Report of the third workshop of the EASD study group on artificial insulin delivery systems, pancreas and islet transplantation (AIDSPIT). 5-7 February 1984, Igls, Austria.
Explore the source record for details and available documents.
Cyclosporins↗
Biomedical subjects
E F Pfeiffer
Publications and source records attributed to E F Pfeiffer.
Effect of continuous and oscillatory portal vein insulin infusion upon glucose-induced insulin release in rats.
The present study was designed to determine the effect of low dose continuous and oscillatory intraportal insulin infusions upon subsequent glucose-induced insulin release. In overnight-fasted and anesthetized rats with indwelling catheters in the jugular vein, carotid artery, and mesenteric vein insulin was infused intraportally for 3 h via the mesenteric vein catheter at a continuous rate of 45 microU/kg X min, or the same amount of insulin was administered at alternating high (72 microU/kg X min) and low infusion rates (18 microU/kg X min), respectively, in 2-, 4-, 8-, and 16-min cycles (oscillatory infusions). Another group received a continuous infusion of saline. Glucose (0.4 g/kg) was given i.v. 30 min after the end of the insulin or saline infusion. During the 3-h infusion of insulin or saline the peripheral glucose level remained unchanged in all groups. In response to the i.v. glucose load peripheral arterial plasma insulin levels were significantly elevated after preceding oscillatory infusions compared to the continuous insulin infusion. As compared to the group receiving saline the glucose-induced insulin response after continuous insulin infusion was significantly reduced. The plasma glucose responses were not different except for inexplicably elevated glucose levels in the 4-min cycle group. No difference was observed for plasma glucagon levels in all groups. The present data demonstrate an augmented responsiveness of the beta-cell to glucose after a preceding oscillatory infusion of insulin and an impaired responsiveness to glucose after continuous insulin infusion. This indicates that an oscillatory insulin release might be of importance for an adequate regulation of beta-cell function.
Animals↗
Studies on the pathogenesis of the dawn phenomenon in insulin-dependent diabetic patients.
To assess the role of hormonal factors in the pathogenesis of the dawn phenomenon, nocturnal (9:00 PM to 9 AM) concentrations of blood glucose, free insulin, and counterregulatory hormones were determined in eight insulin-dependent diabetic patients under feedback-controlled and continuous insulin infusions after previous blood glucose normalization. Under feedback control, mean insulin requirements, necessary for maintenance of euglycemia rose significantly in the early morning (11:00 PM to 3 AM: 8.4 +/- 1.4; 5 AM to 9 AM: 12.6 +/- 1.5 mU/kg/h; P less than 0.01). Mean free-insulin concentrations did not increase simultaneously. Correspondingly, mean insulin-clearance rates under continuous insulin infusion were higher in the morning (11:00 AM to 3 AM: 359 +/- 58; 5 AM to 9 AM: 459 +/- 72 mL/min/m2; P less than 0.05). Increases of insulin clearance rates were most marked (greater than 15%) in patients whose blood glucose rose during continuous insulin administration. Glucagon and norepinephrine concentrations were stable throughout both parts of the study. Cortisol and growth hormone exhibited the known nocturnal rhythms. Epinephrine levels were at the lower limit of detection at night and rose to normal basal concentrations at 9:00 AM. We conclude that increases of insulin clearance rates may be an important factor for the development of the dawn phenomenon while the role of most counter-regulatory hormones is still uncertain.
Adult↗
Endogenous opioids modulate the effect of cholecystokinin on insulin release in dogs.
Recently we have demonstrated in dogs and man that endogenous opioids participate in the regulation of pancreatic endocrine function following the ingestion of a meal. Since intestinal hormones such as cholecystokinin (CCK) are also released by the presence of nutrients in the gastrointestinal tract and participate in the postprandial stimulation of pancreatic endocrine function, an interaction between CCK and endogenous opioids seems possible. The present study was designed to examine this further. In a group of 8 conscious dogs the octapeptide of CCK was infused intravenously in its sulfated (CCK-8S) or nonsulfated (CCK-8NS) form and in addition the tetrapeptide of CCK (CCK-4) was given at increasing infusion rates of 50, 200 and 500 pmol/kg . h, respectively. The experiments were performed during a background infusion of saline to assess the effect on basal insulin and during a background infusion of glucose (0.2 g/min) to determine the effects on stimulated insulin release. The effect of endogenous opioids was examined by addition of the opiate-receptor antagonist naloxone. The studies demonstrate that in the basal state CCK-8S has no stimulatory effect on insulin secretion unless naloxone is added indicating that endogenous opioids help to prevent insulin secretion in the absence of elevated glucose levels. During i.v. glucose naloxone reduced the stimulatory effect of CCK-8S at 50 and 200 pmol/kg . h and that of CCK-4 at 50 pmol/kg . h. Infusion of CCK-8S and CCK-4 at 500 pmol/kg . h had no effect on glucose-stimulated insulin levels, however, the addition of naloxone elicited a significant stimulatory effect. These data demonstrate stimulatory as well as inhibitory effects of endogenous opioids depending on the dose of CCK-8 and -4. CCK-8NS reduced glucose-stimulated insulin release already at the lowest dose of 50 pmol/kg . h. This was reversed to a stimulatory effect with the addition of naloxone. These data demonstrate that the interaction between CCK-8 and -4 and endogenous opioids on prestimulated insulin secretion is much more dependent on the dose of CCK - low doses induce stimulatory and high doses inhibitory mechanisms via endogenous opioids. In view of previous in vitro and in vivo studies with exogenously infused opiate-active compounds it might be speculated that increasing doses of CCK elicit a parellel increase in the release of endogenous opioids which might be responsible for some but certainly not all of the effects observed recently for the action of naloxone in the post-prandial state.
Animals↗
Modulation of acetylcholine-induced secretion of gastric bombesin-like immunoreactivity by cholinergic and histamine H2-receptors, somatostatin and intragastric pH.
Recently we have shown the release of bombesin-like immunoreactivity (BLI) from the isolated perfused rat stomach. In these experiments we have shown that BLI secretion is stimulated by acetylcholine. Gastric inhibitory peptide (GIP) exerts an inhibitory effect which is dependent on the intraluminal pH. The present study was designed to examine further the exact cholinergic mechanisms and to study the interaction between cholinergic and histaminergic mechanisms as well as the effect of the intraluminal pH. Acetylcholine elicited a dose-dependent increase in BLI and gastrin secretion (10(-6) M and 2 X 10(-6)M), whereas somatostatin release was suppressed at luminal pH 7. Blockade of muscarinic cholinergic receptors by atropine (10(-5)M) and nicotinic cholinergic receptors by hexamethonium (10(-5) M) abolished the effect of acetylcholine on all three peptides. Reduction of the intraluminal pH to 2 also abolished acetylcholine-induced stimulation of BLI and gastrin secretion and the inhibition of somatostatin secretion. Changes of intraluminal pH per se had no effect on the secretion of either peptide. Somatostatin (10(-7) M) reduced both BLI and gastrin secretion during stimulation with acetylcholine. The addition of the H2-receptor antagonist cimetidine (10(-5) M) abolished the effect of both doses of acetylcholine on BLI and somatostatin secretion and also the effect of the lower dose of acetylcholine (10(-6) M) on gastrin secretion during luminal pH 7. At luminal pH 2 cimetidine did not alter BLI and somatostatin secretion in response to acetylcholine, however, gastrin release was augmented in the presence of cimetidine. These data demonstrate that the effect of acetylcholine on BLI, gastrin, and somatostatin secretion is mediated by muscarinic and nicotinic cholinergic receptors and also by histamine H2-receptors. Somatostatin inhibits cholinergically induced BLI secretion. The cholinergic effects on BLI, somatostatin and gastrin secretion are abolished during an acidic intragastric pH. In this isolated perfused rat stomach model the inhibitory effect of intraluminal acid on gastrin secretion is, at least in part, mediated by H2-receptors. This suggests that the secretion of bombesin, a potential peptidergic neurotransmitter is modulated by neural, endocrine and local tissue factors and also by alterations of intragastric pH.
Acetylcholine↗
Alpha-adrenergic effects on insulin release from isolated pancreatic rat islets are influenced by alpha-glucosidase.
The modification of isolated pancreatic rat islets by pretreatment with alpha-glucosidase abolished the stimulatory action of phentolamine but not changed glucose induced insulin release. In modified islets the inhibitory effect of epinephrine was only slightly changed. The data indicated that alpha-adrenergic receptors may be selectively damaged by alpha-glucosidase.
Animals↗
Abnormal growth hormone levels in insulin-dependent diabetic patients under continuous subcutaneous insulin infusion and intensified conventional treatment.
The present study was developed to assess the influence of prolonged blood glucose near normalization, achieved by means of continuous sc insulin infusion (CSII) or intensified conventional therapy (ICT) upon growth hormone (GH) secretion in insulin-dependent diabetes (IDD). Sixteen IDD patients (8 CSII-treated for 3-20 months and 8 under ICT) and 8 healthy control subjects were connected for 24 h to a newly developed, battery-powered glucose monitor. Diabetic patients received their usual food intake and insulin doses. During the second hour after meals moderate exercise, walking at 1.5 km/h, was performed by all subjects. Blood samples for insulin and GH determination were taken before and 60, 120 and 180 min after meal ingestion. Despite a similar degree of previous blood regulation, near normal glucose levels were attained only by the CSII group. Both ICT and CSII patients presented a marked postprandial hyperinsulinaemia. Abnormal GH levels were consistently registered in 4 CSII and 6 ICT patients 120 min after meal initiation. In consequence, both groups showed significantly elevated mean diurnal GH levels (controls: 1.1 +/- 0.3, ICT: 5.2 +/- 0.9, CSII: 4.1 +/- 1.1 ng/ml; P less than 0.05). According to these results, the pathologic GH secretion found in diabetic subjects is not fully normalized by tight control of blood glucose values.
Adolescent↗
[The artificial endocrine pancreas and insulin pumps: past, present and future].
Explore the source record for details and available documents.
Animals↗
Increased hepatic microsomal T3 production in vitro induced by insulin administration in rats in vivo.
Rats were treated with insulin infusion over 12 h with or without addition of cycloheximide and compared with controls. T4 to T3 deiodination in microsomal liver fraction was measured. Insulin treatment led to an increase in T3 production, whereas this effect was blunted by the inhibition of protein synthesis by cycloheximide. Neither serum concentrations of T4 nor the liver content of non-protein-bound sulph-hydryl groups explained the alterations in T3 production. It is strongly suggested that insulin directly acts on T4-5'-monodeiodination by stimulating de novo synthesis of protein.
Animals↗
The influence of glucose and insulin infusion on in vitro T4 Monodeiodination in rat liver microsomes.
Explore the source record for details and available documents.
Animals↗
Radioimmunoassay of somatostatin in human plasma.
A radioimmunoassay procedure for determination of somatostatin immunoactivity in human plasma is described. Labelling of tyrosine-1-somatostatin is performed by chloramine T. Specific activity of the tracer is 1.34 mol iodine for 1 mol of somatostatin. The immunoreactivity is 85%. Antisera are produced in rabbits at a titre of 179 X 10(-12) mol somatostatin per ml antiserum. Human plasma is extracted by n-butanol/2 mol/l acetic acid. Recovery rate is 85-105%. The intra-assay CV varies from 12% to 1.7%, the inter-assay CV from 16% to 7.5%, depending on the concentration of somatostatin.
Animals↗
Somatostatinoma syndrome. Clinical, morphological and metabolic features and therapeutic aspects.
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.
Adenoma, Islet Cell↗
[Optimal delivery of insulin. Future aspects].
Explore the source record for details and available documents.
Diabetes Mellitus↗
Nucleated blood cells both bind and internalize insulin.
Explore the source record for details and available documents.
Animals↗
Effects of synthetic rat C-peptide in normal and diabetic rats.
The effects of synthetic rat C-peptide 1 and C-peptide 2 on plasma insulin and blood glucose concentrations in the rat were studied. Infusion of rat C-peptide (500 micrograms X h-1 X kg-1) diminished glucose induced increase of plasma insulin by 56% (15.2 +/- 0.9 versus 6.6 +/- 0.6 ng/ml, p less than 0.01, mean +/- SEM). Somatostatin infused at a rate of 50 micrograms X h-1 X kg-1 body weight inhibited glucose-induced insulin secretion by 33%. In the presence of a mixture of both C-peptides or somatostatin, blood glucose after intravenous glucose was higher than in the control experiments. In alloxan-diabetic rats, C-peptide (160 micrograms/kg) significantly increased and prolonged the hypoglycaemic effect of exogenous insulin. It is suggested that C-peptide may not be a biologically inert substance.
Animals↗
Modulation of post-prandial insulin release by ingested opiate-like substances in dogs.
Explore the source record for details and available documents.
Animals↗
Cholinergic mechanisms in intestinal phase insulin secretion in rats.
The present study was designed to examine the role of neural cholinergic mechanisms in intestinal phase insulin secretion during increasing intraduodenal instillation rates of the test meals. In groups of 12 anesthetized rats arterial insulin levels rose significantly in relation to the increase of the rate at which the liver extract/sucrose was instilled intraduodenally (0.15, 0.5 and 1.5 ml/min). The injection of atropine (10 micrograms/kg) 5 min prior to the intraduodenal infusion of the test meals abolished this rate-dependent augmentation of insulin levels completely. Similarly, no effect of increasing intraduodenal infusion rates of the meal was observed in islet-transplanted rats. These data demonstrate that neural - at least in part muscarinic cholinergic - mechanisms participate in intestinal phase insulin secretion of rats supporting previous observations about the importance of neural factors in the regulation of postprandial insulin release.
Acetylcholine↗