Syntaxin4 interacting protein (Synip) binds phosphatidylinositol (3,4,5) triphosphate.

The insulin responsive Glut4 transport vesicles contain the v-SNARE protein Vamp2 that associate with the plasma membrane t-SNARE protein Syntaxin 4 to drive insulin-stimulated Glut4 translocation in skeletal muscle and adipocytes. The syntaxin 4 interacting protein (Synip) binds to syntaxin 4 in the basal state and dissociates in the insulin-stimulated state allowing for the subsequent binding of Vamp2 containing Glut4 vesicles and fusion with the plasma membrane. In this study, we have found that Synip binds phosphatidylinositol 3,4,5-triphosphate (PIP3), but not phosphatidylinositol 3 phosphate (PIP) or phosphatidylinositol 3,4-biphosphate (PIP2) through the Synip WW domain as deletion of this domain (Synip ΔWW) failed to bind PIP3.

Glucagon plays an important role in the modification of insulin secretion by leptin.

Obese people show marked hyerinsulinemia, but the exact mechanism has not been clarified. Hyperleptinemia is one of possible candidates, although there is an obvious difference in the effect of leptin on insulin secretion between isolated pancreatic islets and β-cell line. Since glucagon may modulate the effect of leptin on insulin secretion, we determined the influences of glucagon in the leptin effect on insulin secretion.

Leptin activates a novel CNS mechanism for insulin-independent normalization of severe diabetic hyperglycemia.

The brain has emerged as a target for the insulin-sensitizing effects of several hormonal and nutrient-related signals. The current studies were undertaken to investigate mechanisms whereby leptin lowers circulating blood glucose levels independently of insulin. After extending previous evidence that leptin infusion directly into the lateral cerebral ventricle ameliorates hyperglycemia in rats with streptozotocin-induced uncontrolled diabetes mellitus, we showed that the underlying mechanism is independent of changes of food intake, urinary glucose excretion, or recovery of pancreatic β-cells.

Fasting concentrations of nesfatin-1 are negatively correlated with body mass index in non-obese males.

Background: We recently identified a novel anorexigenic protein, nesfatin-1, which is processed from nesfatin/nucleobindin-2 (NUCB2). However, the clinical importance of this protein has not been determined.

Objective: To investigate its clinical significance in humans, we have established a new specific enzyme-linked immunosorbent assay (ELISA) for human nesfatin-1 in peripheral blood and measured its circulating concentration in healthy subjects.

Leptin deficiency causes insulin resistance induced by uncontrolled diabetes.

Objective: Depletion of body fat stores during uncontrolled, insulin-deficient diabetes (uDM) results in markedly reduced plasma leptin levels. This study investigated the role of leptin deficiency in the genesis of severe insulin resistance and related metabolic and neuroendocrine derangements induced by uDM.

Research Design And Methods: Adult male Wistar rats remained nondiabetic or were injected with the beta-cell toxin, streptozotocin (STZ) to induce uDM and subsequently underwent subcutaneous implantation of an osmotic minipump containing either vehicle or leptin at a dose (150 microg/kg/day) designed to replace leptin at nondiabetic plasma levels.

Central administration of interleukin-4 exacerbates hypothalamic inflammation and weight gain during high-fat feeding.

In peripheral tissues, the link between obesity and insulin resistance involves low-grade inflammation induced by macrophage activation and proinflammatory cytokine signaling. Since proinflammatory cytokines are also induced in the hypothalamus of animals placed on a high-fat (HF) diet and can inhibit neuronal signal transduction pathways required for normal energy homeostasis, hypothalamic inflammation is hypothesized to contribute to the pathogenesis of diet-induced obesity (DIO). We addressed this hypothesis by perturbing the inflammatory milieu of the hypothalamus in adult male Wistar rats using intracerebroventricular (icv) administration of interleukin-4 (IL-4), a Th2 cytokine that promotes alternative activation (M2) of macrophages and microglia.

Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway.

The hypothalamic paraventricular nucleus (PVN) functions as a center to integrate various neuronal activities for regulating feeding behavior. Nesfatin-1, a recently discovered anorectic molecule, is localized in the PVN. However, the anorectic neural pathway of nesfatin-1 remains unknown.

Serious complications after a proximal gastrectomy with a jejunal pouch interposition for gastric cancer.

Proximal gastrectomy with jejunal interposition is a common surgical method in Japan, because the procedure has been shown to give a better post-operative quality of life. Some complications are associated with it. However, esophageal candidiasis and linear marginal ulcer along the gastrojejunal anastomosis after the surgical method has never previously been reported.

Prolonged intrahepatic cholestasis after exposure to loxoprofen.

Objective: The objective of this report was to describe a case of prolonged intrahepatic cholestasis likely associated with the use of loxoprofen, a phenylpropionate NSAID.

Methods: A 36-year-old female patient was transferred to Gunma University Hospital, Maebashi, Japan, with progressive pruritus and jaundice that developed after 5-day treatment with 120 mg/d of loxoprofen (maximum recommended dose, 180 mg/d) for menstrual pain. Liver function tests found the following concentrations: total bilirubin, 27.

Incidence of β3-adrenergic receptor polymorphism and prediction of successful weight reduction with mazindol therapy in severely obese Japanese subjects.

Mazindol, a centrally acting monoamine re-uptake inhibitor, enhances satiety and supports body weight loss, but response to this drug among obese patients is very variable. The possible involvement of the Trp64Arg polymorphism of the β3-adrenergic receptor (ADRB3) gene in the development of severe obesity and weight loss response to anorexigenic drugs has not been established. In the present study, the allelic frequency of the Trp64Arg ADRB3 gene polymorphism was determined in massively obese Japanese outpatients (BMI > 35 kg/m(2)), and we investigated whether allelic differences may determine the weight loss effect of mazindol.

Identification of nesfatin-1 as a satiety molecule in the hypothalamus.

The brain hypothalamus contains certain secreted molecules that are important in regulating feeding behaviour. Here we show that nesfatin, corresponding to NEFA/nucleobindin2 (NUCB2), a secreted protein of unknown function, is expressed in the appetite-control hypothalamic nuclei in rats. Intracerebroventricular (i.

Molecular mechanisms associated with leptin resistance: n-3 polyunsaturated fatty acids induce alterations in the tight junction of the brain.

High-fat diets cause peripheral leptin resistance, and dietary lipid composition affects sensitivity to leptin. We examined the role of n-3 polyunsaturated fatty acid (PUFA) in peripheral leptin resistance. Dietary PUFAs (0.

Relationship between hyperinsulinemia and pulse wave velocity in moderately hyperglycemic patients.

Aim: Arterial stiffness assessed by pulse wave velocity (PWV) reflects early stage arteriosclerosis. The influence of hyperinsulinemia on peripheral vascular disease (PVD) is still unknown. We determined the influences of hyperinsulinemia on PVD assessed by PWV in moderately hyperglycemic patients.