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  • 1
    ISSN: 1432-0428
    Keywords: hepatic glycogenolysis ; gastric inhibitory polypeptide (GIP) ; insulin ; glucagon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of porcine gastric inhibitory polypeptide on hepatic glycogen metabolism was investigated in the isolated in situ perfused rat liver. Glycogenolysis was stimulated by infusion of glucagon into the portal vein (half maximal effective portal vein concentration ∼30 pmol/1). When glucagon was infused at a final portal vein concentration of 0.5 nmol/l, simultaneous addition of insulin inhibited the glucagon-dependent glycogenolysis in a dose-dependent way (half maximal effective concentration for insulin about 2 nmol/l). Gastric inhibitory polypeptide alone at a concentration of 1 nmol/l reduced glucagon-dependent glycogenolysis only slightly. However, when infused simultaneously at low insulin concentrations (0.1 nmol/1), gastric inhibitory polypeptide suppressed hepatic glucose production dose-dependently up to 70%. The data suggest that gastric inhibitory polypeptide exerts direct metabolic effects on hepatic glycogen metabolism predominantly in a situation where insulin is simultaneously present, e.g. following ingestion of glucose.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Enteroinsular axis ; incretin effect ; cholecystokinin ; gastric inhibitory polypeptide ; insulin secretion ; phenylalanine ; amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intraduodenal phenylalanine administration (333 mg/min over 60 min) released endogenous cholecystokinin in healthy young subjects as demonstrated radioimmunologically and by intraduodenal bilirubin and pancreatic enzyme output. Concomitantly, there was only a small increase over basal in circulating immunoreactive-insulin and immunoreactive-C-peptide concentrations. In healthy volunteers intraduodenal infusions of saline (10 ml/min), glucose (333 mg/min) or phenylalanine (333 mg/min) were performed for 60 min when plasma glucose was clamped at approximately 8 mmol/l. Phenylalanine enhanced immunoreactive-insulin and immunoreactive-C-peptide responses three-fold more than did the same amount of glucose. Immuno-reactive gastric inhibitory polypeptide responses were small and not different after glucose and phenylalanine administration. Immunoreactive cholecystokinin was significantly stimulated to 9.4±1.4pmol/l only by intraduodenal phenylalanine. Plasma phenylalanine concentrations increased into the supraphysiological range (approximately 1.5 mmol/l). Intravenous infusions of phenylalanine achieving plasma concentrations of 1.2 mmol/l stimulated insulin secretion at elevated plasma glucose concentrations (approximately 8 mmol/l clamp experiments), but had no effect at basal plasma glucose concentrations. A small increase in cholecystokinin also was observed. Intravenous infusions of synthetic sulphated cholecystokinin-8 leading to plasma concentrations in the upper postprandial range (8–12 pmol/l) did not augment the immunoreactive-insulin or immunoreactive-C-peptide levels during hyperglycaemic clamp experiments, in the absence or presence of elevated plasma phenylalanine concentrations. It is concluded that the augmentation of the glucose-induced insulin release by intraduodenal administration of phenylalanine cannot be related to cholecystokinin release, but rather is explained by the combined effects of elevated glucose and phenylalanine concentrations. In man, cholecystokinin does not augment insulin secretion caused by moderate hyperglycaemia, elevations of phenylalanine concentrations, or combinations thereof.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: GIP ; gastrin ; insulin ; incretin ; chronic pancreatitis ; test meal ; malassimilation of fat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-nine patients with chronic pancreatitis had a significantly greater IR-GIP response to a test meal than 15 controls. This increased response was not related to the degree of steatorrhoea or glucose intolerance. It was most marked in a group of patients with moderately impaired IRI release and medium steatorrhoea. From this is concluded that the IR-GIP response to a test meal is determined by at least two factors: 1. feedback control via insulin secretion, 2. assimilation of fat. In chronic pancreatitis endocrine insufficiency may induce an exaggerated GIP response and severe exocrine insufficiency may prevent fat induced GIP release. Gastrin is not involved in the different GIP response in patients with chronic pancreatitis.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: GIP release ; chronic pancreatitis ; steatorrhea ; maldigestion ; pancreatin ; incretin effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of impaired digestion on nutrient induced release of gastric inhibitory polypeptide (GIP) and insulin have been investigated in patients with chronic pancreatitis. All patients had massive steatorrhea (〉25 g/24 h), and glucose intolerance. A standard liquid test meal comprising fat and glucose were ingested with or without pancreatic enzyme substitution (9.0 g pancreatin). In the presence of pancreatin the response of serum levels of GIP to the test meal was significantly enhanced (81.2 vs 194.5 μg/l×180 min). Concurrently, the insulin response was augmented (3.4 vs 6.4 U/l×180 min), resulting in improved glucose tolerance. Addition of pancreatin also significantly augmented the GIP response to oral fat (100g), but not to oral glucose (100g). In patients with pancreatogenic steatorrhea the insulin response to an IV glucose infusion (0.7g/ kg/h for 90 min) was augmented by oral fat only after addition of 9.0 g pancreatin to the fat load (3.5 vs 7.3 U/l×180 min). After restoration of the GIP response to fat by pancreatin, the inhibitory effect of IV glucose on fat-induced GIP increase was restored. These data indicate that the GIP response to a mixed meal or triglycerides is dependent on the absorption of nutrients. In patients with chronic pancreatitis improvement of pancreatogenic insufficiency reverses the impaired GIP response, restores the incretin effect of fat, and improves glucose tolerance.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: GIP ; insulin ; incretin ; enteroinsular axis ; rat gut extract ; intestinal hormones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The action of watery rat gut extracts on glucose-induced insulin release in anaesthetized rats was examined before and after removal of GIP by immunoadsorption. Infusions of GIP-containing rat gut extracts nearly doubled the insulin release induced by intravenous glucose (1g · kg−1 · h−1). Peak insulin secretion was 98±11 mU/l (mean±SEM) after intravenous glucose and increased to 178±16 mU/l following infusion of glucose plus gut extract (p〈0.005). After injection of GIP antiserum in sufficient amounts to neutralize the GIP activity in the gut extract preparation, the additional insulin release due to the gut extract was reduced by only 30%. After complete removal of GIP from gut extracts by immunoabsorption, more than 50% of the incretin effect remained. These data suggest that the insulinotropic activity of rat gut extracts can only be partially related to GIP. The existence of additional insulinotropic gut factors which may also be released following oral glucose is postulated.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 29 (1986), S. 46-52 
    ISSN: 1432-0428
    Keywords: Insulin secretion ; Type 2 (non-insulin-dependent) diabetes ; incretin effect ; gastrointestinal hormones ; gastric inhibitory polypeptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Integrated incremental immunoreactive insulin and connecting peptide responses to an oral glucose load of 50 g and an “isoglycaemic” intravenous glucose infusion, respectively, were measured in 14 Type 2 (non-insulin-dependent) diabetic patients and 8 age- and weight-matched metabolically healthy control subjects. Differences between responses to oral and intravenous glucose administration are attributed to factors other than glucose itself (incretin effect). Despite higher glucose increases, immunoreactive insulin and connecting peptide responses after oral glucose were delayed in diabetic patients. Integrated responses were not significantly different between both groups. However, during “isoglycaemic” intravenous infusion, insulin and connecting peptide responses were greater in diabetic patients than in control subjects as a consequence of the higher glycaemic stimulus. The contribution of incretin factors to total insulin responses was 72.8 ± 6.9% (100% = response to oral load) in control subjects and 36.0 ± 8.8% in diabetic patients (p ≦ 0.05). The contribution to connecting peptide responses was 58.4 ± 7.6% in control subjects and 7.6 ± 14.5% (p ≦ 5 0.05) in diabetic patients. Ratios of integrated insulin to connecting peptide responses suggest a reduced (hepatic) insulin extraction in control subjects after oral as compared to intravenous glucose. This was not the case in diabetic patients. Immunoreactive gastric inhibitory polypeptide responses were not different between control subjects and diabetic patients. A reduced or lost incretin effect in the face of normal gastric inhibitory polypeptide response in Type 2 diabetic patients may be explained by decreased sensitivity of the B cells towards the insulinotropic effect of gastric inhibitory polypeptide or to hyposecretion or reduced effectiveness of as yet unidentified humoral or nervous gut factors with incretin activity.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 11 (1975), S. 113-117 
    ISSN: 1432-0428
    Keywords: Bile salt absorption ; biguanides ; phenformin ; buformin ; metformin ; active transport ; bile salt malabsorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of blood sugar lowering biguanides (phenethyl-, butyl- and dimethylbiguanide) upon jejunal and ileal transport of bile salts (tauro- and glycocholate) was tested in rat small intestine by an in vitro technique. Biguanides inhibited active transport of bile salts in the ileum, but did not affect diffusional absorption of bile salts in the jejunum. The inhibitory effect was time-dependent and not reversible under in vitro incubation conditions, suggesting that biguanides must enter intestinal mucosal cells in order to exert their inhibitory action on active transport of glucose analogues, amino acids, calcium and bile salts. Since biguanides achieve high tissue concentrations in the small intestine even after parenteral administration, inhibition of ileal bile salt reabsorption by biguanides could possibly explain the lipid- and cholesterol-lowering effect of these oral antidiabetic drugs.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Hyperinsulinaemia ; insulin resistance ; insulin degradation ; haemochromatosis ; cirrhosis ; insulin ; glucagon ; C-peptide ; gastric inhibitory polypeptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study investigated early alterations of glucose metabolism in idiopathic haemochromatosis. Circulating concentrations of glucose, insulin, C-peptide, glucagon, and gastric inhibitory polypeptide (GIF) were measured after a 100-g oral glucose load in 10 men with idiopathic haemochromatosis in the non-cirrhotic stage of the disease. All had normal glucose tolerance and normal body weight. Ten matched healthy subjects were studied as controls. Insulin concentrations increased to significantly higher levels in patients with idiopathic haemochromatosis than in the control subjects from 30 to 180min after the glucose load (p〈0.01), while fasting insulin concentrations were not significantly different (p〉 0.05). Concentrations of glucose, glucagon, C-peptide, and GIF were not significantly different at any time (p〉 0.05). Thus, patients with idiopathic haemochromatosis show hyperinsulinaemia and hence insulin resistance without impaired glucose tolerance in the non-cirrhotic stage. Since pancreatic insulin secretion (C-peptide), glucagon secretion, and the entero-insulinar axis (GIP) are not impaired in these non-cirrhotic patients with idiopathic haemochromatosis, iron accumulation in the hepatocytes may be responsible for the impaired insulin effect and may cause impaired hepatic insulin extraction.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Maturity-onset diabetes ; diet ; tolbutamide ; buformin ; body weight ; glucose tolerance ; fasting IRI ; lactate ; pyruvate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Après une période de contrôle de 5 semaines, on a étudié, pendant 8 semaines, chez 103 diabétiques d'âge mûr l'effet thérapeutique du tolbutamide et de la buformine, ainsi que de leur association, sur la tolérance au glucose, l'IRI à jeun, le taux de lactate et de pyruvate. Dans les groupes traités avec la buformine, on a observé une chute de poids significative. Lors du traitement par le tolbutamide, il ne se produisait pas de réduction du poids. Dans tous les groupes étudiés, les valeurs du glucose diminuaient. Lors de la monothérapie avec la buformine les valeurs de l'IRI à jeun avaient tendance à baisser à la fin de la période de traitement. Lors de l'introduction d'une thérapeutique par le tolbutamide, les valeurs de l'IRI à jeun avaient temporairement tendance à monter. — Lors du traitement par la buformine, on n'a pas observé d'augmentation significative des concentrations de lactate et des quotients lactate/pyruvate. De même, lors du traitement par le tolbutamide, les taux de lactate n'étaient pas modifiés. Après introduction d'un traitement par le tolbutamide, les concentrations de pyruvate étaient significativement plus basses à la fin de la période de traitement.
    Abstract: Zusammenfassung An 103 Altersdiabetikern wurde nach einer 5 wöchigen Kontrollperiode 8 Wochen lang der therapeutische Effekt von Tolbutamid und Buformin, sowie deren Kombination hinsichtlich Glucosetoleranz, Nüchtern-IRI, Lactat- und Pyruvatspiegel untersucht. In den mit Buformin behandelten Gruppen trat ein signifikanter Gewichtsabfall ein. Unter Tolbutamidbehandlung trat keine Gewichtsreduktion, ein. In allen untersuchten Kollektiven sanken die Glucosewerte ab. Bei einer Monotherapie mit Buformin zeigten die Nüchtern-IRI-Werte am Ende der Behandlungsperiode eine abfallende Tendenz. Bei Einleitung einer Tolbutamid-behandlung hatten die Nüchtern-IRI-Werte vorüber-gehend eine ansteigende Tendenz. — Ein signifikanter Anstieg der Lactatkonzentrationen und der Lactat/Pyruvat-Quotienten wurde unter Buforminbehandlung nicht beobachtet. Auch unter Tolbutamidbehandlung änderten sich die Lactatspiegel nicht. Nach Einleitung einer Tolbutamidbehandlung lagen die Pyruvatkonzentrationen am Ende der Behandlungsperiode signifikant niedriger.
    Notes: Summary The effects of the administration of tolbutamide, buformin or their combination for 8 weeks on glucose tolerance, fasting IRI and lactate and pyruvate levels in 103 maturity-onset diabetics have been compared with corresponding values during a preceding control period of 5 weeks. The group on buformin showed a significant weight loss. There was no weight loss during tolbutamide treatment. Glucose levels decreased in all groups investigated. Fasting IRI levels showed a tendency to decrease at the end of the buformin monotherapy period. There was a transient tendency for fasting IRI levels to increase at the beginning of tolbutamide therapy. — A significant increase of lactate concentrations and of the lactate/pyruvate quotient was not observed during buformin treatment, nor did tolbutamide induce a change in lactate levels. Pyruvate levels were significantly lowered towards the end of the tolbutamide period.
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  • 10
    ISSN: 1432-0428
    Keywords: Keywords GLP-1 [7 ; 36 amide] ; incretin ; insulin ; glucagon ; pharmacokinetics.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intravenous glucagon-like peptide (GLP)-1 [7–36 amide] can normalize plasma glucose in non-insulin-dependent diabetic (NIDDM) patients. Since this is no form for routine therapeutic administration, effects of subcutaneous GLP-1 at a high dose (1.5 nmol/kg body weight) were examined. Three groups of 8, 9 and 7 patients (61 ± 7, 61 ± 9, 50 ± 11 years; BMI 29.5 ± 2.5, 26.1 ± 2.3, 28.0 ± 4.2 kg/m2; HbA1 c 11.3 ± 1.5, 9.9 ± 1.0, 10.6 ± 0.7 %) were examined: after a single subcutaneous injection of 1.5 nmol/kg GLP [7–36 amide]; after repeated subcutaneous injections (0 and 120 min) in fasting patients; after a single, subcutaneous injection 30 min before a liquid test meal (amino acids 8 %, and sucrose 50 g in 400 ml), all compared with a placebo. Glucose (glucose oxidase), insulin, C-peptide, GLP-1 and glucagon (specific immunoassays) were measured. Gastric emptying was assessed with the indicator-dilution method and phenol red. Repeated measures ANOVA was used for statistical analysis. GLP-1 injection led to a short-lived increment in GLP-1 concentrations (peak at 30–60 min, then return to basal levels after 90–120 min). Each GLP-1 injection stimulated insulin (insulin, C-peptide, p 〈 0.0001, respectively) and inhibited glucagon secretion (p 〈 0.0001). In fasting patients the repeated administration of GLP-1 normalized plasma glucose (5.8 ± 0.4 mmol/l after 240 min vs 8.2 ± 0.7 mmol/l after a single dose, p = 0.0065). With the meal, subcutaneous GLP-1 led to a complete cessation of gastric emptying for 30–45 min (p 〈 0.0001 statistically different from placebo) followed by emptying at a normal rate. As a consequence, integrated incremental glucose responses were reduced by 40 % (p = 0.051). In conclusion, subcutaneous GLP-1 [7–36 amide] has similar effects in NIDDM patients as an intravenous infusion. Preparations with retarded release of GLP-1 would appear more suitable for therapeutic purposes because elevation of GLP-1 concentrations for 4 rather than 2 h (repeated doses) normalized fasting plasma glucose better. In the short term, there appears to be no tachyphylaxis, since insulin stimulation and glucagon suppression were similar upon repeated administrations of GLP-1 [7–36 amide]. It may be easier to influence fasting hyperglycaemia by GLP-1 than to reduce meal-related increments in glycaemia. [Diabetologia (1996) 39: 1546–1553]
    Type of Medium: Electronic Resource
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