Participation of clock genes in the modulation of insulin secretion in pancreatic islets of malnourished mice

Abstract

Basic physiological functions such as sleep-wake cycles, heart beats, body temperature, gastrointestinal motility and the whole endocrine metabolism oscillate along the day under control of a set of genes known as clock genes. These genes are expressed in hypothalamic neurons in the suprachiasmatic nucleus (SCN), the master clock, and also in peripheral tissues such as liver, heart and pancreas. Mice carrying mutations on the clock genes are susceptible to obesity, hyperglicemia, hypoinsulinemia, fatty liver and dyslipidemia. Over the years our research group has been describing pancreatic function in malnourished rodents. They show lower insulin secretion stimulated by glucose and other agents and increased tolerance to glucose and insulin. However, circadian oscillations of theses parameters were never assessed in this model. Liver from malnourished mice lose its circadian oscillation pattern and it correlates with increased susceptibility to become obese. These findings give support to epidemiological studies that found positive correlation between malnutrition during gestation and/or weaning and chronic diseases such as cancer, hypertension and type 2 diabetes in the adulthood. Here we postulate that the expression and oscillatory pattern of clock genes are altered in pancreatic islets and peripheral tissues of malnourished mice and are correlated with the insulin release and glucose tolerance described in this model.