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  • 1
    ISSN: 1432-0428
    Keywords: Keywords Insulin secretion, protein kinase, insulin secreting cells, human CaMK II, cloning of new subtypes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The Ca2+/calmodulin-dependent protein kinase II (CaMK II) is highly expressed in pancreatic islets and associated with insulin secretion vesicles. The suppression of CaMK II disturbs insulin secretion and insulin gene expression. There are four isoforms of CaMK II, α to δ, that are expressed from different genes in mammals. Our aim was to identify the isoforms of CaMK II expressed in human beta cells by molecular cloning from a human insulinoma cDNA library and to assess its distribution in humans.¶Methods. The previously unknown complete coding sequences of human CaMK II β and the kinase domain of CaMK II δ were cloned from a human insulinoma cDNA library. Quantitative determination of CaMK II isoform mRNA was carried out in several tissues and beta cells purified by fluorescence activated cell sorting and compared to the housekeeping enzyme pyruvate dehydrogenase.¶Results. We found CaMK IIβ occurred in three splice variants and was highly expressed in endocrine tissues such as adrenals, pituitary and beta cells. Liver showed moderate expression but adipose tissue or lymphocytes had very low levels of CaMK II β-mRNA. In human beta cells CaMK II β and δ were expressed equally with pyruvate dehydrogenase whereas tenfold lower expression of CaMK II γ and no expression of CaMK IIα were found.¶Conclusion/interpretation. Although CaMK II δ is ubiquitously expressed, CaMK II β shows preferential expression in neuroendocrine tissues. In comparison with the expression of a key regulatory enzyme in glucose oxidation, pyruvate dehydrogenase, two of the four CaM kinases investigated are expressed at equally high levels, which supports an important role in beta-cell physiology. These results provide the basis for exploring the pathophysiological relevance of CaMK IIβ in human diabetes. [Diabetologia (2000) 43: 465–473]
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 595 (1990), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1360-0443
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
    Notes: Aim  To test the clinical performance of carbohydrate-deficient transferrin (%CDT), γ-glutamyltransferase (γ-GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for alcoholism with a special focus on patients suffering from liver diseases.Design  Well-characterized collectives of alcohol-dependent patients with current consumption (ALC patients, n = 101), and relevant control groups (115 social drinkers, 46 patients with unspecifically increased γ-GT, 51 hepatitis patients and 20/31 patients with non-alcohol/alcohol-dependent liver cirrhosis) were included into the study. The Positive Alcohol Use Disorders Test (AUDIT) score, International Classification of Diseases version 10 (ICD-10)/Diagnostic and Statistical Manual version IV (DSM-IV) criteria and blood drawn within 4 days of last drinking were inclusion criteria for subjects with regular heavy drinking. %CDT was determined using an automated assay which recently had been completely modified.Findings  Median AUDIT scores of patients without/with regular heavy drinking were 1–3/27. The following medians/95th percentiles were obtained for %CDT: social drinkers 2.2/3.0, patients with unspecifically increased γ-GT 2.1/3.0, hepatitis 2.0/4.4, non-alcohol-dependent liver cirrhosis 2.4/4.8, alcohol-dependent liver cirrhosis 3.0/5.9, ALC patients 3.9/14.9. Differences between patients without and with alcohol abuse were highly significant (P 〈 0.001). No differences in CDT values were found between males and females. There was no correlation between %CDT values, γ-GT, MCV and the amount of alcohol consumed in ALC patients; 3.0%CDT (95th percentile social drinkers) is proposed as cut-off for the test used (Tina-quant®%CDT 2nd-generation). At this cut-off, the sensitivity for ALC patients was 73.3%, whereas γ-GT/MCV had a sensitivity of 71.3%/64.4%. Multivariate analysis performed at 95% specificity resulted in an improvement of the sensitivity by combining %CDT with γ-GT (83.2%). A further enhancement of the sensitivity to 88.1% was obtained by combination of %CDT, γ-GT and MCV. The diagnostic specificity of %CDT calculated at the cut-off of 3% was 93.5% in patients with unspecifically increased γ-GT, 88.2% in hepatitis patients and 70.0% in patients with non-alcohol-dependent liver cirrhosis. %CDT was more specific in these patient collectives than MCV, and especially more than γ-GT (specificity in hepatitis 52.9%, and 35.0% in non-alcohol-dependent liver cirrhosis).Conclusion  %CDT is of high diagnostic value to support diagnosis of alcohol-use disorders. The specificity of this marker in patient groups with liver disorders is superior to the biomarkers γ-GT and MCV.
    Type of Medium: Electronic Resource
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