Pineal melatonin synthesis is decreased in type 2 diabetic Goto-Kakizaki rats.

Abstract

AIMS: It is not well understood why the amplitude of melatonin rhythms is reduced in diabetic animals and humans. This paper addresses the differences in the pineal melatonin synthesis of type 2 diabetic Goto-Kakizaki (GK) rats compared to non-diabetic Wistar rats (8 and 50 weeks old). MAIN METHODS: Plasma melatonin concentrations and the pineal content of melatonin and its precursors (tryptophan, 5-hydroxytryptophan, serotonin, and N-acetylserotonin) were quantified at the middle of the day and night. Additionally, the expression of melatonin synthesizing enzymes, pineal noradrenaline content, and pineal protein content were considered, and the melatonin secreting capacity of pineal glands was studied in vitro. KEY FINDINGS: The pineal glands of diabetic GK rats have a different expression pattern of melatonin synthesizing enzymes. The amount of all precursors of melatonin is reduced in pineal glands of diabetic GK rats. The pineal glands of diabetic GK rats contain less noradrenaline, indicating a reduced stimulation of nighttime melatonin synthesis. The pineal glands of diabetic GK rats produce less melatonin in reaction to noradrenaline in vivo and in vitro. The pineal glands of diabetic GK rats contain less protein, probably a consequence of diabetic neuropathy. SIGNIFICANCE: This is the first time that melatonin synthesis is examined in a type 2 diabetic rat model. The present data unveiled several reasons for a reduced melatonin secretion in diabetic animals and presents an important link in the interaction between melatonin and insulin.