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  • 1
    ISSN: 1432-0428
    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.
    Type of Medium: Electronic Resource
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  • 2
    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
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  • 3
    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
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  • 4
    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
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  • 5
    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
    Library Location Call Number Volume/Issue/Year Availability
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