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  • 1
    ISSN: 1432-0428
    Keywords: Islet amyloid polypeptide ; amylin ; insulin ; dexamethasone ; rat ; pancreatic islets ; in situ hybridization ; gene expression ; mRNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Islet amyloid polypeptide (IAPP), a novel islet hormone candidate, has been reported to be over-expressed relative to insulin in rats following dexamethasone treatment. In order to investigate the expression of IAPP and insulin following dexamethasone treatment of rats for 12 days, we applied in situ hybridization and immunocytochemistry, allowing us to evaluate islet changes in gene expression and morphology. Tissue concentrations of IAPP and insulin were measured by radioimmunoassay. A low dose of dexamethasone (0.2 mg/kg daily) increased the islet levels of IAPP and insulin mRNA to 249±13% and 150±24% of controls, respectively (p〈0.001 and p〈0.01). A high dose of dexamethasone (2.0 mg/kg daily) increased the islet levels of IAPP and insulin mRNA to 490±13% and 203±9% of controls, respectively (p〈0.001 and p〈0.001). The pancreatic concentration of IAPP increased more than that of insulin (p〈0.05). Morphometric analysis revealed that dexamethasone treatment induced both hyperplasia and hypertrophy of insulin cells. Changes in the cellular localization of IAPP and insulin mRNA were not observed. Thus, we conclude that the increased level of IAPP mRNA is due to both an increase at the cellular level as well as hyperplasia/hypertrophy of insulin cells. In contrast, the increased level of insulin mRNA appears to be due to hyperplasia/hypertrophy of insulin cells, since insulin gene expression decreased at the cellular level (p〈0.001 vs controls). These observations provide further evidence that IAPP and insulin gene expression are regulated in a non-parallel fashion, which may be relevant to the pathogenesis of non-insulin-dependent diabetes mellitus
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 38 (1995), S. 47-47 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Key words Islet amyloid polypeptide ; amylin ; insulin ; dexamethasone ; rat ; pancreatic islets ; in situ hybridization ; gene expression ; mRNA.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Islet amyloid polypeptide (IAPP), a novel islet hormone candidate, has been reported to be over-expressed relative to insulin in rats following dexamethasone treatment. In order to investigate the expression of IAPP and insulin following dexamethasone treatment of rats for 12 days, we applied in situ hybridization and immunocytochemistry, allowing us to evaluate islet changes in gene expression and morphology. Tissue concentrations of IAPP and insulin were measured by radioimmunoassay. A low dose of dexamethasone (0.2 mg/kg daily) increased the islet levels of IAPP and insulin mRNA to 249 ± 13 % and 150 ± 24 % of controls, respectively (p 〈 0.001 and p 〈 0.01). A high dose of dexamethasone (2.0 mg/kg daily) increased the islet levels of IAPP and insulin mRNA to 490 ± 13 % and 203 ± 9 % of controls, respectively (p 〈 0.001 and p 〈 0.001). The pancreatic concentration of IAPP increased more than that of insulin (p 〈 0.05). Morphometric analysis revealed that dexamethasone treatment induced both hyperplasia and hypertrophy of insulin cells. Changes in the cellular localization of IAPP and insulin mRNA were not observed. Thus, we conclude that the increased level of IAPP mRNA is due to both an increase at the cellular level as well as hyperplasia/hypertrophy of insulin cells. In contrast, the increased level of insulin mRNA appears to be due to hyperplasia/hypertrophy of insulin cells, since insulin gene expression decreased at the cellular level (p 〈 0.001 vs controls). These observations provide further evidence that IAPP and insulin gene expression are regulated in a non-parallel fashion, which may be relevant to the pathogenesis of non-insulin-dependent diabetes mellitus [Diabetologia (1995) 38: 395–402]
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 380 (1995), S. 119-124 
    ISSN: 1435-2451
    Keywords: Primärer Hyperparathyreoidismus PTH ; Immunheterogenität Kalzium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei primärem Hyperparathyreoidismus (pHPT) kann, wie man weiβß, eine Freisetzung eher von intaktem PTH (i-PTH) als von Fragmenten mit end-ständigen Carboxylgruppen erfolgen. Wir untersuchten, ob die Freisetzung von PTH-Fragmenten mit terminalen Aminogruppen (N-PTH) sich ebenfalls ändert. Es wurden die Serumspiegel von i-PTH und N-PTH unter folgenden Bedingungen bestimmt: (1) bei 6 pHPT-Patienten (a) ohne Kalziumgabe, (b) nach oraler Kalziumgabe vor und unmittelbar nach Operation und (2) bei 7 gesunden Personen. Bei ersteren waren präoperativ beide Spiegel — i-PTH und N-PTH — erhöht, die i-PTH-Spiegel etwas stärker. Daher war das Verhältnis N-PTH/i-PTH im Vergleich zu gesunden Personen vermindert (p〈0,05). Postoperativ war am 1. Tag das Serum-i-PTH stärker vermindert als das N-PTH, wodurch das N-PTH/i-PTH-Verhältnis gegenüber Gesunden zunahm (p〈0,05); am 5. Tag normalisierte sich dieses Verhältnis. Präoperativ verbesserte sich die Supprimierung von i-PTH-Kalzium bei den Patienten, während die Supprimierung von N-PTH-Kalzium normal blieb, was seinen Ausdruck fand in einem unveränderten N-PTH/i-PTH-Verhältnis während der oralen Kalziumeinnahme. Im Gegensatz dazu vergrößerte sich das N-PTH/i-PTH-Verhältnis in normaler Weise während der Kalziumeinnahme am 5. Tag postoperativ (p〈0,05). Schlußfolgerungen: (1) Bei pHPT ändert sich die zirkulierende PTH-Immunheterogenität mit einer vorzugsweisen Freisetzung von i-PTH im Vergleich zu N-PTH, und diese Veränderung normalisiert sich nach Operation. (2) Die Sekretion von i-PTH und N-PTH zeigt unterschiedliche Sensitivität gegenüber einer Inhibierung durch Kalzium.
    Notes: Abstract In primary hyperparathyroidism (pHPT), a preferential release of intact PTH (i-PTH) versus carboxyl-terminal PTH fragments is known to occur. We studied whether the release of amino-terminal PTH fragments (N-PTH) is also changed. Serum levels of i-PTH and N-PTH were determined under basal conditions and following oral intake of calcium in six patients with pHPT before and immediately after surgery and in seven healthy subjects. In the patients, baseline levels of both i-PTH and N-PTH were increased preoperatively. The increase was larger in i-PTH compared to N-PTH. Therefore, the N/i ratio was reduced compared to healthy subjects (P〈0.05). On the first postoperative day, serum i-PTH decreased to a larger extent than N-PTH, which increased the N/i ratio above that in healthy subjects (P〈 0.05). On the 5th postoperative day, the N/i ratio was normalized. Preoperatively, the suppressibility of i-PTH calcium was impaired in the patients (P〈0.05), whereas the suppressibility of N-PTH was normal, resulting in unchanged N/i ratio during the oral calcium load. In contrast, the N/i ratio increased normally during the calcium load at day 5 postoperatively (P〈0.05). We therefore conclude that: (1) in pHPT, circulating PTH immunoheterogeneity is altered with a preferential release of intact PTH compared to N-terminal PTH fragments and this alteration is normalized after surgery, (2) the secretion of intact PTH and N-terminal PTH shows different sensitivity to inhibition by calcium.
    Type of Medium: Electronic Resource
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