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  • 1
    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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  • 2
    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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  • 3
    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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  • 4
    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.
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords Glycogenolysis ; carbohydrate oxidation ; glucagon ; gluconeogenesis ; fructose.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased endogenous glucose production (EGP) and gluconeogenesis contribute to the pathogenesis of hyperglycaemia in non-insulin-dependent diabetes mellitus (NIDDM). In healthy subjects, however, EGP remains constant during administration of gluconeogenic precursors. This study was performed in order to determine whether administration of fructose increases EGP in obese NIDDM patients and obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged obese NIDDM patients and seven middle-aged obese non-diabetic subjects were studied during hourly ingestion of 13C fructose (0.3 g · kg fat free mass−1· h−1) for 3 h. Fructose failed to increase EGP (measured with 6,6 2H glucose) in NIDDM (17.7 ± 1.9 μmol · kg fat free mass−1· min−1 basal vs 15.9 ± 0.9 after fructose), in obese non-diabetic subjects (12.1 ± 0.5 basal vs 13.1 ± 0.5 after fructose) and in lean healthy subjects (13.3 ± 0.5 basal vs 13.8 ± 0.6 after fructose) although 13C glucose synthesis contributed 73.2 % of EGP in lean subjects, 62.6 % in obese non-diabetic subjects, and 52.8 % in obese NIDDM patients. Since glucagon may play an important role in the development of hyperglycaemia in NIDDM, healthy subjects were also studied during 13C fructose ingestion + hyperglucagonaemia (232 ± 9 ng/l) and during hyperglucagonaemia alone. EGP increased by 19.8 % with ingestion of fructose + glucagon (p 〈 0.05) but remained unchanged during administration of fructose or glucagon alone. The plasma 13C glucose enrichment was identical after fructose ingestion both with and without glucagon, indicating that the contribution of fructose gluconeogenesis to the glucose 6-phosphate pool was identical in these two conditions. We concluded that during fructose administration: 1) gluconeogenesis is increased, but EGP remains constant in NIDDM, obese non-diabetic, and lean individuals; 2) in lean individuals, both an increased glucagonaemia and an enhanced supply of gluconeogenic precursors are required to increase EGP; this increase in EGP occurs without changes in the relative proportion of glucose 6-phosphate production from fructose and from other sources (i. e. glycogenolysis + gluconeogenesis from non-fructose precursors). [Diabetologia (1996) 39: 580–586]
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 5 (1969), S. 195-197 
    ISSN: 1432-0428
    Keywords: Insulin ; glucagon ; adipose tissue ; lipolysis ; FFA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé A des concentrations proches de celles qui sont rencontrées dans le plasma humain, le glucagon stimule fortement la lipolyse au niveau de la graisse épididymaire du rat, étudiéein vitro. Les effets de telles concentrations de glucagon sont réduits, voire abolis par l'insuline aux concentrations de 25 et 100μU/ml. Rapprochées de l'effet insulinogénique puissant du glucagon, ces observations peuvent fournir une explication quant au caractère retardé de l'élévation du taux sanguin des acides gras libres observée après injection de glucagonin vivo.
    Abstract: Zusammenfassung Glucagon stimuliert in Konzentrationen, wie sie auch im menschlichen Plasma vorkommen, die Lipolyse im Ratten-Nebenhodenfettgewebein vitro stark. Die Effekte derartiger Glucagonkonzentrationen werden durch Insulin (25–100μE/ml) verringert bis aufgehoben. Unter Berücksichtigung der ausgeprägten Wirkung von Glucagon auf die Insulinfreisetzung können diese Beobachtungen eine Erklärung für die Verzögerung des Anstiegs der freien Fettsäuren im Serum liefern, die man nach Glucagoninjektionenin vivo beobachtet.
    Notes: Summary Glucagon in concentrations similar to those found in human plasma markedly stimulates lipolysis in rat adipose tissuein vitro. The effects of these “physiological” concentrations of glucagon are reduced or abolished by insulin at concentrations of 25 and 100μU/ml. Considering the marked insulinogenic effect of glucagon these observations may provide an explanation for the delayed increase of blood FFA observed after glucagon injectionin vivo.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Glycogenolysis ; carbohydrate oxidation ; glucagon ; gluconeogenesis ; fructose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased endogenous glucose production (EGP) and gluconeogenesis contribute to the pathogenesis of hyperglycaemia in non-insulin-dependent diabetes mellitus (NIDDM). In healthy subjects, however, EGP remains constant during administration of gluconeogenic precursors. This study was performed in order to determine whether administration of fructose increases EGP in obese NIDDM patients and obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged obese NIDDM patients and seven middle-aged obese non-diabetic subjects were studied during hourly ingestion of 13C fructose (0.3 g · kg fat free mass−1 · h−1) for 3 h. Fructose failed to increase EGP (measured with 6,6 2H glucose) in NIDDM (17.7±1.9 Μmol · kg fat free mass−1 · min−1 basal vs 15.9±0.9 after fructose), in obese non-diabetic subjects (12.1±0.5 basal vs 13.1±0.5 after fructose) and in lean healthy subjects (13.3±0.5 basal vs 13.8±0.6 after fructose) although 13C glucose synthesis contributed 73.2% of EGP in lean subjects, 62.6% in obese non-diabetic subjects, and 52.8% in obese NIDDM patients. Since glucagon may play an important role in the development of hyperglycaemia in NIDDM, healthy subjects were also studied during 13C fructose ingestion + hyperglucagonaemia (232±9 ng/l) and during hyperglucagonaemia alone. EGP increased by 19.8% with ingestion of fructose + glucagon (p〈0.05) but remained unchanged during administration of fructose or glucagon alone. The plasma 13C glucose enrichment was identical after fructose ingestion both with and without glucagon, indicating that the contribution of fructose gluconeogenesis to the glucose 6-phosphate pool was identical in these two conditions. We concluded that during fructose administration: 1) gluconeogenesis is increased, but EGP remains constant in NIDDM, obese non-diabetic, and lean individuals; 2) in lean individuals, both an increased glucagonaemia and an enhanced supply of gluconeogenic precursors are required to increase EGP; this increase in EGP occurs without changes in the relative proportion of glucose 6-phosphate production from fructose and from other sources (i. e. glycogenolysis + gluconeogenesis from non-fructose precursors).
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: hypoglycemia ; glucagon ; neonate ; intravenous glucose ; hyperinsulinism ; diabetes ; pancreatic α-cell ; diabetic mother ; portal plasma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Les auteurs ont étudié des nouveau-nés humains pendant les premières heures de la vie. La glycémie, les taux d'insuline et de glucagon dans le plasma portal ont été dosés à intervalles réguliers jusqu'à la 24ème heure après la naissance, de même què au cours d'une surcharge glucosée intraveineuse pratiquée à la 24ème heure. — Un matériel présentant les caractéristiques immunologiques du glucagon pancréatique a été mis en évidence dans le plasma portal des nouveau-nés normaux et de mère diabétique. La surcharge glucosée intraveineuse ne réduit pas le taux de glucagon plasmatique chez le nouveau-né normal ni chez l'enfant de mère diabétique. — Dans la phase tardive de la surcharge glucosée intraveineuse, les valeurs de la glucagonémie portale sont plus élevées chez l'enfant normal que chez le nouveau-né de mère diabétique. L'insulinémie portale est plus élevée chez le nouveau-né de mère diabétique à la 24ème heure de la vie et à la phase initiale de la surcharge glucosée. — L'hypothèse est proposée que la différence de comportement du glueagon pourrait résulter de l'hyperinsulinisme relatif de l'enfant de mère diabétique, l'insuline favorisant la pénétration de glucose dans la cellule α et permettant, par ce mécanisme, une suppression plus efficace de la sécrétion de glucagon.
    Abstract: Zusammenfassung Menschliche Neugeborene wurden während der ersten Lebensstunden untersucht. Blut-glucose, portales Plasmainsulin und Glucagon wurden sowohl in regulären Abständen bis zu 24 Std nach der Geburt als auch während einer intravenösen Glucosebelastung in der 24. Std untersucht. — Eine Substanz mit den immunologischen Charakteristika von Pancreasglucagon wurde im portalen Plasma sowohl von normalen Kindern als auch von Kindern diabetischer Mütter gefunden. Die intravenöse Glucosebelastung hat weder bei den normalen Neugeborenen noch bei den Kindern diabetischer Mütter das Plasmaglucagon unterdrückt. Im Vergleich zu den Kindern diabetischer Mütter wurden bei den normalen Neugeborenen in der späten Phase der intravenösen Glucosebelastung höhere Plasmaglucagonwerte beobachtet. Portales Plasmainsulin war bei den Kindern diabetischer Mütter sowohl nach 24 Std als auch während der ersten Phase des intravenösen Glucosetoleranztests erhöht gefunden worden. — Es wird die Hypothese vorgeschlagen, daß das Verhalten der Unterschiede in der Glucagonsekretion möglicherweise eine Folge des relativen Hyperinsulinismus der Kinder diabetischer Mütter sei, welcher der Glucose den Eintritt in die Zelle durch Insulin erleichtert und so eine effektvollere Glucagonverminderung erlaubt.
    Notes: Summary Human neonates have been studied during the first hours of life. Blood glucose, portal plasma insulin and glucagon have been determined both at regular intervals up to 24 h after birth and during an intravenous glucose load performed at the 24th h. A material presenting the immunological characteristics of pancreatic glucagon has been found in the portal plasma of both normal infants and infants from diabetic mothers (IDM). The intravenous glucose load did not suppress plasma glucagon in the normal neonates nor in the IDM. Higher portal plasma glucagon values were observed in the late phase of the intravenous glucose load in normal neonates compared to IDM. Portal plasma insulin has been found higher in IDM both at the 24th h of life and during the early phase of the intravenous glucose tolerance test. The hypothesis is put forward that the behaviour difference in glucagon secretion might be a consequence of the relative nyperinsulinism of IDM with insulin facilitating the entry of glucose into the α cell thus permitting a more effective glucagon suppression.
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  • 9
    ISSN: 1432-0428
    Keywords: Insulin-treated diabetics ; intravenous arginine ; insulin ; glucagon ; C-peptide ; indomethacin ; prostaglandins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fourteen insulin-treated diabetics were submitted to an arginine infusion test performed with either 11.7 or 5.85mg kg-1 min-1 arginine monohydrochloride infused during 40 min with or without previous oral administration of a low (75+50 mg) or a high (75 mg + 3 mg/kg) dose of indomethacin. Blood glucose, plasma non-esterified fatty acids, insulin, C-peptide and glucagon were determined at regular intervals before, during and after the arginine infusion. These parameters were totally unaffected by the two doses of indomethacin both in the basal state and during the arginine infusions at the two loads tested. Eight subjects had a basal C-peptide level above 0.07 pmol/ml and a mean (± SEM) maximal rise of 0.21±0.04 pmol/ml during the arginine infusion, whereas the remaining six patients had virtually zero values throughout the tests. The arginine-induced plasma glucagon rise was similar for the two rates of arginine infusion; the sum of the increments in plasma glucagon averaged 877±120 and 647±92 pg/ml (p〉0.1) for the high and low rates of arginine infusion, respectively. The magnitude of the blood glucose rise appeared independent of the amount of arginine infused. Confirming previous reports, we found that the blood glucose rise after arginine was three to four times higher in subjects without C-peptide than in subjects with C-peptide. The mean glucagon response did not differ significantly between subjects with or without C-peptide. Thus, residual B cell function determines the magnitude of the blood glucose rise but not the glucagon response after intravenous arginine.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 11 (1975), S. 549-554 
    ISSN: 1432-0428
    Keywords: Free fatty acids ; glucagon ; glucose ; glucose-tolerance ; insulin ; insulin-resistance ; pregnancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased plasma pancreatic glucagon concentrations have been reported during various states of decreased glucose tolerance.In vitro studies have demonstrated that human somatomammotropin stimulates glucagon release. The present investigation aimed at evaluating the role of plasma glucagon in the insulin resistance associated with normal pregnancy. Postprandial samples of plasma were obtained from 156 pregnant women between the 5th and the 40th week of pregnancy and were assayed for blood glucose, plasma insulin, glucagon and free fatty acids. Plasma insulin showed a gradual increase during pregnancy, and reached its maximal values during the last trimester. A moderate but significant increase in plasma glucagon was present between the 16th and the 28th week of gestation, whereas during the first and the last trimester of pregnancy its concentration was similar to that in non pregnant women. Intravenous glucose tolerance was performed during the last trimester and in a group of non pregnant control women. The slight decrease in glucose tolerance and the marked hyperinsulinemia associated with late pregnancy were accompanied by a more rapid and more pronounced decrease in plasma glucagon. A rapid and sustained decrease in glucagon was also observed when plasma FFA were raised by the intravenous administration of a triglyceride emulsion and heparin. These data suggest that glucagon is not involved in the insulin resistance associated with normal human pregnancy.
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