title: Increased melatonin synthesis in pineal glands of rats in streptozotocin induced type 1 diabetes.
abstract: It is well-documented that melatonin influences insulin secretion. The effects are mediated by specific, high-affinity, pertussis-toxin-sensitive, G protein-coupled membrane receptors (MT(1) as well MT(2)), which are present in both the pancreatic tissue and islets of rats and humans, as well as in rat insulinoma cells (INS1). Via the Gi-protein-adenylatecyclase-3',5'-cyclic adenosine monophosphate (cAMP) and, possibly, the guanylatecyclase-cGMP pathways, melatonin decreases insulin secretion, whereas, by activating the Gq-protein-phospholipase C-IP(3) pathway, it has the opposite effect. For further analysis of the interactions between melatonin and insulin, diabetic rats were investigated with respect to melatonin synthesis in the pineal gland and plasma insulin levels. In this context, recent investigations have proven that type 2 diabetic rats and humans display decreased melatonin levels, whereas type 1 diabetic IDDM rats or those with diabetes induced by streptozotocin (STZ) of the present study show increased plasma melatonin levels and elevated AA-NAT-mRNA. Furthermore, the mRNA of pineal insulin receptors and beta1-adrenoceptors, including the clock genes Per1 and Bmal1 and the clock-controlled output gene Dbp, increases in both young and middle-aged STZ rats. The results therefore indicate that the decreased insulin levels in STZ-induced type 1 diabetes are associated with higher melatonin plasma levels. In good agreement with earlier investigations, it was shown that the elevated insulin levels observed in type 2 diabetes, are associated with decreased melatonin levels. The results thus prove that a melatonin-insulin antagonism exists. Astonishingly, notwithstanding the drastic metabolic disturbances in STZ-diabetic rats, the diurnal rhythms of the parameters investigated are maintained.
authors.affiliation: Institute of Anatomy and Cell Biology, Martin Luther University, Halle-Wittenberg, Halle, Germany. elmar.peschke@medizin.uni-halle.de
authors.forename: Elmar
authors.initials: E
authors.lastname: Peschke
authors.forename: Sabine
authors.initials: S
authors.lastname: Wolgast
authors.forename: Ivonne
authors.initials: I
authors.lastname: Bazwinsky
authors.forename: Klaus
authors.initials: K
authors.lastname: Pönicke
authors.forename: Eckhard
authors.initials: E
authors.lastname: Muhlbauer
mesh_terms: D056930:ARNTL Transcription Factors; D000121:Acetylserotonin O-Methyltransferase / Q000032:analysis / Q000235:genetics; D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000032:analysis / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics; D002940:Circadian Rhythm; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007328:Insulin / Q000097:blood*; D008297:Male; D008550:Melatonin / Q000096:biosynthesis* / Q000097:blood; D056950:Period Circadian Proteins; D010870:Pineal Gland / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044094:Receptors, Melatonin / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics
chemical_list: D056930:ARNTL Transcription Factors; D000121:Acetylserotonin O-Methyltransferase; D047068:Arylalkylamine N-Acetyltransferase; D051792:Basic Helix-Loop-Helix Proteins; D001786:Blood Glucose; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; D008550:Melatonin; D056950:Period Circadian Proteins; D044094:Receptors, Melatonin; D014157:Transcription Factors; C538960:BMAL1 protein, human; C485975:DBP protein, rat; C539022:PER1 protein, human; C539024:Per1 protein, rat; C520223:Aanat protein, rat