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  • Cyclosporin A  (1)
  • Tolbutamide  (1)
  • Wistar rats  (1)
  • 1
    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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  • 2
    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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  • 3
    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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