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  • Key words Non-insulin-dependent diabetes mellitus  (3)
  • Patch clamp  (3)
  • fetal growth  (3)
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    The journal of membrane biology 145 (1995), S. 267-278 
    ISSN: 1432-1424
    Schlagwort(e): Rat insulinoma cell line, CRI-G1 ; Cyclic nucleotide regulation ; Calcium-activated nonselective cation channel ; Patch clamp
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The regulation of a calcium-activated nonselective cation (Ca-NS+) channel by analogues of cyclic AMP has been investigated in the rat insulinoma cell line, CRI-G1. The activity of the channel is modulated by cyclic AMP in a complex way. In the majority of patches (83%) tested concentrations of cyclic AMP of 10 μm and above cause an inhibition of channel activity which is immediately reversible on washing. In contrast, lower concentrations of cyclic AMP, between 0.1 and 1.0 μm, produce a transient activation of channel activity in most patches (63%) tested. One group of analogues, including N6-monobutyryl cyclic AMP and N6, 2′-O-dibutyryl cyclic AMP reduced the activity of the Ca-NS+ channel at all concentrations tested and 2′-O-Monobutyryl cyclic AMP produced inhibition in all patches tested except one, at all concentrations. A second group produced dual concentration-dependent effects on Ca-NS+, low concentrations stimulating and high concentrations inhibiting channel activity. 6-Chloropurine cyclic AMP and 8-bromo cyclic AMP produced effects similar to those of cyclic AMP itself. In contrast, 8-[4-chlorophenylthio] cyclic AMP also showed a dual action, but with a high level of activation at all concentrations tested up to 1mm. Ca-NS+ channel activity was also predominantly activated by low concentrations of Sp-cAMPS. The activating effects of both Sp-cAMPS and cyclic AMP are antagonized by Rp-cAMPS, which by itself only produced a weak inhibition of Ca-NS+ channel activity even at concentrations of 10 μm and above. The results are discussed in terms of a model in which cyclic AMP, and other cyclic nucleotides, modulate the activity of the Ca-NS+ channel by binding to two separate sites.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    The journal of membrane biology 141 (1994), S. 101-112 
    ISSN: 1432-1424
    Schlagwort(e): Rat insulinoma cell line ; CRI-G1 ; Nucleotide regulation ; Calcium-activated nonselective cation channel ; Patch clamp
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The nucleotide regulation of a calcium-activated nonselective cation (Ca-NS+) channel has been investigated in the rat insulinoma cell line CRI-G1. The activity of the channel is reduced by both AMP and ADP (1–100 μm) in a concentration-dependent manner, with AMP being more potent than ADP. At lower concentrations (0.1–5 μm), both ADP and AMP activate the channel in some patches. Examination of the nucleotide specificity of channel inhibition indicates a high selectivity for AMP over the other nucleotides tested with a rank order of potency of AMP 〉 UMP 〉 CMP ≥GMP. Cyclic nucleotides also modulate channel activity in a complex, concentration-dependent way. Cyclic AMP exhibits a dual effect, predominantly increasing channel activity at low concentrations (0.1–10 μm) and reducing it at higher concentrations (100 μm and 1 mm). Specificity studies indicate that the cyclic nucleotide site mediating inhibition of channel activity exhibits a strong preference for cyclic AMP over cyclic GMP, with cyclic UMP being almost equipotent with cyclic AMP. Cyclic IMP and cyclic CMP are not active at this site. The cyclic nucleotide site mediating activation of the channel shows much less nucleotide specificity than the inhibitory site, with cyclic AMP, cyclic GMP and cyclic IMP being almost equally active.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 37 (1994), S. 592-596 
    ISSN: 1432-0428
    Schlagwort(e): NIDDM ; insulin secretion ; fetal growth ; programming
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Recent studies suggest that NIDDM is linked with reduced fetal and infant growth. Observations on malnourished infants and studies of experimental animals exposed to protein energy or protein deficiency in fetal or early neonatal life suggest that the basis of this link could lie in the detrimental effects of poor early nutrition on the development of the beta cells of the islets of Langerhans. To test this hypothesis we have measured insulin secretion following an IVGTT in a sample of 82 normoglycaemic and 23 glucose intolerant subjects who were born in Preston, England, and whose birthweight and body size had been recorded at birth. The subjects with impaired glucose tolerance had lower first phase insulin secretion than the normoglycaemic subjects (mean plasma insulin concentrations 3 min after intravenous glucose 416 vs 564 pmol/l, p=0.04). Insulin secretion was higher in men than women (601 vs 457 pmol/l, P=0.02) and correlated with fasting insulin level (p=0.04). However, there was no relationship between insulin secretion and the measurements of prenatal growth in either the normoglycaemic or glucose intolerant subjects. These results argue against a major role for defective insulin secretion as a cause of glucose intolerance in adults who were growth retarded in pre-natal life.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1432-0428
    Schlagwort(e): Keywords Insulin resistance ; fetal growth ; non-insulin-dependent diabetes mellitus ; desaturase activity.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Numerous studies show an association between poor fetal growth and adult insulin resistance. Recent studies have shown relation between the long chain polyunsaturated fatty acid composition of skeletal muscle membranes and insulin sensitivity. More detailed analysis has indicated that the activity of Δ5 desaturase is inversely correlated to insulin resistance. The amount of docosahexaenoic acid (C22:6n3) is also thought to play a part in determining insulin sensitivity. The purpose of this study was to test the hypothesis that early growth retardation in the rat, as a result of maternal protein restriction, would lead to alterations in desaturase activities similar to those observed in human insulin resistance. There were no differences in phospholipid fatty acid composition in liver or muscle from control and low protein rats. In both muscle and liver the ratio of docosahexaenoic acid to docosapentaenoic acid was, however, reduced in low protein offspring. Direct measurement of Δ5 desaturase activity in hepatic microsomes showed a reduction (p 〈 0.03) in the low protein offspring which was negatively corrrelated (r = – 0.855) with fasting plasma insulin. No correlation was observed in controls. These results show that it is possible to programme the activity of key enzymes involved in the desaturation of long chain polyunsaturated fatty acids. This is possibly a mechanism linking fetal growth retardation to insulin resistance. [Diabetologia (1998) 41: 1337–1342]
    Materialart: Digitale Medien
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  • 5
    ISSN: 1432-0428
    Schlagwort(e): Key words Non-insulin-dependent diabetes mellitus ; vitamin D ; vitamin D deficiency ; total insulin ; specific insulin ; proinsulin ; 32 ; 33 split proinsulin ; C-peptide ; glucose intolerance.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Vitamin D deficiency reduces insulin secretion and still occurs in East London Asians in whom the prevalence of diabetes mellitus is at least four times that of Caucasians. Vitamin D status was assessed in 44 of 65 non-diabetic subjects ’at risk' of diabetes (spot blood glucose level 〉 6.0 mmol/l 〈 2 h post cibum, or 〉 4.6 mmol/l 〉 2 h post cibum on two separate occasions) and in 15 of 60 age and sex-matched ’low-risk' control subjects who attended for oral glucose tolerance test (OGTT) after screening of 877 omnivorous subjects not known to have diabetes. It was found that 95 % of at-risk and 80 % of low-risk subjects were vitamin D deficient (serum 25-hydroxy-vitamin D 〈 11 ng/ml). Diabetes was present in 16, impaired glucose tolerance in 12 and normoglycaemia in 19 at-risk subjects, impaired glucose tolerance in 2, and normoglycaemia in 13 low-risk subjects. Correlations of 30-min OGTT blood glucose, specific insulin and C-peptide levels with 25-hydroxy-vitamin D concentrations in 44 at-risk subjects were −0.31 (p = 0.04), 0.59 (p = 0.0001) and 0.44 (p = 0.006). In 15 ’not-at-risk' subjects 30-min OGTT specific insulin and C-peptide levels correlated with 25-hydroxy-vitamin D, r = 0.39 (p = 0.04) and 0.16 (p = 0.43), respectively. Serum alkaline phosphatase concentration was higher in at-risk than not-at-risk subjects (59.6 vs 46.5 IU/l, p = 0.012); corrected calcium concentrations were comparable (2.38 vs 2.39 mmol/l, p = 0.7). Following treatment with 100,000 IU vitamin D by i. m. injection, specific insulin, C-peptide [30 min on OGTT] and 25-hydroxy-vitamin D concentrations had risen 8–12 weeks later [means ± SD] from 57 ± 62 to 96.2 ± 82.4 mU/l [p = 0.0017], 1.0 ± 0.4 to 1.7 ± 0.8 pmol/ml [p = 0.0001] and 3.6 ± 1.8 to 13.5 ± 7.4 ng/ml [p = 0.0001], (but not to low-risk group values of 179 ± 89 mU/l, 2.7 ± 1.14 pmol/ml and 8.16 ± 6.4 ng/ml), respectively. Both total serum alkaline phosphatase and corrected calcium concentrations rose following vitamin D treatment in the at-risk subjects by 11.1 ± 8.22 (from 44 to 55 IU/l) and 0.15 ± 0.18, (2.43 to 2.57 mmol/l), respectively (p = 0.004). Abnormal glucose tolerance was unchanged by vitamin D treatment. The value of early and sustained repletion with vitamin D in diabetes prophylaxis should be examined in communities where vitamin D depletion is common. [Diabetologia (1995) 38: 1239–1245]
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-0428
    Schlagwort(e): Key words Non-insulin-dependent diabetes mellitus ; insulin ; sulphonylurea receptors ; islets ; glibenclamide ; secretory granule.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Sulphonylureas stimulate insulin secretion by binding to a receptor in the pancreatic beta-cell plasma membrane resulting in inhibition of ATP-sensitive K+ channels, membrane depolarization and thus influx of Ca2+ through voltage-dependent Ca2+ channels. Sulphonylureas can also induce hormone release at fixed membrane potentials without Ca2+ entry suggesting that these drugs may have other modes of action. We have determined whether different forms of sulphonylurea-binding proteins are present in insulin-secreting cells and their subcellular localization by density gradient centrifugation. Binding studies using [3H]-glibenclamide showed that islet and insulinoma membranes contained a single high affinity sulphonylurea binding site (Kd = 1 nmol/l). Photo-crosslinking of the drug to the membranes resulted in labelling of two proteins with apparent molecular weights of 170 and 140 kDa. The same analyses of insulinoma subcellular fractions showed that the majority ( 〉 90 %) of binding proteins were localized to intracellular membranes with only minor levels ( 〈 10 %) on plasma membranes. The 170 kDa sulphonylurea binding protein was present in both plasma and granule membrane fractions whereas the 140 kDa form was not present in the plasma membrane fraction. The differences in the molecular forms and subcellular distribution of the receptor are consistent with sulphonylureas having multiple sites of action in the pancreatic beta cell. [Diabetologia (1995) 38: 277–282]
    Materialart: Digitale Medien
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  • 7
    ISSN: 1432-0428
    Schlagwort(e): Impaired glucose tolerance ; non-insulin-dependent diabetes mellitus ; fetal growth ; ponderal index at birth ; placental weight to birthweight ratio
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary A follow-up study was carried out to determine whether reduced fetal growth is associated with the development of impaired glucose tolerance in men and women aged 50 years. Standard oral glucose tolerance tests were carried out on 140 men and 126 women born in Preston (Lancashire, UK) between 1935 and 1943, whose size at birth had been measured in detail. Those subjects found to have impaired glucose tolerance or non-insulin-dependent diabetes mellitus had lower birthweight, a smaller head circumference and were thinner at birth. They also had a higher ratio of placental weight to birthweight. The prevalence of impaired glucose tolerance or diabetes fell from 27% in subjects who weighed 2.50 kg (5.5 pounds) or less at birth to 6% in those who weighed more than 3.41 kg (7.5 pounds) (p 〈 0.002 after adjusting for body mass index). Plasma glucose concentrations taken at 2-h in the glucose tolerance test fell progressively as birthweight increased (p 〈 0.004), as did 2-h plasma insulin concentrations (p 〈 0.001). The trends with birthweight were independent of duration of gestation and must therefore be related to reduced rates of fetal growth. These findings confirm the association between impaired glucose tolerance in adult life and low birthweight previously reported in Hertfordshire (UK), and demonstrate it in women as well as men. It is suggested that the association reflects the long-term effects of reduced growth of the endocrine pancreas and other tissues in utero. This may be a consequence of maternal undernutrition.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1432-0428
    Schlagwort(e): Key words Non-insulin-dependent diabetes mellitus ; impaired glucose tolerance ; hypertriglyceridaemia ; hyperinsulinaemia ; non-esterified fatty acid.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Although plasma insulin and triglyceride concentrations are positively correlated in many studies, the relationships between insulin resistance, insulin secretion and hypertriglyceridaemia remain unclear. To study these associations, subjects between the ages of 40 and 64 were randomly selected from a general practice register and invited to attend for a standard oral glucose tolerance test for measurement of insulin, triglyceride and non-esterified fatty acid concentrations. The study comprised 1122 subjects who were not previously known to have diabetes and who completed the test. Using the World Health Organisation criteria, 51 subjects were classified to have non-insulin-dependent diabetes mellitus, 188 had impaired glucose tolerance and 883 subjects had normal glucose tolerance. Triglyceride concentrations in subjects with glucose intolerance were elevated compared to those in control subjects, even after adjustment for age, obesity and gender (p 〈 0.001 for subjects with diabetes and p 〈 0.01 for those with impaired glucose tolerance compared to normal subjects). In separate multiple regression analyses for males and females, the most important determinants of the plasma triglyceride concentration were the area under the non-esterified fatty acid suppression curve (p 〈 0.001 in both genders) and the waist-hip ratio (p 〈 0.001 for men and 〈 0.01 for women). The fasting insulin concentration was independently associated with triglyceride concentration in women only (p 〈 0.01). The most important determinant of the area under the non-esterified fatty acid suppression curve in men was the 30-min insulin increment, a measure of insulin secretion, (p 〈 0.001) whereas for women age (p 〈 0.001) and the body mass index (p 〈 0.01) were the most important. [Diabetologia (1994) 37: 889–896]
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 409 (1987), S. 607-615 
    ISSN: 1432-2013
    Schlagwort(e): Insulinoma cell line ; Patch clamp ; Cation channel ; Calcium dependence ; ATP sensitive
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A calcium-acivated non-selective cation channel was observed in isolated plasma membrane patches from an insulin-secreting cell line (CRI-Gl). The conductance of the channel was approximately 25 pS with identical (140 mM KCl) solutions on either side of the membrane. However, some rectification was observed (smaller outward current) when sodium ions were present extracellularly. The channel was inactive on exposure to an intracellular calcium concentration of 10−6 M and required high (greater than 10−4 M) concentrations for a significant degree of activation. The open-state probability of the channel was voltage dependent, increasing with membrane depolarization. Analysis of single channel kinetics indicated that there were at least two open and two closed states. Application of ATP to the cytoplasmic membrane surface reduced the open state probability in a dose-dependent manner. The channel activity was blocked by quinine and 4-AP but was insensitive to TEA, TTX and amiloride. It is not clear what role this channel might play in the complex electrical activity of β-cells.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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