Endocrine Abstracts

There is a well documented link between melatonin and insulin. Morphological, molecular and functional investigations have shown that the pineal hormone melatonin (MT) influences the insulin secretion. The effects were mediated by specific, high-affinity, pertussis-toxin-sensitive, G-protein-coupled MT1- as well as MT2-membrane receptors which were detected in pancreatic tissue and islets of rats and humans and additionally in rat insulinoma cells INS1. Using the Gi-protein-adenylylcyclase-cAMP- and possibly the cGMP-pathway, MT decreases the insulin secretion, whereas using the Gq-phospholipase C-IP3-pathway MT increases the insulin secretion.

For further analysis of MT-insulin-interactions, plasma MT levels were measured in diabetic rats and humans. In this context, own recent investigations have proven that type 2-diabetic rats and humans displayed a decreased MT level whereas type 1-diabetic rats (induced by streptozotocin, STZ) showed an increased plasma MT level. In addition, the rate-limiting enzyme of the MT synthesis, the arylalkylamine-N-acetyltransferase (AANAT), was investigated by quantitative RT-PCR analysis. Furthermore, plasma catecholamines by HPLC technique, pineal insulin-receptor and adrenoceptor status in addition to clock gene transcripts (Per1 and Bmal1) and the clock output gene dbp were analyzed in a circadian series by RT-PCR. In conclusion, the results emphasize that increased insulin levels, which were observed in some forms of type 2-diabetes, are combined with a decreased MT level. On the other hand, decreased insulin levels of STZ-induced type 1-diabetes are combined with a higher MT plasma level. Astonishingly, the drastic metabolic disturbances of diurnal rhythmicities of the parameters investigated were maintained. The conserved melatonin rhythm combined with an unchanged day-night-rhythmicity of AANAT reflect that the master clock, the hypothalamic nucleus suprachiasmaticus, was not affected.