs = 0.46), but significant (p less than 0.01) correlation between the two tests. There was no effect of age or sex on levels of antibodies to the Mr-64,000 protein. These results in population-based diabetic children and control subjects demonstrate a high frequency of antibodies to the Mr-64,000 protein at the time of clinical onset.

Animals↗
PubMed1988

Factors influencing the magnitude, duration, and rate of fall of B-cell function in type 1 (insulin-dependent) diabetic children followed for two years from their clinical diagnosis.

The pattern of fall in B-cell function measured as plasma and 24 h urinary C-peptide excretion, as well as levels of islet cell antibodies, insulin antibodies and metabolic parameters, were followed for two years in 39 children aged 1-17 years prospectively from clinical onset of Type 1 (insulin-dependent) diabetes. At onset 32/36 patients had measurable plasma C-peptide (median 0.13 nmol/l). Maximum values of fasting and postprandial plasma C-peptide were reached at a median duration of three months. Thereafter both plasma and urinary C-peptide declined linearly. The median value of the rate of fall in postprandial plasma C-peptide was 0.019 nmol.1-1.month-1. Age at onset was positively correlated to the maximum value of postprandial plasma C-peptide in each patient (rs = 0.57, p = 0.0001) and throughout the observation time positively correlated to fasting and postprandial C-peptide and to the 24 h urinary C-peptide excretion (rs range 0.35-0.70, p = 0.03-0.0001). The rate of fall of postprandial C-peptide was unrelated to age at onset and was strikingly parallel in different age groups. Islet cell antibodies were present in 87% of the patients at onset and decreased to 38% at 24 months. Islet cell antibody titres were not correlated to age at onset or to plasma or urinary C-peptide at any single observation. However, islet cell antibody negative patients had significantly higher (p less than 0.05) postprandial plasma C-peptide values at 1, 9, and 12 months of duration, compared to islet cell antibody positive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Gene probes to detect cross-culture contamination in hormone producing cell lines.

Cross-culture contamination of cell lines propagated in continuous culture is a frequent event and particularly difficult to resolve in cells expressing similar phenotypes. We demonstrate that DNA-DNA hybridization to blotted endonuclease-digested cell DNA effectively detects cross-culture contamination to monitor inter-species as well as intra-species cross contamination. An insulin-producing cell-line, Clone-16, originally cloned from a human fetal endocrine pancreatic cell line did not produce human c-peptide as anticipated. DNA from these cells showed no hybridization to the human ALU sequence probe, BLUR, and lacked restriction fragment length polymorphism typical for the human HLA-DQ beta-chain gene. Although a human insulin gene probe showed a weak, nonhuman hybridization pattern, a cDNA probe for the Syrian hamster insulin gene hybridized strongly consistent with a single copy hamster insulin gene. Karyotyping confirmed the absence of human chromosomes in the Clone-16 cells while sizes, centromere indices, and banding patterns were identical to Syrian hamster fibroblasts. We conclude that the insulin-producing Clone-16 cells are of Syrian hamster origin and demonstrate the effective use of gene probes to control the origin of cell cultures.

Adenoma, Islet Cell↗
PubMed1988

Secretin uncouples glucose inhibition of glucagon-producing cells resulting in a simultaneous stimulation of both glucagon and insulin release.

The effect of secretin on glucagon and insulin release and its interaction with glucose has been studied in cultured mouse pancreatic islets by column perifusion. Glucose alone showed the well-known stimulation of insulin release and inhibition of glucagon release. Addition of 10 mM secretin increased glucagon secretion at 3 mM D-glucose by 300% while no change in insulin release could be seen at this low glucose concentration. At maximal stimulation of insulin release by 20 mM D-glucose addition of 10 nM secretin increased insulin release by 30%. Despite this insulin concentration and the high glucose concentration an increase in glucagon secretion of 1800% was found. These effects of secretin were dose-dependent at 10 mM D-glucose with 1 nM secretin being the lowest effective dose.

Animals↗
PubMed1988

Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo.

The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. We propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression.

Adenoma, Islet Cell↗
PubMed1988

Reduced pancreatic insulin is associated with retarded growth of the pancreas in young prediabetic BB rats.

The beta-cell function in the perfused pancreas, the total pancreatic insulin content, and the weights of pancreas, kidney, spleen, and total body fat were compared at the age of 30 and 45 days in diabetes-prone and body weight-matched diabetes-resistant male BB rats. These inbred rats had an incidence rate of diabetes at 90 days of age of 80 and 0%, respectively. At day 30, the pancreatic insulin content was reduced in the diabetes-prone (n = 10) rats to 15 micrograms (range 7.7-31.8) compared with 32 micrograms (range 23.3-52.9) in the diabetes-resistant (n = 10) rats (p less than 0.01). Although the kinetics of insulin release in response to glucose was maintained, the amount of insulin released in the diabetes-prone rats was decreased (p less than 0.05) including the first peak (p less than 0.05). The weight of the spleen was less (p less than 0.05); whereas the weights of the pancreas, kidney, and total body fat did not differ from those observed in the diabetes-resistant control rats. At 45 days of age, the weight of the pancreas in the diabetes-prone rats (n = 8) was reduced to 159 mg (range 100-190) from 202 mg (range 185-214) (p less than 0.01). The body weight and body fat were identical to those observed in the diabetes-resistant controls (n = 8) and their kidney (p less than 0.05) and spleen (p less than 0.01) were larger. The insulin content was reduced to the same magnitude as the reduction of pancreatic weight.

Adipose Tissue↗
PubMed1988

Insulin release by glucagon and secretin: studies with secretin-glucagon hybrids.

Secretin and glucagon potentiate glucose-induced insulin release. We have compared the effects of secretin and glucagon with that of four hybrid molecules of the two hormones on insulin release and formation of cyclic AMP (cAMP) in isolated mouse pancreatic islets. All six peptides potentiated the release of insulin at 10 mM D-glucose, and their effects were indistinguishable with respect to the dynamics of release, dose-response relationship, and glucose dependency. However, measurements of cAMP accumulation in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-4) M) showed that the fold increase compared with glucose alone had the following ranking order: secretin = [Tyr10, Tyr13]-secretin 1.6 less than [Tyr10, Tyr13, Trp25]secretin 1.8 less than glucagon 1.9 less than [Asp3, Glu9, Arg12]glucagon 2.3 = [Asp3, Glu9]glucagon. These results suggest that despite similar potentiating effects of secretin and glucagon on glucose-induced insulin release, their modes of action may be different.

Amino Acid Sequence↗
PubMed1988

Interleukin-1 potentiates glucose stimulated insulin release in the isolated perfused pancreas.

The acute effects of recombinant human interleukin-1 beta (rIL-1) on basal and glucose-stimulated insulin release were investigated in the isolated perfused pancreas. At a concentration of 20 micrograms/l rIL-1 had no effect on basal insulin release, but increased the total amount of insulin released during first and second phase insulin release in response to 20 mmol/l D-glucose in the rat pancreas (P less than 0.05). In addition, 26 micrograms/l of rIL-1 potentiated insulin release in response to square wave infusions of stimulatory concentrations of glucose (11 mmol/l) in the porcine pancreas. We hypothesize that IL-1 in the systemic circulation may affect B cell function in vivo.

Animals↗
PubMed1988

Nonislet pancreatic autoantibodies in sibship with permanent neonatal insulin-dependent diabetes mellitus.

Neonatal insulin-dependent diabetes mellitus (IDDM) occurs rarely. A sibship of two HLA-Dw3/4-positive boys who developed IDDM within the 1st wk of life is described. Although the HLA-D region genotype would be consistent with IDDM associated with islet autoimmunity, islet cell antibodies were negative, but both boys exhibited the presence of a novel autoantibody that reacted specifically with a conspicuous, yet unidentified, determinant in the interstitial tissue among the acinar cells. The possible relationship between this acinar nonislet autoantibody and permanent neonatal diabetes remains to be established.

Autoantibodies↗
PubMed1987

Prolonged incubation in the two-colour immunofluorescence test increases the prevalence and titres of islet cell antibodies in type 1 (insulin-dependent) diabetes mellitus.

The conventional indirect immunofluorescence test of islet cell antibodies was recently improved by the development of a two-colour immunofluorescence assay using a monoclonal proinsulin antibody to detect islet B cells. The aim of this study was to test whether in this new assay the prevalence and titre of ICA were affected by the time of incubation carried out in the presence of aprotinin (Trasylol) as an inhibitor of proteolysis. The end-point titre of ICA was therefore determined in sera from 70 children aged 0.6 to 15 years with recent onset Type 1 (insulin-dependent) diabetes mellitus, 50 healthy control subjects and 97 non-diabetic siblings of Type 1 diabetic children. In the conventional two-colour assay, ICA was positive in 53/70 (76%) Type 1 diabetic patients, 1/50 control subjects and 2/97 siblings after 30 min incubation. Prolonged incubation for 18 h increased the prevalence of ICA positive samples to 62/70 (89%) in the diabetic patients and to 2/50 in the control subjects, while the prevalence among the siblings was unchanged. Of the ICA positive non-diabetic subjects, one control child has a father with Type 1 diabetes, and one of the siblings subsequently developed Type 1 diabetes. In the diabetic patients the median titre was 1:32 for the 30 min incubation, and it increased to 1:64 for the 18 h incubation (p less than 0.001). A marked prozone effect was seen; 16% of the samples from the Type 1 diabetic children sera were negative at a 1:2 dilution, but were found positive at higher dilutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗