B cell response to portal or systemic endocrine graft drainage in heterotopic pancreas transplantation in the rat.
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Biomedical subjects
Publications and source records attributed to W Beischer.
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A case of somatostatinoma syndrome in a 30-year-old woman is presented. Basal levels of growth hormone and of pancreatic and gastric hormones were reduced and the response of growth hormone, insulin and C-peptide to stimuli such as arginine, glucose, glibenclamide and calcium was virtually abolished. Similarly, gastric acid secretion, pancreatic exocrine function and intestinal absorption were significantly reduced. On the other hand, basal and stimulated levels of adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) were within the normal range. Plasma somatostatin-like immunoreactivity was increased to 600-2,000 pg/ml (normal: 88-140 pg/ml). Immunocytochemical studies demonstrated the presence of somatostatin immunoreactive material in the primary tumour in the head of the pancreas and in the liver metastases. In spite of two courses of chemotherapy with streptozotocin and 5-fluorouracil the patient died due to liver failure 5 months after the first admission to hospital.
The insulin secretory capacity was examined in diabetic children at the time of partial clinical remission during which their condition could be managed with low insulin therapy (less than 0.5 U insulin/kg body weight) and no urinary glucose excretion. The extent of the residual beta cell function in 26 children was assessed either by an i.v. arginine test, a combined i.v. glucose-i.v. arginine test, a combined i.v. tolbutamide-i.v. arginine test, or a combined oral glucose-i.v. arginine test determining the C-peptide response by calculating the area under the curve above baseline levels. Two of the children were tested repeatedly. Under the above conditions i.v. glucose and i.v. tolbutamide did not release C-peptide in diabetic children. In contrast, C-peptide secretion during arginine infusion following i.v. glucose or i.v. tolbutamide was significantly enhanced compared to the C-peptide secretion observed during arginine infusion alone. The C-peptide response to oral glucose was sluggish with no effect on the following arginine infusion. The results indicate that during remission in juvenile onset diabetes i.v. glucose and i.v. tolbutamide without themselves being an appropriate signal for C-peptide release amplify the response to a subsequent arginine infusion under appropriate conditions.
30 patients undergoing knee-operations were randomized in two groups. 15 patients were operated on under neuroleptanalgesia. Piritramid was given postoperatively. The other group of patients was operated under epidural analgesia, postoperatively they were kept painfree by continuous infusion of 0.2% bupivacaine via an epidural catheter at a rate of 0.2 ml/kg.h over a period of 24 h. The aim of our study was to find out if continuous epidural anaesthesia in contrast to neurolept analgesia was able to prevent the hormoneal and metabolic response to these painful operations. Plasma glucose, insulin, C-peptidee, glucagon, cortisol, human growth hormon, and beta-hydroxybutyric acid were measured before commencing anaesthesia (point 0), after induction (point N), at the end of operation (point Op) and 1, 2, 4, 6, 12 and 24 h postoperatively (point 1, 2, 4, 6, 12 and 24). In both groups of patients an intravenous glucose tolerance test was carried out after 24 h. There were significant differences between the two groups in plasma glucose, insulin, C-peptid and cortisol, indicating that the stress response can be mitigated by continuous epidural anaesthesia. These differences however were only found in the first few postoperative hours. After a period of 24 h there were no differences at all, the metabolic alterations as indicated by the pathological glucose tolerance test, were the same in both groups, independent of the anaesthetic method used.
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Chemistry, biochemistry and physiology of proinsulin and C-peptide are summarized. A short characterization of the radioimmunological methods for measuring C-peptide and proinsulin follows. The determination of C-peptide and proinsulin which was mainly carried out in serum or plasma essentially improved our knowledge about the function of the beta-cells in the islets of Langerhans in healthy subjects and diabetic patients. The paper reports on the occurrence and the course of C-peptide and proinsulin in healthy subjects and in diabetics of type I and II.
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Increased HbA1c concentrations in diabetic patients indicate retrospectively a poor metabolic control during the preceding 2-3 months. In the present study attempts have been made to use the HbA1c concentration at the time of diagnosis as an indicator of the duration of the remission phase in 23 juvenile diabetic children. The regression analysis revealed a significant negative correlation between the initial HbA1c concentrations and the duration of the remission phase defined as no glucose excretion, an insulin requirement of less than 0.5 U/kg/day and detectable serum C-peptide concentration (r =- 0.84, p < 0.001). The results suggest that the initial HbA1c concentration may serve as a useful indicator to predict the duration of the remission phase in juvenile-onset diabetic patients.
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In 35 children with long-standing diabetes mellitus, a significant correlation was found between the hemoglobin A1c (HbA1c)--and the 24-hour urinary glucose excretion. By contrast, 11 newly diagnosed diabetic children had grossly elevated HbA1c-concentrations, but no correlations could be established between the levels of HbA1c and the duration of symptoms, blood glucose, glycosuria, ketonuria and the acid--base status. However, HbA1c and C-peptide were significantly correlated. The elevated HbA1c-concentrations decreased towards normal in all of these 11 children after 2--3 months following adequate therapy. The results suggest that the determination of HbA1c may serve as a valuable metabolic control index in children with long-standing diabetes mellitus, but adds little information in newly diagnosed patients. For the individual diabetic child during the early treatment period, HbA1c may be the index of choice for adequacy of metabolic control.
Application of the artificial endocrine pancreas in 12 patients undergoing total duodenopancreatectomy and 3 diabetics in whom different operations were performed proved to be safe for the patients with respect to blood glucose control and prevention of ketosis. In the postoperative period, essentially normal blood glucose values were obtained despite high caloric parenteral nutrition.
The influence of different control modes for insulin infusion with an artificial beta cell was examined in 41 insulin-dependent diabetics. In 21 Patients, oral glucose tolerance tests were performed with control modes characterized either by low dynamic and high static gain (type I, 10 patients) or high dynamic and low static gain (type III, 11 patients). The change from type I to type III control mode effected an increase of initial insulin infusion rates (91 +/- 59 to 313 +/- 81 mU/min 10-20 min after glucose ingestion) and a decrease of infusion rates during the following phase of the 3-hour observation period (28.2 +/- 4.2 to 18.1 +/- 2.8 U) in patients whose blood glucose curves were completely normalized. Suppression of plasma glucagon levels, observed in 5 healthy control subjects, was not fully restored to normal in these patients. In another 20 insulin-dependent diabetics, daily insulin requirements form the artificial beta cell were determined by employing two control modes (types II and III) comparable in static control but different in dynamic control. Gain of dynamic control, especially in the range of falling glucose levels, was higher in type III control mode (15 patients) than in type II mode (5 patients). These insulin requirements were compared to the insulin doses necessary for subcutaneous treatment. While intravenous insulin requirements were much higher when type II control mode was employed (78.2 +/- 10.2%), during application of type III mode, intravenous insulin requirements were only 10.8 +/- 5.5% higher than subcutaneous doses. We conclude from these data that early increases in insulin infusion rates followed by a rapid decrease seem to reduce insulin requirements after glucose ingestion. A high-gain dynamic control is the basis for this insulin infusion profile.
Insulin self-inhibition is still a controversial subject. The majority of data is in favour of an inhibition; however, whether this mechanism is of physiologic relevance in the regulation of insulin secretion is open to discussion. We examined the effect of exogenous insulin on beta cell secretion in 16 volunteers, including 3 who were overweight. Blood glucose (BG) was clamped by means of the dextrose infusion unit of the artificial beta cell, and the secretion of the pancreatic beta cell was monitored by immunomeasureable C-peptide (IMCP) before, during, and after infusion of insulin. The subjects were divided into 3 experimental groups. The inhibition of the basal insulin secretion was examined in group I by clamping BG at the fasting level. The inhibition of the glucose-stimulated insulin secretion was examined in group II by clamping BG at a raised level. The stimulation of insulin secretion by glucose during insulin infusion was examined in group III by stepwise BG rises from the fasting level. An inhibition of the basal insulin secretion was observed in all volunteers examined according to the protocol for group I (n = 9, including 3 overweight volunteers). The lowest insulin infusion rate applied was 1.75 U/h. An inhibition occurred at this low infusion rate corresponding to 44 mu U immunomeasurable insulin (IMI) per ml of serum. However the inhibition was impaired in the overweight participants, who, in addition, were the only ones showing a rebound rise of IMCP after stopping the insulin infusion. An inhibiting effect of exogenous insulin appeared as likely in only 1 of 5 participants examined according to the protocol for group II. Sudden rises of BG abolished the inhibition, while a total or partial inhibition was found at a constantly raised BG level in both participants examined according to protocol III. We conclude that exogenous insulin inhibits beta cell secretion, depending on the BG level, the mode of glucose stimulation, and the time relation between glucose and insulin application. Physiologically occuring IMI levels in peripheral serum were sufficient to cause an inhibition. A disturbance of the negative feedback inhibition of insulin should be discussed as a pathogenetic factor of adipositas.
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