caa a22 4500 475772415 CHVBK 20180406123621.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1007/s001250051330 doi (NATIONALLICENCE)springer-10.1007/s001250051330 Cloning and quantitative determination of the human Ca2+/calmodulin-dependent protein kinase II (CaMK II) isoforms in human beta cells [Elektronische Daten] [H. Rochlitz, A. Voigt, B. Lankat-Buttgereit, B. Göke, H. Heimberg, M. A. Nauck, U. Schiemann, H. Schatz, A. F. H. Pfeiffer] 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] Springer-Verlag Berlin Heidelberg, 2000 Keywords Insulin secretion, protein kinase, insulin secreting cells, human CaMK II, cloning of new subtypes nationallicence Rochlitz H. Department of Internal Medicine, University Hospital Bergmannsheil, University of Bochum, Bochum, Germany, DE aut Voigt A. Department of Internal Medicine, University Hospital Bergmannsheil, University of Bochum, Bochum, Germany, DE aut Lankat-Buttgereit B. Clinical Research Unit for Gastrointestinal Endocrinology, Department of Internal Medicine, Philipps-University of Marburg, Marburg, Germany, DE aut Göke B. Clinical Research Unit for Gastrointestinal Endocrinology, Department of Internal Medicine, Philipps-University of Marburg, Marburg, Germany, DE aut Heimberg H. Diabetes Research Centre, Vrije Universiteit Brussels, Brussels, Belgium, BE aut Nauck M. A. Department of Internal Medicine, Knappschafts Hospital, University of Bochum, Bochum, Germany, DE aut Schiemann U. Department of Internal Medicine B, University Hospital of Münster, Münster, Germany, DE aut Schatz H. Department of Internal Medicine, University Hospital Bergmannsheil, University of Bochum, Bochum, Germany, DE aut Pfeiffer A. F. H. Department of Internal Medicine, University Hospital Bergmannsheil, University of Bochum, Bochum, Germany, DE aut https://doi.org/10.1007/s001250051330 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051330 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rochlitz H. Department of Internal Medicine, University Hospital Bergmannsheil, University of Bochum, Bochum, Germany, DE aut NATIONALLICENCE 700 1- Voigt A. Department of Internal Medicine, University Hospital Bergmannsheil, University of Bochum, Bochum, Germany, DE aut NATIONALLICENCE 700 1- Lankat-Buttgereit B. Clinical Research Unit for Gastrointestinal Endocrinology, Department of Internal Medicine, Philipps-University of Marburg, Marburg, Germany, DE aut NATIONALLICENCE 700 1- Göke B. Clinical Research Unit for Gastrointestinal Endocrinology, Department of Internal Medicine, Philipps-University of Marburg, Marburg, Germany, DE aut NATIONALLICENCE 700 1- Heimberg H. Diabetes Research Centre, Vrije Universiteit Brussels, Brussels, Belgium, BE aut NATIONALLICENCE 700 1- Nauck M. A. Department of Internal Medicine, Knappschafts Hospital, University of Bochum, Bochum, Germany, DE aut NATIONALLICENCE 700 1- Schiemann U. Department of Internal Medicine B, University Hospital of Münster, Münster, Germany, DE aut NATIONALLICENCE 700 1- Schatz H. Department of Internal Medicine, University Hospital Bergmannsheil, University of Bochum, Bochum, Germany, DE aut NATIONALLICENCE 700 1- Pfeiffer A. F. H. Department of Internal Medicine, University Hospital Bergmannsheil, University of Bochum, Bochum, Germany, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer