Melatonin and the heart circadian clock of euglycemic and type 2 diabetic male rats: a transcriptional evaluation

Abstract

Diabetes increases risk of various comorbidities, including retinopathy, neuropathy, and cardiovascular disease, comprising both ischemic and non-ischemic cardiomyopathy. Cardiac dysfunction during diabetes is associated with perturbations at histologic, metabolic, biochemical and molecular levels. The circadian clock is misaligned in multiple organs during diabetes, including the heart. Such alterations in clock function have been postulated to play a causal role in cardiac dysfunction even though the mechanisms leading to circadian misalignment are currently unknown. Melatonin has been reported to alter heart circadian clock components and its circulating levels are decreased during diabetes. These observations led to the hypothesis that decreased melatonin levels during diabetes could be related to mismanagement of the heart clock. To evaluate this hypothesis, in the current study male Wistar and non-obese type 2 diabetic Goto-Kakizaki (GK) rats were given melatonin supplementation in their drinking water during the dark phase (for 12-wks), followed by assessment of clock component and the mRNA expression of the clock-controlled genes in the hearts of these animals. Melatonin supplementation significantly altered mRNA expression of targeted genes in both euglycemic and diabetic rat hearts. Collectively, under the condition of diabetes, the jeopardized pineal melatonin synthesis with misalignment of cardiac circadian clock components may likely mediate heart metabolic dysfunction, and/or even cause cardiovascular diseases.