title: Catecholamines are the key for explaining the biological relevance of insulin-melatonin antagonisms in type 1 and type 2 diabetes.
abstract: In this paper, we analyze the biological relevance of melatonin in diabetogenesis. As has recently been demonstrated, melatonin decreases insulin secretion via specific melatonin receptor isoforms (MT1 and MT2) in the pancreatic β-cells. In addition, type 2 diabetic rats, as well as patients, exhibit decreased melatonin levels, whereas the levels in type 1 diabetic rats are increased. The latter effects were normalized by insulin substitution, which signifies that a specific receptor-mediated insulin-melatonin antagonism exists. These results are in agreement with several recent genome-wide association studies, which have identified a number of single nucleotide polymorphisms in the MTNR1B gene, encoding the MT2 receptor, that were closely associated with a higher prognostic risk of developing type 2 diabetes. We hypothesize that catecholamines, which decrease insulin levels and stimulate melatonin synthesis, control insulin-melatonin interactions. The present results support this assertion as we show that catecholamines are increased in type 1 but are diminished in type 2 diabetes. Another important line of inquiry involves the fact that melatonin protects the β-cells against functional overcharge and, consequently, hinders the development of type 2 diabetes. In this context, it is striking that at advanced ages, melatonin levels are reduced and the incidence of type 2 diabetes is increased. Thus, melatonin appears to have a protective biological role. Here, we strongly repudiate misconceptions, resulting from observations that melatonin reduces the plasma insulin level, that the blockage of melatonin receptors would be of benefit in the treatment of type 2 diabetes.
authors.affiliation: Institute of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany. elmar.peschke@medizin.uni-halle.de
authors.forename: E
authors.initials: E
authors.lastname: Peschke
authors.forename: K
authors.initials: K
authors.lastname: Hofmann
authors.forename: K
authors.initials: K
authors.lastname: Pönicke
authors.forename: D
authors.initials: D
authors.lastname: Wedekind
authors.forename: E
authors.initials: E
authors.lastname: Mühlbauer
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004837:Epinephrine / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007329:Insulin Antagonists / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000097:blood / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D010870:Pineal Gland / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007329:Insulin Antagonists; D011972:Receptor, Insulin; D008550:Melatonin; D009638:Norepinephrine; D004837:Epinephrine