| Autor: |
Rochlitz, H., Voigt, A., Lankat-Buttgereit, B., Göke, B., Heimberg, H., Nauck, M. A., Schiemann, U., Schatz, H., Pfeiffer, A. F. H. |
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| Zdroj: |
Diabetologia; Apr2000, Vol. 43 Issue 4, p465-473, 9p |
| Abstrakt: |
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 IIβ and the kinase domain of CaMK IIδ 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 IIβ-mRNA. In human beta cells CaMK IIβ and δ were expressed equally with pyruvate dehydrogenase whereas tenfold lower expression of CaMK IIγ and no expression of CaMK IIα were found.¶Conclusion/interpretation. Although CaMK IIδ is ubiquitously expressed, CaMK IIβ 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] [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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