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  • 1
    Electronic Resource
    Electronic Resource
    Pancreatic polypeptide, glucagon and insulin secretion from the isolated perfused canine pancreas (1978)
    Springer
    Diabetologia 14 (1978), S. 413-417 
    Details
    ISSN: 1432-0428
    Keywords: Isolated perfused canine pancreas ; VIP ; GIP ; caerulein ; gastrin ; secretin ; glucagon ; bombesin ; acetyl choline ; adrenaline ; release of insulin ; release of glucagon ; release of PP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The release of pancreatic polypeptide (PP) by gut hormones, acetyl choline and adrenaline was investigated in an isolated perfused pancreas preparation. PP was potently released by 1 nmol/l caerulein (186±12%, p〈0.001) and gastric inhibitory peptide (GIP) (211±31%, p〈0.005) as well as by 1 [νmol/l acetyl choline (1097±59%, p〈0.001). A significant two-fold release of PP was also evoked by 1 nmol/l vasoactive intestinal peptide (VIP) (129±38%, p〈0.02 and gastrin (108±25% p〈0.01). Insulin release, induced by high glucose concentration was enhanced by both GIP (210 ±38%, p〈(0.01) and VIP (48±5%, p〈0.001). In addition GIP enhanced the release of glucagon by 179±18% (p〈0.001) at 1.4 mmol/l glucose and by 127±24% (p〈0.005) at 8.3 mmol/l glucose. Thus no simple inter-relationship appears to exist between the control of the three circulating islet hormones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01228136
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  • 2
    Electronic Resource
    Electronic Resource
    Dual action of Mn++ upon the secretion of insulin and glucagon from the isolated, perfused canine pancreas (1978)
    Springer
    Diabetologia 15 (1978), S. 475-479 
    Details
    ISSN: 1432-0428
    Keywords: Manganese ; magnesium ; calcium ; insulin release ; glucagon release ; isolated ; perfused pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since Mn++ apparently interferes with excitation-contraction coupling by both reducing inward movement of Ca++ across the cell membrane and by displacing Ca++ from an intracellular store, studies were performed in the isolated, perfused canine pancreas to elucidate the existence of a similar effect in stimulus-secretion coupling and to draw comparisons with the effect of Mg++, which antagonizes Ca++ at the cell membrane. The results show: 1. that Mn++ (0.05, 0.125, and 0.25 mmol/l) inhibits the release of insulin and glucagon in a dose-dependent fashion during the first 3–4 min of infusion followed by a dose-dependent increase in hormone release, the ‘escape phase’. 2. The inhibitory action of Mn++ (0.25 mmol/l) upon release of both hormones is progressively counteracted when perfusate calcium is increased from 0.7 to 1.3 to 5.0 mmol/l. 3. Mg++ (5 mmol/l) inhibits the release of both hormones with no sign of an ‘escape phase’. 4. Mn++ (0.5 mmol/l) during calcium depletion causes a gradual stimulation of the release of both hormones. The dual action of Mn++ upon hormone release from the endocrine pancreas suggests that Mn++ can cross the cell membrane and can interfere with stimulus-secretion coupling both at the membrane level, by competitively inhibiting the Ca++ influx, and at some intracellular level by releasing calcium from an intracellular store.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02342873
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  • 3
    Electronic Resource
    Electronic Resource
    Streptozotocin diabetes: A glucoreceptor dysfunction affecting D cells as well as B and A cells (1979)
    Springer
    Diabetologia 17 (1979), S. 385-389 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes ; streptozotocin ; somatostatin release ; glucagon release ; isolated canine perfused pancreas ; glucoreceptor ; glucose ; arginine ; isoproterenol ; calcium ; radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Somatostatin release from the isolated pancreas of 3 normal and 6 streptozotocin diabetic dogs has been measured in response to various stimuli to determine whether abnormalities in somatostatin release are present in the diabetic pancreas. Simultaneous measurement of glucagon secretion was also made. In the pancreas from normal dogs increases in perfusate glucose from 25 to 200 mg/100 ml induced a 2–3 fold increase in somatostatin release and a two thirds decrease in glucagon secretion. In contrast, in the diabetic pancreas glucose caused no change in the secretion of the two hormones. In the diabetic pancreas addition of insulin to the perfusate (25,000 μU/ml) for periods from 10 to 75 minutes aimed at restoring normal extracellular insulin levels in the islets failed to restore either somatostatin or glucagon secretion to normal. In contradistinction to the lack of effect of glucose, the somatostatin and glucagon responses to arginine (5 mmol/l), isoproterenol (2 ng/ml) and calcium (5 mmol/l) were normal in the diabetic pancreas. The data suggests the presence of a selective glucoreceptor abnormality of the D as well as of B and A cells in the streptozotocin diabetic dog.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01236274
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  • 4
    Electronic Resource
    Electronic Resource
    Characterisation of somatostatin release from the pancreas (1979)
    Springer
    Diabetologia 16 (1979), S. 261-266 
    Details
    ISSN: 1432-0428
    Keywords: Perfused pancreas ; somatostatin ; insulin ; glucagon ; calcium ; acetylcholine ; glucose ; isoproterenol ; arginine ; radioimmunoassay ; dog pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of calcium on somatostatin secretion was investigated in the isolated, perfused canine pancreas preparation and compared with those of acetylcholine, glucose, isoproterenol and arginine. Calcium (5 mmol/l) stimulated somatostatin release in a typical biphasic response pattern being about 5 times as potent as acetylcholine (1 μmol/l), arginine (5 mmol/l), and isoproterenol (2 ng/ml) while the release of insulin and glucagon in response to calcium and the other secretagogues were of the same magnitude. Somatostatin release increased progressively when perfusate calcium was increased step-wise from 0 through 1.25 and 2.5 to 5.0 mmol/l. Calcium stimulated the secretion of somatostatin in the absence of glucose. The stimulatory effect of calcium was, however, modulated by the glucose concentration being about twice as large at 200 mg/100 ml as at 25 mg/100 ml glucose in the perfusion medium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01221953
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  • 5
    Electronic Resource
    Electronic Resource
    Secretion of somatostatin from the normal and diabetic pancreas (1980)
    Springer
    Diabetologia 19 (1980), S. 492-504 
    Details
    ISSN: 1432-0428
    Keywords: Pancreas ; dog pancreas ; diabetes ; somatostatin ; isolated perfused pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusions The role of cyclic AMP in the control of somatostatin release may be primarily that of a modulator without being an essential factor for initiation of somatostatin release. Much work is, however, still required to elucidate the exact nature of the role of cyclic AMP in the secretory mechanism of the D cell. All of the present evidence, however, points to a key regulatory role for calcium in the cascade of events that proceeds to the somatostatin secretion [24, 26, 30–33]. The data indicate that the changes in somatostatin secretion provoked by alterations in the extra-and intracellular levels of Na+ and K+ are secondary to changes in the intracellular level of calcium in the D cell. Caution should, however, be exercised in deducing from the results from cation fluxes in whole islets because of the mixed cell population studied. They cannot be assumed to represent the responses of the D cell alone because these cells make up only 5–15% of the total cell mass in the islet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253175
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  • 6
    Electronic Resource
    Electronic Resource
    Early recognition of autonomic dysfunction in microalbuminuria: significance for cardiovascular mortality in diabetes mellitus? (1994)
    Springer
    Diabetologia 37 (1994), S. 788-796 
    Details
    ISSN: 1432-0428
    Keywords: Key words Autonomic function, diabetes mellitus, 24-h heart rate variability, microalbuminuria, sudden cardiac death, vagal function, autonomic neuropathy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The appearance of microalbuminuria in diabetic patients predicts development of macroalbuminuria and coronary heart disease. Autonomic dysfunction in ischaemic heart disease is related to an increased incidence of arrhythmic deaths. To assess sympathovagal balance in relation to microalbuminuria we performed 24-h spectral analysis of RR interval oscillations in 37 insulin-dependent diabetic patients. Patients were divided according to urinary albumin excretion as normo-(〈20 µg/min) (n =12), micro-(〉20 and 〈200 µg/min) (n =14) and macro-albuminuria (〉200 µg/min) (n =11). None had symptoms or signs of ischaemic heart disease at clinical examination or during stress testing. Fourteen matched healthy subjects served as controls. Overall RR interval variability was calculated as the 24-h standard deviation. The square root of power of the low-frequency (0.04–0.15 Hz) and high-frequency (0.15–0.40 Hz) component were considered indices of the sympathovagal interaction and vagal function, respectively. Patients with micro and macroalbuminuria had, compared to control subjects, significantly reduced 24-h standard deviation, a much smaller day/night difference in mean RR level and a significantly reduced amplitude of the low frequency and high frequency oscillations, which were even more reduced in macroalbuminuria. The differences in vagal function were also present after correction for mean RR level, and differences in physical training level and smoking. Insulin-dependent diabetic patients who develop microalbuminuria have significantly impaired vagal function and abnormal sympathovagal interaction, which is further deranged in macroalbuminuria. This early autonomic dysfunction may later contribute to a increased risk for sudden cardiac death. [Diabetologia (1994) 37: 788–796]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404336
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  • 7
    Electronic Resource
    Electronic Resource
    The insulinotropic effect of endothelin-1 is mediated by glucagon release from the islet alpha cells (1999)
    Springer
    Diabetologia 42 (1999), S. 1302-1307 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Endothelin-1 ; insulin secretion ; glucagon secretion ; flow cytometry ; alpha cell ; beta cell ; clonal cell line ; endothelin receptor ; gene expression.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The circulating concentrations of endothelin-1 (ET-1), a peptide derived from endothelium, are increased in hypertension and diabetes. Endothelin-1 has recently been shown to be an insulinotropic agent. The mechanism of action of endothelin-1 on the endocrine pancreas has not yet been clarified. Methods. We investigated the action of endothelin-1 on the insulin secretion, the binding of 125I-ET-1 to beta cells as well as its effects on purified beta and non-beta cells from normal rats. The expression of endothelin receptors in alpha- and beta-cell lines and in normal rat islets was also studied. Results. First, we studied the effects of endothelin-1 on insulin secretion from beta-cell lines (INS-1, βTC3 and MIN6). At all endothelin-1 concentrations applied (1 pmol/l to 1 μmol/l) no change in insulin secretion was found. Ligand-binding experiments on βTC3 cells showed no specific binding of 125I-ET-1. A prominent expression of ETA-receptor mRNA in an alpha-cell line (αTC1.9) and in normal rat islets was found whereas no expression was found in INS-1 cells. No influence of endothelin-1(1 μmol/l) on insulin secretion stimulated by glucose was detected from purified beta cells. Endothelin-1-(100 nmol/l) increased, however, both insulin and glucagon secretion from a mixture of purified beta and non-beta cells indicating that alpha cells seem to have a key role for the action of ET-1 on insulin secretion. Conclusion/interpretation. The insulinotropic impact of endothelin-1 is not caused by a direct action on the beta cells but seems to be mediated by a paracrine action, probably secondary to enhanced release of glucagon from the endothelin receptor positive alpha cells. [Diabetologia (1999) 42: 1302–1307]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051442
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  • 8
    Electronic Resource
    Electronic Resource
    Urinary albumin excretion rate and 24-h ambulatory blood pressure in NIDDM with microalbuminuria: effects of a monounsaturated-enriched diet (1995)
    Springer
    Diabetologia 38 (1995), S. 1069-1075 
    Details
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; microalbuminuria ; blood pressure ; monounsaturated fat diet ; olive oil ; diet ; metabolic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have shown that unsaturated fat-enriched diets may have a beneficial effect on blood pressure in non-insulin-dependent diabetic (NIDDM) patients, whereas little is known about the effects on albuminuria. In a 3-week cross-over design we compared the effects of a currently recommended high-carbohydrate diet (50% carbohydrate, 30% fat [10% monounsaturated fat]) vs a diet rich in monounsaturated fat (30% carbohydrate, 50% fat [30% monounsaturated fat]) on urinary albumin excretion rate, 24-h ambulatory blood pressure and metabolic control in ten NIDDM patients with persistent microalbuminuria. The 24-h ambulatory blood pressure was similar before and after both the high-carbohydrate diet (mean±SD: 145/78±25/10 vs 143/79±19/10 mmHg (NS) and the monounsaturated fat diet: 140/78±16/8 vs 143/79±15/8 mmHg (NS). No changes were observed in day or night-time blood pressures. Urinary albumin excretion rate was unaffected after 3 weeks' treatment by the diets: from (geometric mean ×/÷ tolerance factor) 32.4×/÷2.1 to 36.0×/÷1.9 Μg/min (NS) vs from 34.2×/÷1.9 to 32.1×/÷2.1 Μg/min (NS). Fasting plasma glucose, serum fructosamine and HbA1c as well as lipid and lipoprotein concentrations were stable during both diets. Compared to the high-carbohydrate diet a reduction in the LDL/HDL cholesterol ratio was observed during the monounsaturated fat diet (p〈0.03). In conclusion, compared to a high-carbohydrate diet, 3 weeks' treatment with a monounsaturated fat diet did not affect the levels of 24-h ambulatory blood pressure or albuminuria in microalbuminuric NIDDM patients. Moreover, glycaemic control and lipoprotein levels were unchanged, although a potential beneficial effect on the LDL/HDL-cholesterol ratio was noted. Monounsaturated fat represents an alternative in the diets of NIDDM patients especially when caloric intake is not a concern.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402177
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  • 9
    Electronic Resource
    Electronic Resource
    Endothelin-1 stimulates insulin secretion by direct action on the islets of Langerhans in mice (1996)
    Springer
    Diabetologia 39 (1996), S. 1030-1035 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Endothelin-1 ; islet of Langerhans ; mouse ; ion fluxes ; glucose ; insulin secretion.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor peptide, is secreted in response to insulin. Elevated circulating ET-1 levels have been found in patients with diabetes mellitus and vascular dysfunction. The question arises whether ET-1 acts as a direct modulator of insulin secretion. To test this, we studied the effects of ET-1 on isolated mouse islets of Langerhans. ET-1 (1 nmol/l–1 μmol/l) dose-dependently stimulated insulin secretion from islets incubated in the presence of 16.7 mmol/l glucose (p 〈 0.05). The effect of ET-1 is glucose-dependent since no potentiation was found at 3.3 mmol/l glucose. Furthermore, ET-1 induced a large, transient increase in glucose-stimulated insulin secretion during islet perifusion in the presence (p 〈 0.001), but not in the absence, of extracellular Ca2 + . The rate of 45Ca2 + -efflux from 45Ca2 + -prelabelled islets was transiently stimulated by ET-1 during perifusion at 16.7 mmol/l glucose in the presence of extracellular Ca2 + (p 〈 0.001). A short-lived increase in 45Ca2 + -efflux was also observed in the absence of extracellular Ca2 + (p 〈 0.05). It is suggested that the effects of ET-1 on insulin secretion are critically dependent on influx via Ca2 + -channels. In addition, ET-1 transiently enhanced 86Rb + -efflux from 86Rb + -prelabelled islets both in the presence (p 〈 0.001) and in the absence (p 〈 0.001) of extracellular Ca2 + suggesting that ET-1 does not elicit insulin secretion by inhibition of the potassium permeability. Our study provides evidence that ET-1 stimulates insulin secretion via a direct effect on the islets of Langerhans. [Diabetologia (1996) 39: 1030–1035]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400650
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  • 10
    Electronic Resource
    Electronic Resource
    Urinary albumin excretion rate and 24-h ambulatory blood pressure in NIDDM with microalbuminuria: effects of a monounsaturated-enriched diet (1995)
    Springer
    Diabetologia 38 (1995), S. 1069-1075 
    Details
    ISSN: 1432-0428
    Keywords: Key words Non-insulin-dependent diabetes mellitus; microalbuminuria ; blood pressure ; monounsaturated fat diet ; olive oil ; diet ; metabolic control.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have shown that unsaturated fat-enriched diets may have a beneficial effect on blood pressure in non-insulin-dependent diabetic (NIDDM) patients, whereas little is known about the effects on albuminuria. In a 3-week cross-over design we compared the effects of a currently recommended high-carbohydrate diet (50 % carbohydrate, 30 % fat [10 % monounsaturated fat]) vs a diet rich in monounsaturated fat (30 % carbohydrate, 50 % fat [30 % monounsaturated fat]) on urinary albumin excretion rate, 24-h ambulatory blood pressure and metabolic control in ten NIDDM patients with persistent microalbuminuria. The 24-h ambulatory blood pressure was similar before and after both the high-carbohydrate diet (mean ± SD: 145/78 ± 25/10 vs 143/79 ± 19/10 mmHg (NS) and the monounsaturated fat diet: 140/78 ± 16/8 vs 143/79 ± 15/8 mmHg (NS). No changes were observed in day or night-time blood pressures. Urinary albumin excretion rate was unaffected after 3 weeks' treatment by the diets: from (geometric mean ×/7 tolerance factor) 32.4 ×/72.1 to 36.0 ×/7 1.9 μg/min (NS) vs from 34.2 ×/7 1.9 to 32.1 ×/7 2.1 μg/min (NS). Fasting plasma glucose, serum fructosamine and HbA1c as well as lipid and lipoprotein concentrations were stable during both diets. Compared to the high-carbohydrate diet a reduction in the LDL/HDL cholesterol ratio was observed during the monounsaturated fat diet (p 〈 0.03). In conclusion, compared to a high-carbohydrate diet, 3 weeks' treatment with a monounsaturated fat diet did not affect the levels of 24-h ambulatory blood pressure or albuminuria in microalbuminuric NIDDM patients. Moreover, glycaemic control and lipoprotein levels were unchanged, although a potential beneficial effect on the LDL/HDL-cholesterol ratio was noted. Monounsaturated fat represents an alternative in the diets of NIDDM patients especially when caloric intake is not a concern. [Diabetologia (1995) 38: 1069–1075]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402177
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