Melatonin and type 2 diabetes - a possible link?
The aim of the present study was to determine the existence of melatonin membrane receptors and to examine the mRNA expression of nuclear orphan receptors in human pancreatic tissue, in an effort to explain differences between type 2 diabetic and metabolically healthy patients. Molecular and immunocytochemical investigations established the presence of the melatonin membrane receptors MT1 and MT2 in human pancreatic tissue and, notably, also in the islets of Langerhans. Results of a calculation model to determine mRNA expression ratios, as well as subjective analysis of immunoreactions, showed elevated MT1 receptor expression in comparison with MT2 expression. mRNA transcript levels of melatonin receptors appeared to be significantly higher in type 2 diabetic patients than in a control group. An upregulation of receptor expression in type 2 diabetic patients was also observed in immunocytochemical investigations. In addition, transcripts of the nuclear orphan receptors RORalpha, RZRbeta, RORgamma and RevErbalpha were detected in human pancreatic tissue and islets. In correlation with membrane melatonin receptors, data indicate increased mRNA expression levels of RORalpha, RZRbeta, and RORgamma in type 2 diabetic patients. Thus, our data demonstrate the existence of the melatonin membrane receptors MT1 and MT2 as well as mRNA expression of nuclear orphan receptors in human pancreatic tissue, with upregulated expression levels in type 2 diabetic patients.
Peschke
Elmar
E
Institute of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Halle, Germany. elmar.peschke@medizin.uni-halle.de
Stumpf
Ina
I
Bazwinsky
Ivonne
I
Litvak
Liudmila
L
Dralle
Henning
H
Mühlbauer
Eckhard
E
D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D008875:Middle Aged; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010179:Pancreas / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044122:Receptor, Melatonin, MT1 / Q000235:genetics / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D004268:DNA-Binding Proteins; C064353:NR1D1 protein, human; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; C539738:RORA protein, human; C539900:RORC protein, human; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D015534:Trans-Activators; D008550:Melatonin