Hypothalamic insulin expression increases after the short-term fasting

Abstract

Introduction: Among other processes, insulin in the brain regulates glucose metabolism, appetite and neuronal growth. Here we examined effect of six-hour fasting on insulin expression in rat hypothalamus and its possible involvement in the hypothalamic glucose transport. Methods: Insulin mRNA expression was assessed by PCR. Content of insulin, phosphorylated insulin receptor (pIR) and glucose transporters (GLUT1, 2, 3) was detected by immunoblotting. Anatomical and cellular localization of insulin immunopositivity was analyzed by immunofluorescence. Serum and cerebrospinal fluid glucose levels were measured with an Exac-tech glucose analyzer. Results: Short-term fasting increased both insulin II mRNA expression and insulin content in the hypothalamus. Increased insulin immunopositivity was observed in the periventricular NeuN-positive cells and in the ependymal cells surrounding the third ventricle. The amounts of pIR, GLUT1 and GLUT3 were increased, whereas GLUT2 remained unchanged. Unlike blood glucose which was lowered, cerebrospinal fluid glucose was not affected by six-hour fasting. Conclusion: Our results showed that de novo insulin production occurred in the hypothalamus during the short-term fasting. The fact that hypothalamic GLUT expression was either increased or unchanged suggests that centrally produced insulin may be involved in the regulation of glucose transport in the state of acutely disturbed energy homeostasis.