We have identified an unusual potential dual Akt/protein kinase B consensus phosphorylation motif in the protein Synip (RxKxRS(97)xS(99)). Surprisingly, serine 97 is not appreciably phosphorylated, whereas 99 only a specific substrate for Akt2 but Akt1 or Akt3. Although wild-type (WT-Synip) undergoes insulin-stimulated dissociation from Syntaxin4, to phenylalanine mutant (S99F-Synip) resistant and fails display Syntaxin4 dissociation. Furthermore, overexpression of WT-Synip 3T3L1 adipocytes...

Abstract Tirzepatide, a dual glucagon-like peptide-1 receptor and gastric inhibitory peptide agonist, is an effective treatment for type 2 diabetes mellitus obesity, resulting in significant improvements glycated hemoglobin levels weight reduction. However, gastrointestinal side effects, including delayed emptying, have been reported. Recently, case of inadequate visualization during esophagogastroduodenoscopy due to substantial food residues patients treated with tirzepatide has This study...

To determine the downstream signaling pathways regulated by betacellulin (BTC) in comparison with epidermal growth factor (EGF), we used Chinese hamster ovary cells overexpressing human EGF receptor (ErbB1/EGFR). The overall time-dependent activation of EGFR autophosphorylation was identical treated 1 nm BTC or 1.5 EGF. Analysis site-specific phosphorylation demonstrated that and tyrosine Y1086 not significantly different. In contrast, Y1173 markedly reduced BTC-stimulated cells, compared...

Glucose transport and insulin resistance in the skeletal muscle of genetically obese (ob/ob) mouse has been studied animals at 6-7 wk age using an situ perfused hindquarter preparation. Rates glucose uptake radioactively labeled 2-deoxy-D-glucose were lower muscles from intact ob/ob mice than those their lean littermates. Following adrenalectomy basal rate or was restored to normal. The 2-deoxyglucose tested two concentrations. In mice, had no effect on uptake. Adrenalectomy, however,...

Insulin stimulation results in the activation of cyclin-dependent kinase-5 (CDK5) lipid raft domains via a Fyn-dependent phosphorylation on tyrosine residue 15. In turn, activated CDK5 phosphorylates Rho family GTP-binding protein TC10α threonine 197 that is sensitive to inhibitor olomoucine and blocked by small interfering RNA-mediated knockdown CDK5. The deficient mutant T197A-TC10α was not phosphorylated excluded from domain, whereas mimetic (T197D-TC10α) localized. resulted GTP loading...

Diabet. Med. 27, 1430–1435 (2010) Abstract Aims The study aimed to investigate early‐stage atherosclerosis in patients with impaired fasting glucose compared tolerance. Methods Body mass index, systolic blood pressure, plasma glucose, lipid variables, ankle–brachial pressure index and brachial–ankle pulse wave velocity were measured 2842 subjects from Takasaki city located approximately 100 km north of Tokyo Japan. divided into the following five groups based on a 75‐g oral tolerance test:...

Semaglutide is a well-designed drug with special coating that allows for oral administration to patients type 2 diabetes mellitus. However, taking semaglutide complain of its bitter taste. We therefore considered suggesting take hot water. When the water temperature was increased above 46.0°C but below 52.0°C, no taste perceived, daily mean interstitial glucose level remaining at target range. Taking helps reduce

Objective: The aim of this clinical study was to discover a new factor affecting muscle strength and quality in patients with type 2 diabetes (T2D). Materials methods: relationship between low-density lipoprotein cholesterol (LDL-C), random triglyceride (TG), high-density (HGL-C) levels were studied. Relative handgrip (RHGS) used evaluate muscular quality. RHGS calculated by dividing the absolute body mass index (BMI). Using stepwise method, multiple regression analysis conducted linear...

An immunofluorescence study using unfixed cryostat sections of rat pituitary glands was carried out on sera from 34 patients with Hashimoto's thyroiditis, 28 Graves' disease, 10 thyroid adenoma and 50 healthy subjects. After absorption liver tissues, 19 retained reactivity to anterior cell antibodies (PCA, 55.8%). On the other hand, in cells faint detected only 2 disease (7.1%) after their aceton powder. A similar result also obtained when PCA were compared thyroiditis high titers microsomal...

The mechanism of TNF-α-induced insulin resistance has remained unresolved with evidence for down-regulation effector targets effects or blockade proximal as well distal signaling events depending upon the dose, time, and cell type examined. To address this issue we examined acute actions TNF-α in differentiated 3T3L1 adipocytes. Acute (5-15 min) treatment 20 ng/ml (~0.8 nm) had no significant effect on IRS1-associated phosphatidylinositol 3-kinase. In contrast, increased insulin-stimulated...

Nucleobindin-2 is a 420-amino-acid EF-hand calcium-binding protein that undergoes proteolytic processing to generate an 82-amino-acid amino-terminal peptide termed nesfatin-1. To determine whether nucleobindin-2 has any biological function, was either overexpressed or knocked down by short hairpin RNA in cultured CHO cells expressing the human insulin and epidermal growth factor (EGF) receptors (CHO/IE) 3T3-L1 cells. Reduction expression inhibited EGF-stimulated MAPK kinase (S217/S221) Erk...

Although syntaxin 1 is generally thought to function as the primary target-N-ethylmaleimide-sensitive factor attachment protein receptor required for pancreatic β cell insulin secretion, we have observed that overexpression of a dominant-interfering 4 mutant (syntaxin 4/ΔTM) attenuated glucose-stimulated secretion in βHC-9 cells. Furthermore, these cells express selective 4-binding Synip interacting protein), and was specifically co-immunoprecipitated with but not 1. Overexpression...

Platelet-derived growth factor (PDGF) stimulation of skeletal muscle, cultured myotubes, and 3T3L1 adipocytes results in glucose transporter 4 (Glut4) translocation, albeit to a reduced level compared with insulin. To address the mechanism PDGF action, we have determined that Syntaxin negative regulatory protein, Munc18c, undergoes PDGF-stimulated phosphorylation on tyrosine residue 521. The Munc18c Y521 occurred concomitant dissociation protein from time frame consistent Glut4...

Nucleobindin-2 is a 420 amino acid EF-hand Ca²⁺ binding protein that can be further processed to generate an 82 terminal peptide termed Nesfatin-1. To examine the function of secreted in adipocyte differentiation, cultured 3T3-L1 cells were incubated with either 0 or 100 nM GST, GST-Nucleobindin-2, prior and during initiation differentiation. treatment decreased neutral lipid accumulation (Oil-Red O staining) expression several marker genes for differentiation (PPARγ, aP2, adipsin). When...

The fractional concentration of nitric oxide in exhaled air (FENO) is used as a biomarker eosinophilic airway inflammation. FENO increased patients with asthma. relationship between subjective asthma symptoms and inflammation an important issue. We expected that the women might be different from those men. Therefore, we investigated gender differences survey prevalence university students.The information about was obtained answers to European Community Respiratory Health Survey (ECRHS)...

It has been suggested that 5-hydroxytryptamine3 (5-HT3) receptors are involved in the control of phase III contractions stomach. We examined effect depletion endogenous 5-HT by p-chlorophenylalanine (pCPA) on spontaneously and motilin-induced conscious dogs, 5,6-dihydroxytryptamine (5,6-DHT) an isolated perfused dog Three-day treatment with pCPA significantly reduced plasma concentration content stomach, strongly suppressed spontaneous When recovered stomach after a 3-day treatment,...

The stability of the perfused mouse hindquarter was assessed for a period 5 h, and preparation shown to remain stable metabolic studies over this time period. Muscle protein synthesis degradation rates in lean diabetic-obese (db/db) mice were measured using situ preparation. 48% lower muscles intact db/db than controls when expressed per gram TCA precipitable 46% dry weight. Adrenalectomy, which has been restore body mass normal, had effect returning rate muscle control values. Insulin at...

The study aimed to investigate arterial stiffness in subjects with normal glucose tolerance.BMI, systolic blood pressure, fasting plasma glucose, lipid variables, ankle-brachial pressure index and brachial-ankle pulse wave velocity were measured 2059 from Takasaki city, located approximately 100 km north of Tokyo Japan. Following a 75-g oral tolerance test, only selected.One-hour post-challenge levels correlated values (r = 0.340, P < 0.0001). When divided into three groups-group 1 (1-h 8.56...

Free triiodothyronine/free thyroxine (FT3/FT4) ratio is considered as an index of the activities iodothyronine deiodinase types 1 and 2 (DIO1 DIO2, respectively) reportedly associated with insulin resistance in euthyroid adults. Euthyroid women polycystic ovary syndrome accompanied have lesser activities. Correspondingly, serum level a fasted condition positively correlates FT3/FT4 ratio, depletion decreases DIO2 activity mice. Selected genetic variants DIO1 are also measures. Therefore, if...

Screening of medical students and international for tuberculosis (TB) at the time admission is a key strategy to control prevent spread infection on university campus teaching hospitals because high risk exposure TB patients. The Mycobacterium antigen-specific T-cell interferon-γ release assays (IGRAs) are specific latent detection methods used in such groups. Currently, Japan, there no guidelines baseline data IGRAs evaluate these high-risk In order schools retrospective study was...

Glucose-dependent insulinotropic polypeptide (GIP), a peptide released from the intestines after meals, is thought to stimulate insulin secretion. GIP receptor cDNA has recently been cloned and its mRNA recognized in several organs including pituitary, but physiological roles of receptors pituitary have yet be determined. We demonstrated possibility that stimulates GH secretions adenoma cells acromegalics. GIP-stimulated responses were studied four In two acromegalics whose showed...