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  • 1
    ISSN: 1432-0428
    Keywords: Isolated islets ; tissue culture ; insulin release ; cyclic AMP ; gastric inhibitory polypeptide ; perifusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several insulinotropic hormones have been shown to increase the level of cyclic AMP in isolated islets. This study was performed to investigate whether gastric inhibitory polypeptide (glucose-dependent insulin-releasing polypeptide) has a similar effect, in particular at concentrations close to the physiological level in blood. Collagenase isolated rat islets were maintained for 24 h in tissue culture (medium 199) and then incubated for 30 min for measurement of insulin release and cyclic AMP content. Glucose-induced (16.7 mmol/ 1) insulin release was enhanced by gastric inhibitory polypeptide 1–100 ng/ml (0.196–19.6 nmol/l) in a dose-related fashion. The cyclic AMP content was enhanced only by 100 ng/ ml. However, when 0.1 mmol/l of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine was present, even 1 ng/ ml of gastric inhibitory polypeptide increased both cyclic AMP content and insulin release. Such a concentration of the hormone can be measured in human blood after a meal. In contrast, in freshly isolated islets no effect of the hormone on glucose-induced insulin release or cyclic AMP content could be detected for concentrations ranging from 1 to 100 ng/ml. These findings demonstrate that the hormone sensitivity of isolated islets is markedly enhanced by short-term maintenance in tissue culture. The results suggest that an increase in cyclic AMP is seen in response to gastric inhibitory polypeptide and may be causally related to the insulinotropic effect of the hormone.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Glucagon-like peptide-1 ; glucagon-like peptide-2 ; insulin release ; glucose dependency ; isolated islets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucagon-like peptide-1 and glucagon-like peptide-2 are encoded by the m-RNA of pancreatic preproglucagon. They show high conservation in different species and substantial sequence homology to glucagon. Because no definite biological activity of these peptides has been reported, we investigated the effect of synthetic C-terminally amidated glucagon-like peptide-1 [1–36] and synthetic human glucagon-like peptide-2 [1–34] with a free C-terminus on insulin release from isolated precultured rat pancreatic islets in the presence of glucose. Glucagon-like peptide-1 stimulates insulin release at 10 and 16.7 mmol/l glucose in a dose-dependent manner. Significant stimulation starts at 2.5 nmol/l in the presence of 10 mmol/l glucose and near maximal release is observed at 250 nmol/l, with approximately 100% increase over basal at both glucose concentrations. The peptide reaches 63% of the maximal stimulatory effect of glucagon. No stimulation occurs in the presence of 2.8 mmol/l glucose. Glucagon-like peptide-2 has no effect on insulin secretion at any glucose concentration tested. It is concluded that glucagon-like peptide-1, in contrast to glucagon-like peptide-2, exhibits a glucose-dependent insulinotropic action on isolated rat pancreatic islets similar to that of glucagon and gastric inhibitory polypeptide.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Streptozotocin diabetes ; rats ; low carbohydrate-high protein diet ; low carbohydrate-high ; fat diet ; blood glucose ; urinary glucose ; serum lipids ; ketone bodies ; serum insulin ; pancreatic insulin ; pancreatic glucagon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Groups of diabetic rats (65 mg/kg streptozotocin SC) were fed ad lib on three different dietary regimens for 43 weeks: a standard control diet (68% of calories as carbohydrate, 20% as protein, and 12% as fat), a low carbohydrate high protein diet (6% carbohydrate, 63% protein, 31% fat) or a low carbohydrate-high fat diet (5% carbohydrate, 75% fat, 20% protein). The high fat diet resulted in a fall of blood glucose from 700 to 350 mg/100 ml. Rats fed the high protein diet showed a similar initial decrease in blood glucose concentration, and a further improvement was evident from the 28th week on. After 43 weeks blood glucose levels were below 180 mg/100 ml and glycosuria below 100 mg/24 h in all rats fed the high protein diet. When rats exhibiting blood glucose levels below 180 mg/dl were transferred temporarily to standard diet blood glucose levels increased and marked glycosuria was observed. Rats on the standard diet maintained blood glucose concentrations greater than 500 mg/100 ml and glycosuria of about 16 g/24 h throughout the experiment. The pancreatic insulin content at death of rats fed the standard diet or the high fat diet was 1% of normal rats, whereas the values for the rats on the high protein diet were increased to 9%. Animals fed the low carbohydrate diets showed greater weight gain. In the high fat diet group there was a marked rise after 43 weeks in plasma triglycerides, free fatty acids, 3-hydroxybutyrate and acetoacetate in the plasma. Urea excretion was raised in the animals on the high protein diet. Thus, treatment with low carbohydrate diets for 10 months regardless of fat and protein content markedly improved the diabetic state of rats.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Preabsorptive insulin secretion ; cephalic phase insulin response ; taste reactivity ; B-cell denervation ; hepatic islet transplantation ; brain stem ; diencephalon ; hypothalamus ; nucleus of solitary tract ; glucose tolerance ; dietary obesity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using chronically catheterized, freely moving male Wistar rats, we have shown that the sweet taste of a saccharin solution reliably triggers a rapid cephalic phase insulin response (CPIR), in the absence of any significant change of glycemia. To establish the neural mediation of this reflex response we used rats that were cured from streptozotocin diabetes by intrahepatic islet-transplantation as a denervated B-cell preparation. The complete lack of any saccharin-induced CPIR in these rats suggests that it is indeed mediated by the peripheral autonomic nervous system, and that the insulin-stimulating gastrointestinal hormones are not involved in this response. It was further found that this reflex insulin secretion is not easily extinguishable and thus might have an unconditioned component. To investigate the central neural pathways involved in this reflex response we used both electrophysiological methods in anesthetized and semi-micro CNS manipulations in freely moving rats. On the basis of our preliminary results, and several reports, using the decerebrate rat preparation for measuring behavioral or saliva secretory oral taste reactivity, it appears that CPIR might be organized at the brain stem/midbrain level, receiving strong modulatory influences from the diencephalon. But much further work has to be done to establish the central nervous circuitry. Finally, in two experiments, aiming at the question of how important and physiologically relevant the CPIR might be, we found that, on one hand, its lack can result in pathological oral glucose tolerance and on the other hand its exaggeration might contribute to the behavioral reaction to highly palatable sweet food and the resulting development of dietary obesity.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Pancreas transplantation ; Insulin secretion ; C-peptide ; Systemic venous drainage ; Insulin metabolic clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma glucose, immunoreactive insulin and C-peptide concentrations were compared in nine pancreas-kidney-transplanted patients (systemic venous drainage) and in ten non-diabetic kidney-transplanted patients with similar kidney function. In the basal state, C-peptide (insulin secretion) was similar, but immunoreactive insulin was higher and glucose concentrations were slightly, but significantly lower in pancreas-transplanted patients. After 50 g oral glucose, the plasma glucose and IR-insulin profiles were similar in both groups. The circumvention of first-pass hepatic insulin extraction (decreased endogenous insulin clearance) was compensated for by a significant reduction in insulin secretion (C-peptide; p=0.036). In conclusion, hyperinsulinaemia in pancreas-transplanted patients with systemic venous drainage is significant only in the basal state. Insulin delivered into the portal and peripheral circulation, when leading to similar insulin profiles, maintains comparable degrees of glucose tolerance.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Cyclosporin A ; B cell changes ; pancreatic insulin content ; insulin levels ; hyperglycaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cyclosporin A (50 mg/kg orally for 7 days) produced severe degranulation and hydropic degeneration of islet B cells in rats. These changes were accompanied by hyperglycaemia and hypoinsulinaemia, while the pancreatic insulin content decreased by 75%.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 68 (1990), S. 306-312 
    ISSN: 1432-1440
    Keywords: Near-normoglycemia ; Pancreas transplantation ; Artificial pancreas ; Insulin pump treatment ; Secondary complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In diabetic patients (near-)normoglycemic control of blood glucose can only rarely be achieved by conventional insulin treatment. Novel strategies for this goal include transplantation of pancreatic tissue (whole organ, segment or isolated islets), the artificial pancreas with continuous blood glucose monitoring, insulin pump treatment and the intensified conventional treatment both of the latter including self-measurement of blood glucose and self-adaptation of the insulin dosis. The results of pancreas transplantation in recent years have shown a marked improvement, the one-year survival rate of a functioning organ is in the range of 50–70%. Due to the lifelong immunosuppression pancreas transplantation should be considered in diabetic patients who need a kidney transplantation and for this reason already require immunosuppression. In spite of encouraging results in animals islet transplantation in humans has been disappointing to date. The artificial pancreas at present cannot be used for long-term treatment mainly due to the problems of the glucose sensor. The application of insulin pump treatment without continuous monitoring of blood glucose (open loop) and intensified conventional treatment both can lead to improved glycemic control in spite of a more flexible life style. Only this way of treatment made it possible to perform randomized prospective studies in diabetic patients on the effect of (near-)normoglycemic control on secondary complications. The first results show a tendency towards a positive effect on mild to moderate diabetic retinopathy over 2 years. Thus, every juvenile diabetic patient should be informed about these possibilities of treatment. To definitely answer this question a large randomized prospective controlled trial including 1400 patients (Diabetes Control and Complications Trial, DCCT trial) is currently performed over 5 years both with respect to the influence of near-normoglycemia on existing secondary complications as also on their prevention.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1440
    Keywords: Pancreas transplantation ; Insulin secretion ; Pancreatic hormones ; Gastrointestinal peptide hormones ; Rènal elimination (clearance) ; Systemic venous pancreas drainage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The secretion of pancreatic and gastrointestinal hormones in the basal state and after nutrient stimuli (50 g glucose, 50 g protein, or 30 g triglyceride administered on separate occasions) was assessed in ten previously type-1-diabetic patients after successful combined kidney and pancreas transplantation (systemic venous drainage). Fasting values were compared to matched non-diabetic kidney-transplanted patients and related to kidney function (endogenous creatinine clearance) and to the type and dosage of immunosuppressive medication. In the fasting state, only IR insulin concentrations were higher in pancreas-kidney-transplanted patients (by 88%; P=0.001) than in the kidney graft recipients. There were significant inverse correlations of plasma C-peptide, GIP, and gastrin immunoreactivity to endogenous creatinine clearance (kidney function). In response to nutrients, insulin secretion (IR insulin, C-peptide) was significantly stimulated by glucose, and — to a lesser degree — also by protein. Pancreatic glucagon was suppressed by glucose and stimulated by protein ingestion. GIP was raised after glucose and triglyceride more than after protein (P=0.0003). GLP-1 immunoreactivity was stimulated by all nutrients, with a tendency towards higher responses to protein and fat (P=0.06). Gastrin was mainly raised by protein. In conclusion, the overall pattern of pancreatic and gastrointestinal hormone release is normal in patients after combined pancreas-kidney-transplantation, but there are some peculiarities due to (a) systemic venous drainage of the pancreas graft (elevated fasting IR insulin) and (b) impaired kidney function (negative correlation of fasting plasma values to endogenous creatinine clearance for C-peptide, GIP, and gastrin). The plasma levels of these important regulatory peptides and their responses to nutrient stimulation are compatible with and may contribute to the well-preserved endocrine function of the pancreatic grafts (normal or slightly impaired glucose tolerance, preserved incretin effect).
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Intensive care medicine 26 (2000), S. 572-576 
    ISSN: 1432-1238
    Keywords: Key words Pericardiocentesis ; Cardiac tamponade ; Recurrent pericardial effusion ; Repeat pericardiocentesis ; Risk of pericardiocentesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To evaluate the risk and effectiveness of pericardiocentesis in primary and repeat cardiac tamponade Design: Retrospective analysis. Setting: Intensive care unit in a medical university hospital. Patients: Sixty-three consecutively admitted patients with cardiac tamponade. Interventions: In all patients pericardiocentesis was performed via the subxiphoid pathway after echocardiographic detection of the pericardial effusion. Measurements and results: There was no adverse event in patients undergoing primary pericardiocentesis, which was sufficient to resolve pericardial effusion in 51 of 63 patients (81 %). However, repeat pericardiocentesis necessitated by the recurrence of symptomatic pericardial effusion yielded suboptimal results in 10 of 12 patients (83 %). Conclusion: Pericardiocentesis is the treatment of choice for primary symptomatic pericardial effusion. In recurrent pericardial effusion surgical approaches appear to be preferable.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1433-8580
    Keywords: Streptozotocin ; Pancreatic islets ; B cells ; Low carbohydrate diet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of different diets on the endocrine pancreas of streptozotocin-diabetic rats were investigated by morphometry. Three dietary regimens were used over a period of 43 weeks: standard diet (SD), low carbohydrate-high protein diet (LC-HP), and low carbohydrate-high fat diet (LC-HF). Nondiabetic controls received standard diet. Volume density of the total endocrine tissue was significantly reduced in streptozotocin-diabetic rats kept on standard diet as compared to control rats. This reduction of endocrine tissue was significantly less in rats kept on LC-HP diet, whereas diabetic rats kept on LC-HF did not differ from diabetic rats on standard diet. In streptozotocin-diabetic rats volume density of B cells was drastically reduced, whereas volume densities of A, D and PP cells did not differ from nondiabetic controls. This decrease of B cells was partially prevented by LC-HP diet, but not by LC-HF diet. In nondiabetic control rats as in diabetic rats on standard diet most of the islets of Langerhans sized 500–6000 µm2. In contrast, diabetic rats on LC-HP diet revealed more endocrine tissue sized from 50 to 560 µm2 consisting of two to four endocrine cells, single cells, and small islets. The results suggest that LC-HP diet may initiate reparation processes in the endocrine pancreas of streptozotocin-diabetic rats.
    Type of Medium: Electronic Resource
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