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  • 1
    ISSN: 1432-0428
    Keywords: Glibenclamide ; DIRA ; gastrointestinal hormones ; duodenal mucosa extracts ; insulin secretion ; pancreas ; B-cells ; gastrointestinal factors ; insulinotrophic action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments were performed in order to study a possible participation of gastrointestinal factors in the insulinotrophic action of glibenclamide in man. Six healthy volunteers received 5 mg glibenclamide in 50 ml saline orally. Biopsies were taken from the duodenal mucosa before and after administration of the drug. The duodenal insulinreleasing activity (DIRA) was assayed in the extracts of the biopsy material by using an in situ pancreas preparation of rat. The corresponding drug, IRI and glucose levels were measured in peripheral blood. The values of IRI correlated with both the prior elevation of DIRA and the increasing levels of the drug in the blood. These data indicate that glibenclamide might stimulate the release of gut factor(s) which, in turn, could possibly sensitize the pancreas response to the drug.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Somatostatin ; indirect calorimetry ; glucose oxidation ; insulin deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the basal state the body utilizes glucose at a rate of 2.2–2.3 mg· kg-1·min-1; of this approximately 1.2–1.3 mg · kg-1 · min-1 is oxidized, while the remaining 1.0 mg · kg-1·min-1 must be utilized by non-oxidative pathways. Little information is, however, available concerning the insulin dependency of these processes. To examine the role of basal insulin levels on glucose oxidation, glucose storage and total body glucose uptake, somatostatin (10 μg/min) was infused for 2 h in nine volunteers while maintaining plasma glucose concentration constant at basal levels by an exogenous glucose infusion. Basal plasma insulin fell by about 50% (13±2 to 7±1mU/l, p〈0.01). Total body glucose metabolism (3H-3-glucose) declined from 2.3±0.1 to 1.9±0.1mg· kg-1·min-1 (p〈0.01). This decrease was entirely accounted for by a fall in basal glucose oxidation (measured by indirect calorimetry) from 1.3±0.1 to 0.7±0.1 mg·kg-1·min-1 (p〈 0.001). To assess the specific role of insulin deficiency in the decline in glucose oxidation, subjects were restudied with somatostatin plus basal insulin replacement (0.07 mg ·kg-1· min-1). Fasting insulin concentration (14±1 mU/1) remained constant during somatostatin plus insulin infusion (13±1mU/l) and basal rates of glucose oxidation (1.2±0.1 mg · kg-1·min-1) and total body glucose uptake did not change significantly. After 2 h, the basal insulin infusion was stopped and somatostatin was continued. Over the subsequent hour, glucose oxidation declined by 0.4±0.1 mg· kg-1 · min-1. This decrease was associated with a parallel decrease in total body glucose uptake of 0.4±0.1 mg·kg-1 ·min-1. These results indicate that approximately 50% of basal glucose oxidation is dependent upon basal insulin secretion. Non-oxidative pathways of glucose metabolism under basal conditions appear to be insulin independent.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Insulin resistance ; lipid oxidation ; glycogen synthase ; glycogen phosphorylase ; glycogen cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A metabolic hypothesis is presented for insulin resistance in obesity, in the presence or absence of Type 2 (non-insulin-dependent) diabetes mellitus. It is based on physiological mechanisms including a series of negative feed-back mechanisms, with the inhibition of the function of the glycogen cycle in skeletal muscle as a consequence of decreased glucose utilization resulting from increased lipid oxidation in the obese. It considers the inhibition of glycogen synthase activity together with inhibition of glucose storage and impaired glucose tolerance. The prolonged duration of increased lipid oxidation, considered as the initial cause, may lead to Type 2 diabetes. This hypothesis is compatible with others based on the inhibition of insulin receptor kinase and of glucose transporter activities.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Oral tolbutamide test ; intravenous tolbutamide test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La durée de l'oTT a été prolongée à 140 min pour permettre l'observation de la remontée (rebound) qui suit la chute de la glycémie et la comparaison avec PivTT. Les effets indésirés de l'hypoglycémie, observés après l'ingestion de 2 g de tolbutamide, ont été évités en réduisant la dose à 1 g chez 18 patients et à 1.5 g chez 31 autres. Le tolbutamide a été administré en même temps qu'une dose double de bicarbonate de sodium. La concordance entre l'ivTT et l'oTT était bonne dans 35%, moyenne dans 38% et mauvaise dans 27% des cas, On suggère que ces résultats insatisfaisants sont dus à des vitesses différentes d'absorption du tolbutamide. L'utilisation de l'oTT prolongé n'est pas recommandé en tant que procédé pour diagnostiquer le diabète.
    Abstract: Zusammenfassung Der oTT wird auf 140 min verlängert, um gleich wie beim ivTT den Wiederanstieg des Blutzuckers beurteilen zu können. Um die mit 2g Tolbutamid beobachteten Hypoglykämien auszuschließen, wurde die Dosis bei 18 Patienten auf 1 g und bei 31 Patienten auf 1.5 g gesenkt und zusammen mit der doppelten Dosis Natrium-Bicarbonat oral verarbeitet. Gute Übereinstimmung zwischen oTT und ivTT wurde in 35%, mäßige in 38% und schlechte Übereinstimmung in 27% der Fälle gefunden. Es wird vermutet, daß die ungenügende Übereinstimmung der beiden Teste auf unterschiedlichen Absorptionsraten von Tolbutamid beruht. Der verlängerte oTT wird für die Zusatzdiagnostik des Diabetes mellitus nicht empfohlen.
    Notes: Summary The duration of the oral tolbutamide Test (oTT) was extended to 140 min to allow the observation of the rebound following the blood sugar fall and the comparison with the ivTT. The undesired effects of the hypoglycaemia observed after the ingestion of 2g tolbutamide were prevented by reducing the dose of the drug to 1 g in 18 patients and to 1.5 g in 31 others. Tolbutamide was given together with the double amount of sodium bicarbonate. The agreement of ivTT and oTT was good in 35%, fair in 38% and poor in 27% of the cases. It is suggested that these unsatisfactory results are due to different tolbutamide absorption rates. The use of the prolonged oTT is not recommended as a tool for the diagnosis of diabetes.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords Substrate oxidation ; glycogenolysis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Resting, post-absorptive endogenous glucose production (EGP), fractional gluconeogenesis and liver glycogen concentration were assessed in 6 lean and 5 obese non-diabetic subjects undergoing elective abdominal surgery. During the 2 days preceding these measurements, 0.3 g/day U-13C glucose had been added to their usual diet to label their endogenous glycogen stores. On the morning of day 3, EGP was measured with 6,6-2H glucose. Their endogenous 13C glycogen enrichment was calculated from 13CO2 and respiratory gas exchanges. Fractional gluconeogenesis was assessed as 1-(13C glucose/13C glycogen) · 100. EGP was similar in lean subjects (113 ± 5 mg/min) and in obese subjects (111 ± 6). Fractional gluconeogenesis was higher in obese (59 ± 10 %) than in lean subjects (29 ± 8 %). However, overall EGP remained constant due to a decrease in glycogenolysis. Since an increased gluconeogenesis and a decreased glycogenolysis may both contribute to increase liver glycogen concentration in obesity, hepatic glycogen concentrations were assessed in hepatic needle biopsies obtained during surgery. Hepatic glycogen concentrations were increased in obese patients (515 ± 38 mg/g protein) compared to lean subjects (308 ± 58, p 〈 0.05). It is concluded that in obese patients: a) fractional gluconeogenesis is increased; b) overall EGP is unchanged due to a proportional inhibition of glycogenolysis; c) liver glycogen concentration is increased. [Diabetologia (1997) 40: 463–468]
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 5 (1969), S. 284-292 
    ISSN: 1432-0428
    Keywords: Glucose ; insulin ; palmitate ; fatty acids ; CO2 ; glycogen ; lipogenesis ; esterification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le tissu adipeux épididymaire du rat a été incubé avec du glucose différemment marqué au 14O et l'effet du palmitate lié à l'albumine a été étudié en l'absence et en présence d'insuline. Aucune inhibition, par le palmitate, du métabolisme du glucose n'a été observée; au contraire, il a été démontré que le palmitate stimule les différentes voies du métabolisme du glucose, en particulier la néosynthèse des acides gras. Les résultats sont discutés en fonction du métabolisme du glucose et du palmitate dans la cellule adipeuse, et en fonction du rôle tenu in vivo par le tissu adipeux dans la diminution de l'assimilation du glucose observée dans des conditions qui élèvent anormalement le taux des acides gras libres sériques.
    Abstract: Zusammenfassung Das epididymale Fettgewebe der Ratte wurde mit verschieden markierter 14C-Glucose inkubiert, und der Effekt von mit Eiweiß gebundenem Palmitat in Ab- und Anwesenheit von Insulin untersucht. Es wurde keine Hemmung des Glucosemetabolismus durch Palmitat beobachtet; hingegen wurde erwiesen, daß Palmitat die verschiedenen Wege des Glucosemetabolismus anregt, besonders die Neosynthese der Fettsäuren. Die Resultate werden wie folgt diskutiert: 1. im Hinblick auf den Metabolismus von Glucose und Palmitat in der Fettzelle, 2. im Hinblick auf die in vivo-Rolle des Fettgewebes bei der Verminderung der Glucoseassimilierung. Diese Verringerung wurde unter Bedingungen beobachtet, die den Serumspiegel der freien Fettsäuren ungewöhnlich stark erhöhen.
    Notes: Summary The rat epididymal fat tissue was incubated with glucose differently labelled with 14C, and the effect of palmitate bound to albumin was studied in the absence or presence of insulin. No inhibition by palmitate of the glucose metabolism was observed. On the contrary, it was demonstrated that palmitate stimulates the different pathways of the glucose metabolism, particularly the fatty acid neosynthesis. The results are discussed in relation to the glucose and palmitate metabolism in the adipose cell, and in relation to the role in vivo of the adipose tissue in the decrease of the glucose assimilation observed in conditions which abnormally increase the serum level of free fatty acids.
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  • 7
    ISSN: 1432-0428
    Keywords: Intravenous tolbutamide test ; oral tolbutamide test ; glucose ; serum-insulin ; serum tolbutamide ; tolbutamide action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez 12 sujets normaux l'oTT et l'ivTT ont été étudiés en déterminant simultanément la glycémie, l'insuline sérique (IRI) et le tolbutamide du sérum. D'après les résultats il est possible de déduire deux mécanismes d'action différents du tolbutamide administré oralement. Ils dépendent de la vitesse d'absorption de la drogue. Quand le tolbutamide est absorbé rapidement, il se produit une sécretion d'insuline quiest responsable de la chute de la glycémie. Quand l'absorption du tolbutamide est lente, la sécrétion d'insuline est faible, mais le taux de la glycémie diminue quand même. Les trois hypothèses suivantes sont proposées: soit l'insuline qui apparaît dans la veine pancréatique ne peut pas être mesurée á la périphérie et agit surtout dans le foie, soit la faible concentration de tolbutamide dans le sérum ne provoque qu'une légère sécrétion d'insuline, mais une inhibition importante de la sécrétion de glucagon, qui est responsable de l'hypoglycémie observée. L'action extra-pancréatique des sulfonylurées, en particulier sur le tissu musculaire, peut également jouer un rôle important dans l'explication de ces résultats.
    Abstract: Zusammenfassung Bei 12 normalen Probanden wurde mittels der Bestimmung von Glucose, Serum-Insulin und Serum-Tolbutamid der orale und der intravenöse Tolbutamidtest vergleichend untersucht. Aus den Resultaten ergeben sich zwei verschiedene Wirkungsmechanismen, die von der Tolbutamid-Resorptionsrate abhängig sind. Wird Tolbutamid rasch resorbiert, so erfolgt eine Insulinsekretion, die für den Blutzuckerabfall verantwortlich ist. Geht die Tolbutamidresorption langsam vor sich, so ist die Insulinsekretion gering, aber der Blutzucker fällt trotzdem ab. Zur Erklärung werden drei Hypothesen diskutiert: Entweder ist das Insulin, das in die Pankreasvene sezerniert wird, peripher nicht meßbar und entfaltet seine Wirkung allein an der Leber, oder die niedere Serum-Tolbutamidkonzentration verursacht nur eine unwesentliche Insulinsekretion, dafür eine Hemmung der Glucagonsekretion, die ihrerseits für die Hypoglykämie verantwortlich ist. Auch extrapancreatische Wirkungen der Sulfonylharnstoffe, besonders die auf das Muskelgewebe, werden diskutiert.
    Notes: Summary In 12 normal subjects the oTT and ivTT were studied by simultaneous determination of blood glucose, serum insulin (IRI) and serum tolbutamide. From the results it is possible, to deduce two different mechanisms for the action of the orally administred tolbutamide. They are dependent of the absorption rate of the drug. When tolbutamide is absorbed quickly, insulin secretion follows. It is responsible for the fall of blood sugar. When the tolbutamide absorption is slow, insulin secretion is small, but the blood sugar level is still falling. The three following hypotheses are proposed: either the insulin which appears in the pancreatic vein cannot be measured at the periphery and acts mostly in the liver, or the low concentration of tolbutamide in the serum causes only a slight secretion of insulin, but an important inhibition of the secretion of glucagon which is responsible for the observed hypoglycaemia. Extrapancreatic action of sulphonylurea compounds, particularly on muscle tissue, may too play an important role to explain the results.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 339-343 
    ISSN: 1432-0428
    Keywords: Insulin release ; glibenclamide ; sulfonylureas ; gastrointestinal hormones ; modulation of insulin release ; rat ; intragastric administration ; i. v. injection ; extrapancreatic effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this study was to investigate the influence of glibenclamide on insulin release via insulinotropic gut factors and via a direct action on the pancreas. Maximum peripheral IRI levels appeared 1 minute after intragastric administration of the minimal effective dose of glibenclamide to rats. The corresponding drug levels were high (600 ng/g) in the duodenal mucosa, but low (2 ng/ml) in the peripheral serum. These concentrations were too low to cause insulin release by direct action on the pancreas. Intragastric glibenclamide increased the amount of “duodenal insulin releasing activity” (DIRA) in the mucosa immediately after drug administration. When glibenclamide was dissolved in plasma at a high concentration (1 μg/ml) and then injected into the coeliac trunk of an in-situ rat pancreas preparation, no additional effect on portal IRI levels was measured as compared with injection of serum alone. In contrast significant IRI release was noticed when glibenclamide was dissolved in serum (1 μg/ml) of rats pretreated with the drug intragastrically. The plasma of pretreated rats without addition of glibenclamide was ineffective. The results suggest that glibenclamide may have two effects, one releasing insulin at the pancreas directly, and the other inducing the release of a gastrointestinal factor which amplifies the first effect. Neither glibenclamide nor the factor alone can provoke an IRI release under physiological conditions. The possible importance of these findings for the regulation of insulin secretion is discussed.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Diabetes ; obesity ; glucose storage ; glucose oxidation ; indirect calorimetry ; oral glucose ; tolerance test ; glucose intolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucose disposal of a 100 g glucose load has been determined in 26 obese compared with 10 non-obese subjects by means of a new application of continuous indirect calorimetry. The obese subjects were divided into 4 groups, according to their degree of glucose intolerance and their insulin response to the glucose load. Through this division it appeared that subjects with no glucose intolerance were moderately obese while the groups with glucose intolerance showed a higher degree of obesity, glucose intolerance increasing with age. The 10 obese subjects with no glucose intolerance (group A) presented values for glucose disposal similar to those of the control subjects. The 4 obese subjects with impaired glucose tolerance (group B) showed no significant changes in glucose storage and in basal oxidation, but a significant decrease in oxidation in response to the load (11±2g vs 19±1 g in the control group, p 〈0.02). The 6 obese subjects with overt diabetes and elevated insulin response to the glucose load (group C) showed a significant decrease in glucose storage (34±6 g vs 63±1 g, p 〈 0.001) but not in oxidation. The 6 obese subjects with overt diabetes and decreased insulin response (group D) showed a significant decrease in glucose storage (25±4 g vs 63 ±1 g, p 〈 0.001) and oxidation (12±1 g, vs 19+1 g, p 〈 0.005). These observations show that in obese diabetics, glucose intolerance results primarily from decreased glucose storage and to a lesser extent from a decrease in glucose oxidation.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Diabetes ; obesity ; glucose storage ; glucose oxidation ; indirect calorimetry ; oral glucose tolerance test ; glucose intolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucose disposal of a 100 g glucose load has been determined in 26 obese compared with 10 non-obese subjects by means of a new application of continuous indirect calorimetry. The obese subjects were divided into 4 groups, according to their degree of glucose intolerance and their insulin response to the glucose load. Through this division it appeared that subjects with no glucose intolerance were moderately obese while the groups with glucose intolerance showed a higher degree of obesity, glucose intolerance increasing with age. The 10 obese subjects with no glucose intolerance (group A) presented values for glucose disposal similar to those of the control subjects. The 4 obese subjects with impaired glucose tolerance (group B) showed no significant changes in glucose storage and in basal oxidation, but a significant decrease in oxidation in response to the load (11±2 g vs 19±1 g in the control group, p〈0.02). The 6 obese subjects with overt diabetes and elevated insulin response to the glucose load (group C) showed a significant decrease in glucose storage (34±6 g vs 63±1 g, p〈0.001) but not in oxidation. The 6 obese subjects with overt diabetes and decreased insulin response (group D) showed a significant decrease in glucose storage (25±4 g vs 63 ±1 g, p〈0.001) and oxidation (12±1 g, vs 19±1 g, p〈0.005). These observations show that in obese diabetics, glucose intolerance results primarily from decreased glucose storage and to a lesser extent from a decrease in glucose oxidation.
    Type of Medium: Electronic Resource
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