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

2019 ◽  
Vol 2 (3) ◽  
pp. 139-151
Author(s):  
Jose Sinesio-Jr ◽  
Paula Bargi-Souza ◽  
Raphael A Matos ◽  
Eduardo Almeida Leite ◽  
Daniella Carmo Buonfiglio ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Mrna Expression ◽  
Cardiac Dysfunction ◽  
Male Rats ◽  
Diabetic Rat ◽  
Dark Phase ◽  
Metabolic Dysfunction ◽  
Multiple Organs ◽  
Type 2 Diabetic

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.

scholarly journals Reverse Feeding Suppresses the Activity of the GH Axis in Rats and Induces a Preobesogenic State

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 869-882 ◽  
Author(s):  
Camilla A.-M. Glad ◽  
Edward E. J. Kitchen ◽  
Gemma C. Russ ◽  
Sophie M. Harris ◽  
Jeffrey S. Davies ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Phase Inversion ◽  
Fatty Acid Synthase ◽  
Uncoupling Protein ◽  
Expression Patterns ◽  
Pulse Height ◽  
Male Rats ◽  
Dark Phase ◽  
Peroxisome Proliferator ◽  
Gh Secretion

Reversed feeding (RF) is known to disrupt hormone rhythmicity and metabolism. Although these effects may be mediated in part by phase inversion of glucocorticoid secretion, the precise mechanism is incompletely characterized. In this study, we demonstrate that acute nocturnal food deprivation in male rats suppressed the amplitude of spontaneous GH secretion during the dark phase by 62% (P < 0.001), without affecting baseline secretion. Prolonged RF, which reduced pituitary weight (by 22%; P < 0.05), also suppressed GH pulse height sufficiently to reduce skeletal growth (by 4–5%; P < 0.01) and terminal liver weight (by 11%; P < 0.001). Despite this suppression of the GH axis, proportionate adiposity was not elevated, probably due to the accompanying 16% reduction in cumulative food intake (P < 0.01). We demonstrate that RF also resulted in phase inversion of core clock gene expression in liver, abdominal white adipose tissue (WAT) and skeletal muscle, without affecting their expression patterns in the suprachiasmatic nucleus. In addition, RF resulted in phase inversion of hepatic peroxisome proliferator-activated receptor γ2 mRNA expression, a 3- to 5-fold elevation in fatty acid synthase mRNA in WAT in both light- and dark-phase samples (P < 0.01) and an elevation in muscle uncoupling protein 3 mRNA expression at the beginning of the light phase (P < 0.01). Consumption of a high-fat diet increased inguinal (by 36%; P < 0.05) and retroperitoneal WAT weight (by 72%; P < 0.01) only in RF-maintained rats, doubling the efficiency of lipid accumulation (P < 0.05). Thus, RF not only desynchronizes central and peripheral circadian clocks, and suppresses nocturnal GH secretion, but induces a preobesogenic state.

scholarly journals An anxiolytic drug buspirone ameliorates hyperglycemia and endothelial dysfunction in type 2 diabetic rat model

2020 ◽  
Vol 45 (4) ◽  
pp. 397-404
Author(s):  
Tugba Gurpinar Çavuşoğlu ◽  
Ertan Darıverenli ◽  
Kamil Vural ◽  
Nuran Ekerbicer ◽  
Cevval Ulman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Insulin Levels ◽  
Type 2 Diabetic

AbstractObjectivesType 2 diabetes is a common metabolic disease and anxiety disorders are very common among diabetics. Buspirone is used in the treatment of anxiety, also having blood glucose-lowering effects. The aim of the study was to investigate the effects of buspirone on the glucose and lipid metabolism as well as vascular function in type 2 diabetic rats.MethodsA type 2-diabetic model was induced through a high-fat diet for eight weeks followed by the administration of low-dose streptozotocin (35 mg/kg, intraperitoneal) in rats. Buspirone was given at two different doses (1.5 mg/kg/d and 5 mg/kg/d) and combined with metformin (300 mg/kg/d). The fasting glucose and insulin levels, lipid profile were analyzed, and vascular response measured from the thoracic aorta was also evaluated.ResultsBoth doses of buspirone caused a significant improvement in fasting blood glucose levels. In particular, the buspirone treatment, combined with metformin, improved endothelial dysfunction and was found to be correlated with decreased nitrate/nitrite levels.ConclusionsBuspirone may be effective in the treatment of type 2 diabetes, either alone or in combination with other treatments, particularly in terms of endothelial dysfunction, inflammation and impaired blood glucose, and insulin levels.

scholarly journals COMP-Angiopoietin-1 Promotes Cavernous Angiogenesis in a Type 2 Diabetic Rat Model

2013 ◽  
Vol 28 (5) ◽  
pp. 725 ◽  
Author(s):  
Sun-Ouck Kim ◽  
Hyun-Suk Lee ◽  
Kyuyoun Ahn ◽  
Kwangsung Park
Keyword(s):  
Rat Model ◽  
Diabetic Rat ◽  
Diabetic Rat Model ◽  
Type 2 Diabetic ◽  
Angiopoietin 1

scholarly journals Daily Fasting Blood Glucose Rhythm in Male Mice: A Role of the Circadian Clock in the Liver

Endocrinology ◽  
2015 ◽  
Vol 157 (2) ◽  
pp. 463-469 ◽  
Author(s):  
Hitoshi Ando ◽  
Kentaro Ushijima ◽  
Shigeki Shimba ◽  
Akio Fujimura
Keyword(s):  
Blood Glucose ◽  
Circadian Clock ◽  
Mrna Expression ◽  
Hepatic Glucose Production ◽  
Critical Role ◽  
Fasting Blood Glucose ◽  
Glucose Production ◽  
Diabetic Patients ◽  
Dark Phase ◽  
Dawn Phenomenon

Abstract Fasting blood glucose (FBG) and hepatic glucose production are regulated according to a circadian rhythm. An early morning increase in FBG levels, which is pronounced among diabetic patients, is known as the dawn phenomenon. Although the intracellular circadian clock generates various molecular rhythms, whether the hepatic clock is involved in FBG rhythm remains unclear. To address this issue, we investigated the effects of phase shift and disruption of the hepatic clock on the FBG rhythm. In both C57BL/6J and diabetic ob/ob mice, FBG exhibited significant daily rhythms with a peak at the beginning of the dark phase. Light-phase restricted feeding altered the phase of FBG rhythm mildly in C57BL/6J mice and greatly in ob/ob mice, in concert with the phase shifts of mRNA expression rhythms of the clock and glucose production–related genes in the liver. Moreover, the rhythmicity of FBG and Glut2 expression was not detected in liver-specific Bmal1-deficient mice. Furthermore, treatment with octreotide suppressed the plasma growth hormone concentration but did not affect the hepatic mRNA expression of the clock genes or the rise in FBG during the latter half of the resting phase in C57BL/6J mice. These results suggest that the hepatic circadian clock plays a critical role in regulating the daily FBG rhythm, including the dawn phenomenon.

Visfatin, TNF-α and IL-6 mRNA Expression is Increased in Mononuclear Cells from Type 2 Diabetic Women

2007 ◽  
Vol 39 (10) ◽  
pp. 758-763 ◽  
Author(s):  
P. Tsiotra ◽  
C. Tsigos ◽  
E. Yfanti ◽  
E. Anastasiou ◽  
M. Vikentiou ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Mononuclear Cells ◽  
Tnf Α ◽  
Type 2 Diabetic
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