Cardiomyocytes circadian clock in adaptation of the heart to STZ-induced diabetes mellitus

• Grant number: 12/02443-4
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: May 01, 2012
• End date: April 30, 2013
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Carla Roberta de Oliveira Carvalho
• Grantee: Rodrigo Antonio Pelliciari Garcia
• Supervisor: Martin E. Young
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Alabama at Birmingham (UAB), United States
• Associated to the scholarship: 07/07790-6 - Role of insulin on the regulation of melatonin synthesis by pineal gland: action mechanisms and functional characteristics, BP.PD

Abstract

Our research group has being studying the modulation events of melatonin synthesis by peptidergic systems as insulin and leptin, as well as the actions of melatonin as a zeitgeber (time-keeper) to the heart. We have shown that insulin potentiates melatonin synthesis in the pineal gland due to an increase in the activities of the main enzymes involved on the synthesis of the pineal hormone and this potentiation is mediated via PI3K. Actually, we are investigating the action of leptin on melatonin synthesis, once it seems to exist a relationship of insulin modulatory effect with the two periods of insulin sensitivity within pineal gland, which are coincident with the two moments of bouts of feeding of the rats, where glicemia is increased. In fact, in culture pineal gland leptin seems to inhibit melatonin synthesis. In addition diabetic strptozotocin-induced animals presents a clear reduction of melatonin synthesis in pineal gland and retina and the insulin administration reestablish melatonin synthesis to control values. Thus, due to a diabetic condition, where there is no insulin potentiation effect, also with a reduction of melatonin synthesis and leptin levels we believe that the heart which is an important target for melatonin and also for the diabetic condition, could have the cardiomyocytes circadian clock expression altered, which possesses an important function within the heart not only altering gene expression and metabolism but also contractile function. Therefore, the main aim of this study is to define the role of cardiomyocytes circadian clock in adaptation of the heart to STZ-induced diabetes mellitus in two animal models (both specific to cardiomyocytes): a Clock dominant negative (CCM) and a Bmal1 knockout (CBK). For the transcriptional analysis of the adaptation of the cardiomyocytes clock to the diabetes RNA-seq (transcriptome) will be performed using next generation sequencing. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PELICIARI-GARCIA, RODRIGO A.; GOEL, MEHAK; ARISTORENAS, JONATHAN A.; SHAH, KRISHNA; HE, LAN; YANG, QINGLIN; SHALEV, ANATH; BAILEY, SHANNON M.; PRABHU, SUMANTH D.; CHATHAM, JOHN C.; et al. Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1861, n. 10, SI, p. 1579-1595, OCT 2016. (12/02443-4)

PELICIARI-GARCIA, RODRIGO A.; GOEL, MEHAK; ARISTORENAS, JONATHAN A.; SHAH, KRISHNA; HE, LAN; YANG, QINGLIN; SHALEV, ANATH; BAILEY, SHANNON M.; PRABHU, SUMANTH D.; CHATHAM, JOHN C.; et al. Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1861, n. 10, p. 17-pg., 2016-10-01. (12/02443-4)