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  • 1
    ISSN: 1432-1440
    Keywords: Thymus ; Cryptocrine signaling ; Neuroen docrine self-antigens ; Molecular evolution ; Developmental biology ; T cell tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Both during phylogeny and ontogeny the thymus appears as a nodal point between the two major systems of cell-to-cell signaling, the neuroendocrine and immune systems. This review presents the experimental observations which support a dual role in T cell selection played by the thymic repertoire of neuroendocrine polypeptide precursors. Through the mode of cryptocrine intercellular signaling thymic neuroendocrine-related precursors synthesized in thymic epithelial cells have been shown to influence the early steps in T cell differentiation. In addition, thymic neuroendocrine-related polypeptides are a source of self-antigens which are presented by the major histocompatibility system of the thymic epithelium. Preliminary data also suggest that the intrathymic T cell education to neuroendocrine self-antigens is not strictly superimposible to the antigen presentation by dedicated presenting cells. Insulin-like growth factor-II (IGF-II) was identified as one dominant member of the insulin family expressed by thymic epithelial and nurse cells. The intrathymic presentation of IGF-II or IGF-II derived self-antigens is under current investigation. If further confirmed, the central tolerogenic properties of IGF-II could be considered in the elaboration of a strategy for an efficient and safe prevention of insulin-dependent diabetes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Idiopathic haemochromatosis ; diabetes ; glucagon secretion ; arginine infusion ; oral glucose tolerance test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present investigation was to determine in patients with idiopathic haemochromatosis whether diabetes is of the primary type or secondary to pancreatic injury due to iron deposition. For this purpose, plasma glucagon concentrations were determined following arginine infusion or an oral glucose load in eight patients with diabetes and idiopathic haemochromatosis. The enhanced glucagon response to arginine and the nonsuppressibility of glucagon secretion by oral glucose found in these patients were similar to the results found in the same tests performed in our previous series of patients with “idiopathic” diabetes and at variance with those reported by others in patients with chronic pancreatitis.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 12 (1976), S. 359-365 
    ISSN: 1432-0428
    Keywords: Glomerular filtration rate ; glucagon ; insulin ; kidney ; metabolism ; renal plasma flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of raising arterial plasma glucagon concentrations on kidney glucagon uptake was investigated using an isolated dog kidney perfused with whole blood. In addition, the effect of insulin on the magnitude of glucagon uptake by the kidney was studied at various glucagon concentrations. Renal vein plasma glucagon (V) has been found to be proportional to renal artery plasma glucagon (A). V and A were highly significantly correlated. In the absence of exogenous insulin infusion, V equalled 0.733±0.034 A, while in the presence of insulin V equalled 0.747±0.015 A. When kidney glucagon uptake was measured directly it increased as a function of arterial plasma glucagon. The calculated regression lines were similar in the presence and in the absence of insulin. The mean clearance rate of glucagon by the kidney was similar at low, medium or high concentrations of glucagon and was not affected by the presence of insulin at a mean concentration of 335.7±15.7 μU/ml. At this concentration of insulin, kidney insulin uptake was not affected by glucagon at concentrations ranging from 32 to 1600 pg/ml. Comparison of kidney glucagon uptake at similar arterial plasma glucagon concentrations, but with different renal plasma flows, indicated that kidney glucagon uptake is more dependant on arterial plasma glucagon concentration than on the quantity of glucagon entering the kidney per minute. It is concluded that: 1) kidney glucagon uptake increases as a function of arterial plasma glucagon concentration; 2) the clearance rate of glucagon is similar at low, medium or high arterial concentrations of glucagon; 3) at concentration of 300–350 μU/ml, insulin does not affect kidney glucagon uptake, and 4) at concentrations of glucagon up to 1600 pg/ml, renal insulin uptake is not affected by glucagon. These studies indicate that insulin and glucagon are handled independantly by the kidney of the dog.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Somatostatin ; nicotinic acid ; insulin-dependent diabetes ; glucose ; free fatty acids ; glucagon ; growth hormone ; cortisol ; heparin ; triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The study investigated the respective influences of nicotinic acid and somatostatin on plasma concentrations of blood glucose, free fatty acids, glucagon, growth hormone and cortisol in insulin-dependent diabetic subjects. After administration of nicotinic acid alone, marked depression of plasma FFA was accompanied by significant increases of plasma glucagon, growth hormone and cortisol. The glucagon and growth hormone responses to nicotinic acid were significantly reduced when plasma FFA were raised by intravenous administration of heparin and triglycerides. Somatostatin alone induced a significant decrease in blood glucose, plasma glucagon and growth hormone concentrations. Plasma FFA remained unchanged. Somatostatin did not modify the nicotinic acid-induced fall in plasma FFA, but completely blocked the corresponding increments in glucagon and growth hormone. The cortisol rise was not altered by somatostatin. Rebound of glucagon and growth hormone levels were seen upon discontinuation of the somatostatin administration. These results demonstrate that the plasma FFA concentration plays a role in the regulation of glucagon and growth hormone secretion in insulin-dependent diabetics. Furthermore, they indicate that somatostatin, previously shown to be capable of negating the stimulatory effect of various factors on glucagon and growth hormone secretion, also affects the response of these hormones to FFA depression.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 15 (1978), S. 411-416 
    ISSN: 1432-0428
    Keywords: Isolated islets ; guinea-pig ; prostaglandin synthesis ; glucagon secretion ; arginine ; noradrenaline ; indomethacin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have demonstrated that prostaglandins stimulate glucagon secretionin vitro andin vivo. The present work was aimed at investigating the influence of two inhibitors of prostaglandin synthesis, isopropyl-2 nicotinoyl-3 indole (L8027) and indomethacin, on basal and arginine- or noradrenaline-stimulated glucagon release from isolated guinea-pig islets incubated in the absence of glucose. L8027 (10−4 and 10−5 mol/l) did not alter basal glucagon release, blocked almost completely the glucagon response to arginine (10−2 mol/l), had no effect on the glucagon release induced by noradrenaline (10−4H mol/l), but reduced the stimulatory effect of a lower concentration of noradrenaline (5.10−7 mol/l). The kinetic study of this inhibitory effect demonstrated that (1) it necessitates preincubation of the islets with L8027 for 30 minutes before the addition of arginine, (2) after a short preincubation period (30 minutes) in the presence of L8027, removal of the inhibitor at the time of arginine stimulation resulted in enhanced glucagon response, (3) on the contrary, after a prolonged incubation period (75 min) with arginine and L8027, the inhibitory effect remained transiently detectable after removal of L8027. Indomethacin similarly blocked arginine- and noradrenaline-induced glucagon secretion. These results suggest that an intra-insular synthesis of prostaglandins is involved in the A cell response to arginine and noradrenaline.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Continuous subcutaneous infusion ; Type 1 diabetes ; glucagon ; insulin ; management ; non-esterified fatty acids ; pump
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Interruption of a continuous subcutaneous insulin infusion, most often due to technical problems occurring during the night, is a not uncommon event whose metabolic consequences have received relatively little attention until now. We have therefore investigated the changes in blood glucose, plasma non-esterified fatty acids, 3-hydroxybutyrate, glucagon and free insulin in eight C-peptide negative Type 1 diabetic patients whose pumps were deliberately stopped between 23.00 h and 05.00 h. A control test with the pump functioning normally was carried out in each patient and the studies were randomized. Considering the values at 23.00 h as reference, interruption of the insulin infusion resulted in (1) a rapid decrease in plasma free insulin significant after 1 h and reaching a nadir of 6±2 mU/l after 6 h; (2) a rise in blood glucose which was significant at hour 3 and reached 17.4±1.9 mmol/l at hour 6; (3) a moderate increase in plasma non-esterified fatty acids which remained in the range of 700–800 μmol/l; (4) an early and linear rise in plasma 3-hydroxybutyrate, significant after 1 h and averaging 1290±140 μmol/l after 6 h; (5) a late increase (hour 5) in plasma glucagon. The second aim of our study was to provide for the patient a precise scheme of insulin supplements administered via the pump and based on blood glucose monitoring (Dextrostix — Glucometer) and semi-quantitative evaluation of ketonuria (Acetest). Resetting the pump at its basal rate at 05.00h and giving insulin supplements (2–8 U) at 06.45 h (with the usual breakfast dose) and again at 10.00 h have proved efficacious in restoring satisfactory metabolic control by noon the day after starting the experiment. These results form practical recommendations to patients undergoing this type of accident.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Continuous subcutaneous infusion ; Type 1 diabetes ; glucagon ; growth hormone ; insulin ; non-esterified fatty acids ; pump ; somatostatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the respective roles of insulin deprivation and counter-regulatory hormones in the metabolic deterioration after a nocturnal interruption of continuous subcutaneous insulin infusion in Type 1 (insulin-dependent) diabetic patients without residual insulin secretion. Changes in blood glucose, plasma non-esterified fatty acids, 3-hydroxybutyrate, glucagon, growth hormone, cortisol and free insulin in seven patients whose pumps were deliberately stopped between 23.00 h and 05.00 h were compared in two randomized tests carried out either during an intravenous somatostatin infusion at a constant rate of 250 μg/h from 22.00 h until 07.00 h (somatostatin test) or during a saline infusion (control test). Arrest of the pumps resulted in a rapid (already significant after 1 h) and progressive (nadir after 5–6 h) decrease in plasma free insulin concentrations with no statistically significant differences between the two tests. Somatostatin remarkably depressed basal levels of growth hormone and the late significant increase in glucagon (+39±14 pg/ml at 05.00 h, 2p〈 0.05) observed during the control test. In contrast, cortisol secretion was not inhibited. The sharp linear increase in blood glucose observed from 01.00 to 05.00 h (38±4 μmol·l-1· min-1) in the control test was fully suppressed with a paradoxical tendency to hypoglycaemia until 03.00 h and a less steep rise from 03.00 to 05.00 h (18±5 μmol·l-1·min-1, 2p〈0.05) during the somatostatin test. Initial plasma non-esterified fatty acids levels were slightly higher on somatostatin but did not show any statistically significant rise despite arrest of the pump, contrasting with the increase from 491±27 to 741±96 μmol/l (2p〈0.05) in the control test. Consequently, plasma non-esterified fatty acids levels from 01.00 to 05.00 h were not significantly different between the two tests. The abrupt rise in 3-hydroxybutyrate from 00.00 to 05.00 h (3.0±0.5 μmol·l-1·min-1) in the control test was not altered by somatostatin until 03.00 h. In contrast, during the last 2 h after arrest of the pump, somatostatin inhibited any further rise in 3-hydroxybutyrate levels. In conclusion, somatostatin significantly reduces metabolic deterioration during a 6-h nocturnal interruption of a continuous subcutaneous insulin infusion. Somatostatin-induced glucagon suppression seems to be involved in reducing hyperglycaemia as well as, together with the somatostatin-induced growth hormone suppression, in the limitation of hepatic ketogenesis in hours 5 and 6 after cessation of insulin supply. In contrast, the early rise in 3-hydroxybutyrateplasma levels is unaffected by somatostatin and thus appears entirely due to the fall in free insulin circulating concentrations.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Glucose clamp ; insulin ; magnesium ; oral glucose tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrophotometry in 10 healthy volunteers during an oral glucose tolerance test and during an euglycaemic hyperinsulinaemic glucose clamp. At min 180 and 210 of the oral glucose tolerance test, a significant decline in plasma magnesium levels (p 〈 0.01 andp 〈 0.05 respectively) and a significant increase in erythrocyte magnesium levels (p 〈 0.01 andp 〈 0.05 respectively) were observed. Similar changes were seen during the second hour of the glucose clamp, during which euglycaemia (4.1 ± 0.4 mmol/1) was maintained despite hyperinsulinaemia (110–130 mU/1). During in vitro incubations, glucose (5 mmol/1) did not modify erythrocyte magnesium levels. In contrast, erythrocyte magnesium levels were significantly increased (p 〈 0.01) by insulin (100 mU/1), an effect entirely abolished by ouabain (5 .10−4 mol/1). These results suggest that insulin induces a shift of magnesium from the plasma to the erythrocytes both in vivo and in vitro. These data may help to interprete the abnormalities in magnesium circulating levels frequently reported in diabetic patients.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Erythrocyte ; Type 2 (non-insulin-dependent) diabetes ; insulin ; insulin-resistance ; magnesium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrometry in 12 healthy subjects and 12 moderately obese patients with Type 2 (non-insulin-dependent) diabetes mellitus. Basal plasma and erythrocyte magnesium levels were significantly lower in diabetic patients than in control subjects. In vitro incubation in the presence of 100 mU/l insulin significantly increased magnesium erythrocyte levels in both control subjects (p〈0.001) and patients with diabetes (p〈0.001). However, even in the presence of 100mU/l insulin, the erythrocyte magnesium content of patients with Type 2 diabetes was lower than that of control subjects. The in vitro dose-response curve of the effect of insulin on magnesium erythrocyte accumulation was shifted to the right when red cells of diabetic patients were used, with a highly significant reduction of the maximal effect. Such reduction of the maximal effect of insulin suggests that the impairment of insulin-induced erythrocyte magnesium accumulation observed in Type 2 diabetic patients results essentially from a post-receptor defect. In the diabetic patients, the Δ increase in erythrocyte magnesium levels (calculated as the net increase between basal and 100 mU/l insulin-induced erythrocyte magnesium levels) was negatively correlated with plasma insulin levels (r=−0.86; p〈0.001) and with body mass index (r=−0.90; p〈0.001); it was positively correlated with the glucose disappearance constant Kg after intravenous glucose injection (r=0.79; p〈0.01), with the amount of glucose required to keep euglycaemia despite hyperinsulinaemia in a glucose clamp (r=0.88; p〈0.001), and with the metabolic clearance rate of glucose during the clamp (r=0.82; p〈0.001). These results demonstrate that insulin-induced erythrocyte magnesium accumulation is impaired in patients with Type 2 diabetes and that such defect is correlated to impaired insulin-mediated glucose disposal in these patients.
    Type of Medium: Electronic Resource
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