Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: a route for ameliorating hyperphagia and obesity.

Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt suppresses feeding and, when infused subchronically, ameliorates hyperphagic obesity. However, the route through which peripheral Oxt informs the brain is obscure.

Glucagon directly interacts with vagal afferent nodose ganglion neurons to induce Ca(2+) signaling via glucagon receptors.

Glucagon is released from the pancreatic islets postprandially and under hypoglycemic and cold conditions, and regulates glucose metabolism, feeding, energy expenditure and heat production, the functions partly controlled by the brain. Peripheral glucagon could signal to the brain via passing through the blood-brain barrier and/or acting on the vagal afferent. However, the latter remains to be determined.

Effects of inorganic mercury and methylmercury on osteoclasts and osteoblasts in the scales of the marine teleost as a model system of bone.

To evaluate the effects of inorganic mercury (InHg) and methylmercury (MeHg) on bone metabolism in a marine teleost, the activity of tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) as indicators of such activity in osteoclasts and osteoblasts, respectively, were examined in scales of nibbler fish (Girella punctata). We found several lines of scales with nearly the same TRAP and ALP activity levels. Using these scales, we evaluated the influence of InHg and MeHg.

Insulin Activates Vagal Afferent Neurons Including those Innervating Pancreas via Insulin Cascade and Ca(2+) Influx: Its Dysfunction in IRS2-KO Mice with Hyperphagic Obesity.

Some of insulin's functions, including glucose/lipid metabolism, satiety and neuroprotection, involve the alteration of brain activities. Insulin could signal to the brain via penetrating through the blood-brain barrier and acting on the vagal afferents, while the latter remains unproved. This study aimed to clarify whether insulin directly regulates the nodose ganglion neurons (NGNs) of vagal afferents in mice.

Intraportal GLP-1 stimulates insulin secretion predominantly through the hepatoportal-pancreatic vagal reflex pathways.

We previously reported that glucagon-like peptide-1 (GLP-1) appearance in the portal vein facilitates hepatic vagal afferent activity, and this further augments reflexively the pancreatic vagal efferents in anesthetized rats, suggesting a neuroincretin effect of GLP-1. To determine whether the GLP-1-induced vagal pathways lead to a neuronal-mediated component (NMC) of insulin secretion, we infused GLP-1 at a physiological or pharmacological dose (1 or 3 pmol·kg(-1)·min(-1), respectively) into the portal vein in conscious rats with selective hepatic vagotomy (Vagox) or sham operation (Sham). The experiments consisted of two sequential 10-min intraportal infusions (P1 and P2): glucose at a physiological rate (56 μmol·kg(-1)·min(-1)) in P1 and the glucose plus GLP-1 or vehicle in P2.

Histidine augments the suppression of hepatic glucose production by central insulin action.

Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation.

Pancreatic polypeptide and peptide YY3-36 induce Ca2+ signaling in nodose ganglion neurons.

Peripheral injection of pancreatic polypeptide (PP) and peptide YY(3-36) (PYY(3-36)), the hormones released in response to meals, reduce food intake, in which the rank order of the potency is PP>PYY(3-36). These anorectic effects are abolished in abdominal vagotomized rats, suggesting that PP and PYY(3-36) induce anorexia via vagal afferent nerves. However, it is not clear whether PP and PYY(3-36) directly act on vagal afferent neurons.

Genetic suppression of ghrelin receptors activates brown adipocyte function and decreases fat storage in rats.

To clarify the role of ghrelin and its receptor (GHS-R) in the regulatory mechanism of energy metabolism, we analyzed transgenic (Tg) rats expressing an antisense GHS-R mRNA under the control of the tyrosine hydroxylase (TH) promoter. Tg rats showed lower visceral fat weight and higher O(2) consumption, CO(2) production, rectal temperature, dark-period locomotor activity, brown adipose tissue (BAT) weight and uncoupling protein 1 expression compared with wild-type (WT) rats on a standard diet. A high-fat diet for 14days significantly increased body weight, visceral fat weight, and the sizes of white and brown adipocytes in WT rats but not in Tg rats compared with the corresponding standard-diet groups.

Nesfatin-1 evokes Ca2+ signaling in isolated vagal afferent neurons via Ca2+ influx through N-type channels.

Nesfatin-1, processed from nucleobindin 2, is an anorexigenic peptide expressed in the brain and several peripheral tissues including the stomach and pancreas. Peripheral, as well as intracerebroventricular, administration of nesfatin-1 suppresses feeding behavior, though underlying mechanisms are unknown. In this study, we examined effects of nesfatin-1 on cytosolic Ca(2+) concentration ([Ca(2+)](i)) in the neurons isolated from the vagal afferent nodose ganglion of mice.

Insulin responses to selective arterial calcium infusion under hyperinsulinemic euglycemic glucose clamps: case studies in adult nesidioblastosis and childhood insulinoma.

Selective arterial calcium stimulation and hepatic venous sampling (ASVS) for insulin secretion is used as a diagnostic procedure in patients with insulinomas or adult nesidioblastosis. In some of those patients, severe hypoglycemia requiring urgent glucose administration occurs during the procedure. Such glucose administration, however, may affect the results and damage the validity of the test.

Receptor gene expression of glucagon-like peptide-1, but not glucose-dependent insulinotropic polypeptide, in rat nodose ganglion cells.

We previously reported that afferent signals of the rat hepatic vagus increased upon intraportal appearance of insulinotropic hormone glucagon-like peptide-1(7-36) amide (GLP-1), but not glucose-dependent insulinotropic polypeptide (GIP). To obtain molecular evidence for the vagal chemoreception of GLP-1, the concept derived from those electrophysiological observations, receptor gene expressions of GLP-1 and GIP in the rat nodose ganglion were examined by means of reverse transcriptase-mediated polymerase chain reaction (RT-PCR) and Northern blot analysis. Gene expression of the GLP-1 receptor was clearly detected by both RT-PCR and Northern blot analysis.

Glucagon-like peptide-1 evokes action potentials and increases cytosolic Ca2+ in rat nodose ganglion neurons.

We previously reported that the intraportal appearance of glucagon-like peptide-1 (GLP-1) facilitates the afferent activity (the spike discharge firing rate) of the rat hepatic vagus in a dose-dependent fashion. To examine whether GLP-1 directly activates single neurons isolated from the rat nodose ganglion, GLP-1-induced changes of the membrane potential and cytosolic-free Ca2+ concentration ([Ca2+]i) in the cells were measured using whole-cell patch-clamp and microfluorometric techniques, respectively. GLP-1 application (3 x 10(-12) - 3 x 10(-9) M) induced a gradual depolarization from a mean resting membrane potential of - 55.