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  • 1
    ISSN: 1432-0428
    Keywords: Dog ; insulin therapy ; mathematical model ; soluble insulin ; depot insulin ; absorption ; subcutaneous
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The appearance rate of insulin (calculated insulin secretion rate) in the circulating blood after subcutaneous injection was estimated in diabetic dogs from serial measurements of immunoreactive insulin concentrations using a simple mathematical model based on the insulin half-life and the distribution space. In the case of highly purified monocomponent porcine insulin, maximum concentrations occurred after 30–60 min. The duration of insulin appearance was dose-dependent and the rate of appearance could be described by a bi-exponential function. It was linearly dose-dependent but the effect on glycaemia showed saturation kinetics. The action of the injected dose on the fasting glycaemia diminished when the appearance rate became 〈0.3 mU · kg-1 · min-1. Fractional dose recovery was between 70% and 90% and was not different between depot and regular insulin. Appearance kinetics were not significantly affected by the initial glycaemia. The model presented provides a means for quantitative characterization of different insulin preparations.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Pregnancy ; B-cell volume ; insulin ; Wistar rats ; streptozotocin administration ; islets ; DNA synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of pregnancy on pancreatic insulin content and relative B-cell volume has been studied in normoglycaemic Wistar rats treated with streptozotocin 14 days before mating. A single intravenous injection of streptozotocin (30 mg/kg body weight) caused a significant reduction of pancreatic insulin content and B-cell volume. The islet insulin content was 60% of control values. However, pregnancy-associated adaptation was preserved in these streptozotocin-treated animals. Plasma insulin levels, pancreatic insulin and B-cell volume were significantly enhanced compared with non-pregnant rats investigated on the same date. The incorporation of [3H]-thymidine into islets from pregnant rats (day 10.5) was higher than that in islets isolated from non-pregnant animals. After delivery insulin content and B-cell volume returned to pre-pregnant values. Also during a longer period after streptozotocin treatment (156 days), no measurable enhancement of B-cell volume and pancreatic insulin content was observed indicating the unresponsiveness of residual B cells to compensate spontaneously for the loss despite persisting normoglycaemia.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Monoclonal islet cell surface antibodies (mcICSA) ; anti-islet cell toxicity ; application in vivo ; pancreatic insulin content ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two monoclonal Beta-cell surface antibodies M10H6 und K14D10 were obtained by fusion of spleen cells of Balb/c mice with the myeloma cell line P30. The monoclonal antibody M10H6 was induced by immunization with rat insulinoma cells finally boostered with disintegrated rat islets, whereas the K14D10 was generated after immunization with porcine proinsulin. Both monoclonals belong to the IgG2A isotype and were screened with insulin-producing rat insulinoma cells by an indirect immunofluorescence test as well as by a cellular enzyme linked immunosorbent assay. In addition to the cell surface binding on living Beta cells the monoclonals react with islets on cryostat sections of rat pancreas. The anti-islet cytotoxic potential of these monoclonals was measured by 51Chromium-release in the presence of complement or Fc-receptor bearing leucocytes using 51Chromium-labelled rat islet cells as target. Both antibody secreting hybridomas were propagated in syngeneic mice resulting in high levels of islet cell surface antibodies in ascites and sera from the recipient. High anti-islet cytotoxicity was mediated by ascites fluid, but no mouse developed hyperglycaemia. Furthermore, the repeated injections of the monoclonals into rats did not exert a diabetogenic action and failed to reduce the pancreatic insulin content although the attraction of the K14D10 to the pancreatic islets in vivo could be demonstrated. We conclude that islet cell surface antibody-mediated Beta-cell lysis in vitro may not be relevant to Beta-cell destruction in vivo.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Artificial B-cell ; algorithm ; glucose-insulin relationship ; regression analysis ; insulin secretion ; insulin half-life ; human diabetes mellitus ; experimental diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin secretion rates after glucose loading were calculated from peripheral venous IRI concentrations considering half life and distribution space of exogenous insulin in normal men and dogs. The coefficients of multiple linear regression analysis between insulin secretion rates and plasma glucose (level and order and rate of change) were used as algorithm parameters in glucose-controlled insulin infusions. These were carried out in each dog based on individual estimations before the induction of diabetes but in the diabetic patients based on values derived from a group of normal subjects. Using this formula, nearly normal patterns of glucose and of insulin were observed in diabetic men and dogs under basal conditions and after IV glucose loading but not after meals. This algorithm enables selection of the parameters prospectively. The effect of a parameter combination depends on insulin sensitivity and it should be appropriately adapted. In the diabetic patients there was no predictable influence of the brittle or stable characteristics of the disease nor of insulin antibodies on the glucose curves obtained with glucose controlled insulin infusions.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Insulin resistance ; somatostatin infusion ; C-peptide ; insulin ; pancreatic glucagon ; growth hormone ; non-esterified fatty acids ; impaired glucose tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin resistance was studied in seven non-obese male subjects with impaired glucose tolerance and four healthy, age and body-weight matched male control subjects by means of a continuous intravenous infusion of somatostatin, glucose and insulin over 150 min. Glucose tolerance was evaluated by means of a 2-h glucose infusion test. Endogenous insulin (C-peptide), growth hormone, and glucagon secretion were suppressed by somatostatin in both groups. Steady-state plasma insulin and glucose levels were achieved between 90–135 min. Since similar steady-state levels of exogenous insulin were achieved, the resulting steady-state plasma glucose level provided a direct estimate of the ability of insulin to dispose of the infused glucose. The glucose levels were higher in subjects with impaired glucose tolerance with values of 14.6 ± 1.8 mmol/1 compared with 5.1 ± 1.2 mmol/1 in control subjects (p 〈 0.01), thus indicating insulin resistance. There was a direct correlation between the steady-state plasma glucose level and glucose tolerance suggesting that the degree of glucose intolerance is proportional to the degree of insulin resistance. These results revealed that decreased insulin sensitivity is found in non-obese subjects with impaired glucose tolerance.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Clinica Chimica Acta 142 (1984), S. 249-255 
    ISSN: 0009-8981
    Keywords: Endocrine pancreas ; Insulin ; Rapid RIA ; Transplantation
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Molecular and Cellular Endocrinology 32 (1983), S. 179-193 
    ISSN: 0303-7207
    Keywords: insulin biosynthesis and secretion ; insulin/glucagon ratio ; islet cell aggregation ; islet cells ; islet of Langerhans ; pseudo-islets
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Helgoland marine research 25 (1973), S. 446-451 
    ISSN: 1438-3888
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Cyclosporin A ; pancreatic insulin content ; glucose tolerance ; islet insulin content ; insulin secretion ; B-cell volume ; DNA-synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. This study investigated if and to what extent the acute toxic effect of Cyclosporin A on pancreatic Wistar rat B cells is reversible. After 2 weeks of treatment rats developed marked glucose intolerance accompanied by reduced pancreatic insulin content due to a loss of B cells, diminished islet DNA synthesis and decreased B-cell insulin content. Cyclosporin A had accumulated in the pancreas. Three weeks after withdrawal of Cyclosporin A, pancreatic tissue concentrations of Cyclosporin A were still 100 times larger than in serum. Glucose tolerance, however, had already improved, associated with an increase of B-cell insulin content and apparent islet replication, and the insulin response of isolated islets was reduced. Five weeks after the withdrawal of Cyclosporin A, glucose tolerance was normal, but pancreatic insulin content and relative B-cell volume were still diminished in comparison to vehicle-treated controls. Eight weeks after withdrawal, the morphometric parameters had also been normalized. The results suggest that the loss of pancreatic B cells is caused by a toxic destruction, possibly combined with an apparent decrease of replicatory activity. The acute toxic effects of Cyclosporin A in pancreatic B cells are stepwise reversible.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Tolbutamide ; insulin ; euglycaemic glucose clamp ; β cell ; Type 1 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We examined whether tolbutamide has any acute or short-term effects on insulin action in Type 1 (insulin-dependent) diabetes. A euglycaemic glucose clamp was performed in seven Type 1 diabetic patients without clinical insulin resistance by infusing glucose at a constant rate of 0.01 mmol·kg-1·min-1 for 3 h together with a simultaneous insulin infusion using an ‘artificial pancreas’. The insulin infusion rate required to maintain blood glucose at 6.7 mmol/l at a set low glucose infusion rate provides an index of insulin action in vivo. The euglycaemic clamp was performed on 3 separate days in the same patient: (1) in the basal state; (2) during simultaneous intravenous tolbutamide infusion of 0.5 g/h, and (3) after treatment with 2.5 g tolbutamide/day for 6 days in addition to insulin. The insulin infusion rate needed to maintain the set blood glucose level did not differ significantly between the three experimental conditions (1.2±0.2 versus 1.3±0.3 versus 1.2±0.3 U/h). Plasma glucagon, growth hormone, non-esterified fatty acid and glycerol levels did not differ between control or sulphonylurea treatment studies. The results suggest that tolbutamide does not exert any acute or short-term effects on insulin action in vivo in Type 1 diabetes. Our results do not provide support for the idea that this agent is a clinically useful adjunct to insulin in such patients.
    Type of Medium: Electronic Resource
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