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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 28 (1985), S. 435-440 
    ISSN: 1432-0428
    Keywords: Glucagon antibodies ; euglycaemia ; glucose ; insulin ; somatostatin ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A potent high-titre glucagon antibody pool was used to induce a state of acute glucagon deficiency in order to investigate the importance of glucagon in maintaining euglycaemia in the fed and fasted anaesthetised rat. Binding characteristics of the antiserum and evidence of its neutralisation of the biological effects of exogenous glucagon are described. The amount of antibody administered was capable of neutralising up to 12 times the total content of glucagon (approximately 1nmol) in the rat pancreas. The hyperglycaemic response to 1.43 nmol exogenous glucagon was significantly inhibited in the rat by glucagon antibodies given intravenously or intraperitoneally (p 〈 0.001). However, no changes in plasma glucose occurred in rats fasted 16 h (4.35±0.1 mmol/l or 24 h (4.0±0.05 mmol/l) after antibody administration. The same dose of glucagon antibodies produced no change in plasma glucose (6.1±0.2 mmol/l), immunoreactive insulin (1.85±0.05 μg/l) or immunoreactive somatostatin (110±30 ng/l) in rats after antibody administration. Antibody excess, equivalent to a binding capacity for glucagon of 40 nmol/l in the plasma of recipient animals, was demonstrable at all times after passive immunisation. The absence of any affect on glucose concentrations following immunoneutralisation of glucagon suggests that glucagon secretion may not be a major factor in the maintenance of euglycaemia in the rat.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 28 (1985), S. 441-444 
    ISSN: 1432-0428
    Keywords: Paracrine ; insulin secretion ; glucagon secretion ; glucagon antibodies ; arginine ; glucose ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of glucose and arginine on insulin secretion in the presence of glucagon antibodies were investigated in rats in vivo. In contrast to controls, animals given glucagon antibodies showed an inhibition of arginine-stimulated (p 〈 0.001), but not glucose-stimulated, insulin secretion. That these effects were not due to incomplete neutralisation of endogenous glucagon is evidenced by the presence of large antibody excess throughout the duration of the experiments. Both the glucagonotropic effect of arginine (319 ± 60ng/l, p 〈 0.01) and the insulinotropic effect of exogenous glucagon (8.3 ± 0.8 μg/l, p 〈 0.001) were demonstrable under our experimental conditions in the absence of exogenous glucagon antibodies. These observations suggest that different mechanisms are involved in the stimulation of insulin release by arginine and by glucose, and that glucagon may play an important physiological role in the mediation and regulation of insulin secretion by secretogogues, such as arginine.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 14 (1978), S. 405-412 
    ISSN: 1432-0428
    Keywords: Long-acting glucagon ; Zucker fatty and lean rats ; adenylate cyclase ; radioreceptor assay ; Scatchard analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of chronic treatment with a long-acting glucagon preparation on liver glucagon and insulin receptors, adenylate cyclase and plasma lipids has been examined in Zucker fatty rats (fa/fa) and their lean littermates (Fa/−). Liver insulin and glucagon receptors were examined using radioreceptor assay techniques. Neither fatty nor lean rats showed any change in insulin receptors after glucagon treatment. Glucagon receptors of the fatty rats showed a 33% drop in the number of the glucagon receptors after glucagon treatment, whilst there was no such change in the lean group. Plasma membranes of the treated fatty rats and their controls bound only 50% as much insulin per mg of liver membrane protein as those of the treated lean rats and their controls. Glucagon treatment raised plasma NEFA in lean rats and reduced them in fatty ones. Plasma cholesterol levels were reduced in both groups of animals as were plasma triglycerides, though to a lesser degree in fatty than in lean animals. Glucagon treatment increased basal and stimulated adenylate cyclase activity in the lean rats and even more so in the fatty ones. The data lend no support to the concept that hypertriglyceridaemia in fatty Zucker rats is a consequence of abnormal glucagon responsiveness.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 16 (1979), S. 68-68 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Xylitol ; GIF ; insulin ; diarrhoea ; rat ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Xylitol given by gavage to unadapted rats produced profound diarrhoea and no rise in plasma gastric inhibitory polypeptide (GIP) concentration. In xylitol adapted rats it did not cause diarrhoea but still had no effect upon GIP release in contrast to glucose, which did. In healthy human subjects xylitol taken by mouth in solution as a single 30 g dose produced only a minimal rise in blood glucose and no rise in plasma GIP or insulin concentration. Glucose in similar doses, on the other hand, caused a large rise in all three.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Guar ; GIP ; glucacon-like immunoreactivity ; enteroinsular axis ; insulin ; glucose ; diabetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five healthy volunteers and 6 diabetics were given a mixed test meal on two occasions — once with and once without 10 g guar flour. Addition of guar caused a 47% decrease in maximum post-prandial GIP levels, a 48% decrease in blood glucose and a 48% decrease in plasma insulin in normal subjects. In diabetics, addition of guar caused a 30% reduction in maximum post-prandial GIP and 58% decrease in blood glucose. Four normal and 6 diabetic subjects were given a predominantly carbohydrate meal, again with and without 10 g guar. Addition of guar caused a 78% decrease in blood glucose and a 59% decrease in plasma insulin in normal subjects. In diabetics addition of guar caused a 71% decrease in maximum post-prandial plasma GIP and a 68% decrease in blood glucose. Lowering of post-prandial blood glucose, plasma insulin and GIP levels by guar was statistically significant in every case. Addition of guar to the predominantly carbohydrate meal caused a decrease in total plasma GLI in both normal and diabetic subjects but reached statistical significance only in the normal subjects. There was a highly significant correlation (r=0.83; p〈0.0005) between peak post-prandial insulin levels in normal subjects and the corresponding plasma GIP concentration. The reduction in GIP or GLI secretion may, therefore, be partly responsible for the smaller rise in plasma insulin observed in normal volunteers when guar is added to meals.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 19 (1980), S. 397-401 
    ISSN: 1432-0428
    Keywords: Gastric inhibitory polypeptide (GIP) ; control of GIP ; intestinal perfusion with fat at GIP ; rat C-peptide ; rat intestine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intravenous infusion in anaesthetized rats of rat II C-peptide at a dose which produced circulating levels of 22.8±1.8 nmol/l after 30 min, resulted in a significant reduction (141±7 to 50±4 pmol/1, p〈0.001, mean ± SEM) in the immunoreactive gastric inhibitory polypeptide response to an intestinal perfusion with a fat emulsion. Immunoreactive insulin levels were unchanged from basal in this study. It is suggested that C-peptide must be considered as a candidate for the endocrine pancreatic factor which exerts a negative feedback upon gastric inhibitory polypeptide release.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Diabetes ; pituitary function ; testicular function ; testosterone ; oral anti-diabetic agents ; growth hormone ; impotence ; gonadotrophins ; prolactin ; insulin ; thyrotrophin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pituitary responsiveness to thyrotrophin releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH) was studied in thirty one male diabetics, of whom sixteen were insulin-dependent and fifteen on oral antidiabetic agents. Ten age-matched controls were also studied. TRH and LHRH were simultaneously administered intravenously, each in a small dose of 10 μg followed two hours later by 190 μg and 90 μg respectively. Basal hormone levels were measured in a further group of thirty six patients (twelve on insulin, twelve on oral agents and twelve on dietary restrictions alone). Higher thyrotrophin (TSH) response was observed following the small dose of TRH in the patients treated with oral agents than in the control subjects. The response of prolactin was lower in patients treated with oral agents compared with those treated with insulin. There was no difference in plasma T3 and T4 levels in the patients treated with insulin or oral agents. Significantly higher basal growth hormone (GH) levels were observed in the diabetics. The insulin-dependent group showed a more marked response of GH to TRH/LHRH. No response was observed in the controls. Plasma testosterone levels were significantly lower in the oral agent group (13.8 nmol/l) than in the insulin group (19.4 nmol/l), patients on dietary restrictions (18.4 nmol/l) and the control subjects (19.0 nmol/l). The LH response to the smaller dose of LHRH was impaired in patients on insulin and oral agents. There was a significant difference in FSH response between impotent and sexually normal patients.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Islet secretion ; A and D cells ; vasculature ; perfusion ; mantle ; interactions ; paracrine ; insulin ; glucagon ; somatostatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have suggested that the order of cellular vascular perfusion within the islet is important in the regulation of islet hormone secretion. Anatomically, the A and D cells appear to be randomly dispersed throughout the mantle. Although islet capillary blood flow is known to be from the B-cell core to the A- and D-cell mantle, it has not yet been established whether the cells of the mantle may influence one another vascularly. Rat pancreata were perfused in vitro anterogradely and retrogradely with or without glucagon antibody in order to determine the order of cellular perfusion and interaction between the A and D cells in the islet mantle. Anterograde infusion of glucagon antibody did not affect insulin secretion, but rapidly decreased somatostatin secretion −46±8%, (p〈0.005). Retrograde infusion of glucagon anti body decreased insulin secretion (−27±8%, p〈0.005) but had no effect upon somatostatin secretion. This study not only confirms a core to mantle islet perfusion but also establishes that the A cell precedes the D cell in the terms of vascular perfusion. Thus within the islet, vascular borne insulin regulates the release of glucagon, which in turn, regulates the release of somatostatin. Somatostatin is vascularly neutral owing to its downstream position in the sequence (B to A to D) of cellular perfusion.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 41 (1998), S. 1309-1313 
    ISSN: 1432-0428
    Keywords: Keywords GLP-1 ; GIP ; insulin ; glucose ; elderly ; menopause.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ageing is one of the major risk factors for glucose intolerance including impaired glucose tolerance and Type II (non-insulin-dependent) diabetes mellitus. Reduced insulin secretion has been described as part of normal ageing although there is no information on age-related changes in the secretion of the major insulinotropic hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (7–36 amide) (GLP-1). We assessed the entero-insular axis in 6 young premenopausal and 6 older postmenopausal women following treatment with oral carbohydrate. Insulin and glucose integrated responses were similar in the younger and older groups. Total integrated responses for GIP and GLP-1 were considerably greater in the older subjects. A positive correlation between age and total integrated responses for glucose (r = 0.65; p 〈 0.02) as well as GLP-1 (r = 0.85; p 〈 0.001) was seen. We hypothesise that an age-related impairment of insulin secretion to insulinotropic hormones, GIP and GLP-1, contributes to a reduction in glucose tolerance in this age group. The pronounced compensatory increase in postprandial secretion of GIP and GLP-1 provides further evidence not only for the negative feedback relation between incretin and insulin secretion but also for the importance of the entero-insular axis in the regulation of insulin secretion. [Diabetologia (1998) 41: 1309–1313]
    Type of Medium: Electronic Resource
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