Leptin inhibits and ghrelin augments hypothalamic noradrenaline release after stress.

Metabolic conditions affect hypothalamo-pituitary-adrenal responses to stressful stimuli. Here we examined effects of food deprivation, leptin and ghrelin upon noradrenaline release in the hypothalamic paraventricular nucleus (PVN) and plasma adrenocorticotropic hormone (ACTH) concentrations after stressful stimuli. Food deprivation augmented both noradrenaline release in the PVN and the increase in plasma ACTH concentration following electrical footshocks (FSs). An intracerebroventricular injection of leptin attenuated the increases in hypothalamic noradrenaline release and plasma ACTH concentrations after FSs, while ghrelin augmented these responses. These data suggest that leptin inhibits and ghrelin facilitates neuroendocrine stress responses via noradrenaline release and indicate that a decrease in leptin and an increase in ghrelin release after food deprivation might contribute to augmentation of stress-induced ACTH release in a fasting state.

Diabetic lipemia with eruptive xanthomatosis in a lean young female with apolipoprotein E4/4.

Eruptive xanthomas in adults are usually indicative of chylomicronemia. Although diabetes mellitus is the most common secondary cause of chylomicronemia, which is designated as diabetic lipemia, the clinical characteristics of diabetes with regard to development of xanthomas are not well defined. In this paper, we describe a young female who displayed eruptive xanthomas as an initial manifestation of diabetic lipemia. The patient was a 20-year-old female with a body mass index of 18.9 kg/m2 and Marfanoid appearance. Her past history was unremarkable, except for patent ductus arteriosus and mild mental retardation. She was admitted to our division for eruptive xanthomas on the extremities and marked hyperglycemia (random glucose, 520 mg/dl) and hypertriglyceridemia (6880 mg/dl). She was diagnosed with Type 2 diabetes based on the positive family history of diabetes, residual secretory capacity of insulin, and absence of autoantibodies related to Type 1 diabetes. Based on the increase in the concentrations of both chylomicrons and very low density lipoproteins, type V hyperlipoproteinemia was diagnosed. After the initiation of insulin therapy, both hypertriglyceridemia and eruptive xanthomas subsided, without administering any hypolipidemic agents. Minimal model analysis of a frequently sampled intravenous glucose tolerance test revealed severe insulin resistance, despite the absence of obesity. Post-heparin lipoprotein lipase (LPL) activity was moderately decreased, and common mutations in the LPL gene were not demonstrated by genetic screening. The apolipoprotein E phenotype was E4/4, which is known to be associated with type V hyperlipoproteinemia. Hypoadiponectinemia of 1.7 microg/ml was also revealed, which may, in part, account for the insulin resistance and decreased LPL activity. In conclusion, the clustering of apolipoprotein E4/4 and hypoadiponectinemia, in addition to insulin resistance and poor glycemic control, might have resulted in hypertriglyceridemia with eruptive xanthomatosis in this subject.

Neuromedin U facilitates oxytocin release from the pituitary via beta adrenoceptors.

Neuromedin U activates noradrenergic neurones in the medulla oblongata and oxytocin neurones in the hypothalamus. Here we examined roles of noradrenergic transmission in oxytocin release from the pituitary after intracerebroventricular administration of neuromedin U in rats. Neuromedin U administration facilitated noradrenaline release in the supraoptic nucleus. Administration of a beta1 adrenoceptor antagonist, metoprolol, or a beta2 antagonist, ICI 118551 but not an alpha1 antagonist, benoxathian, reduced increases in plasma oxytocin concentrations observed after administration of neuromedin U, but plasma ACTH concentrations were not significantly changed. All theses data suggest that neuromedin U stimulates oxytocin release from the pituitary, at least in part, via activation of beta adrenoceptors.