Bromocriptine as a Potential Glucose-lowering Agent for the Treatment of Prolactinoma with Type 2 Diabetes.

A 22-year-old Japanese woman consulted an endocrinologist due to persistent galactorrhea for the past 10 months. She had hyperprolacinemia and had previously been diagnosed with type 2 diabetes mellitus based on her glycohemoglobin level of 11.6%.

Effects of a sodium glucose co-transporter 2 selective inhibitor, ipragliflozin, on the diurnal profile of plasma glucose in patients with type 2 diabetes: A study using continuous glucose monitoring.

Aims/introduction: To assess the effects of sodium glucose co-transporter 2 inhibitor therapy on the pathophysiology of type 2 diabetes.

Materials And Methods: We administered ipragliflozin to 21 inpatients with type 2 diabetes for 7 days, and analyzed the diurnal profiles of plasma glucose and 3-hydroxybutyrate. A total of 21 age-, sex- and body mass index-matched diabetic patients served as controls.

Adding of Sitagliptin on Insulin Therapy Effectively and Safely Reduces a Hemoglobin A1c Level and Glucose Fluctuation in Japanese Patients with Type 2 Diabetes.

Aims. Efficacy and safety of DPP-4 inhibitor, sitagliptin, add-on therapy to insulin were investigated in Japanese patients with type 2 diabetes. Subjects and Methods.

Synergic effects of β-estradiol and erythromycin on hERG currents.

The incidence rates of long QT syndrome (LQTS) and drug-induced torsades de pointes (TDP) are higher in women than men. Although gonadal steroids are assumed to play an important role in the gender-based differences in cardiac electrophysiological properties, the underlying mechanisms of the gender-based differences are not fully understood. In particular IKr, which comprises the repolarization phase of the action potential, has not been well understood in its modulation by sex hormones.

Identification and characterization of the slowly exchanging pH-dependent conformational rearrangement in KcsA.

Gating of ion channels is strictly regulated by physiological conditions as well as intra/extracellular ligands. To understand the underlying structures mediating ion channel gating, we investigated the pH-dependent gating of the K(+) channel KcsA under near-physiological conditions, using solution-state NMR. In a series of (1)H(15)N-TROSY HSQC (transverse relaxation optimized spectroscopy-heteronuclear single quantum coherence) spectra measured at various pH values, significant chemical shift changes were detected between pH 3.

The fundamental properties of Homer 1 in association with cardiac ryanodine receptor in mouse heart.

Background: Homer, known as a scaffolding protein that regulates postsynapse signaling in neurons, has been poorly explored in cardiac research. We show the fundamental properties of Homer 1 in mouse heart in association with cardiac ryanodine receptor (RyR), a binding protein of Homer 1.

Methods And Results: Immunohistochemistry of adult mouse heart with Homer 1 antibody showed striated staining on Z-bands both in atria and ventricles.

ATP autocrine/paracrine signaling induces calcium oscillations and NFAT activation in human mesenchymal stem cells.

Human bone marrow-derived mesenchymal stem cells (hMSCs) have the potential to differentiate into several types of cells. Calcium ions (Ca(2+)) play an important role in the differentiation and proliferation of hMSCs. We have demonstrated that spontaneous [Ca(2+)](i) oscillations occur without agonist stimulation in hMSCs.

Na+/K+ ATPase and its functional coupling with Na+/Ca2+ exchanger in mouse embryonic stem cells during differentiation into cardiomyocytes.

Cardiomyocytes derived from mouse embryonic stem (mES) cells have been demonstrated to exhibit a time-dependent expression of ion channels and signal transduction pathways in electrophysiological studies. However, ion transporters, such as Na+/K+ ATPase (Na+ pump) or Na+/Ca2+ exchanger, which play crucial roles for cardiac function, have not been well studied in this system. In this study, we investigated the functional expression of Na+/K+ ATPase and Na+/Ca2+ exchanger in mES cells during in vitro differentiation into cardiomyocytes, as well as the functional coupling between the two transporters.

Novel C-terminus frameshift mutation, 1122fs/147, of HERG in LQT2: additional amino acids generated by frameshift cause accelerated inactivation.

Objective: The function of the C-terminus region of the human ether-a-go-go related gene (HERG) has not been well characterized except for its involvement in trafficking. To understand further the role of C-terminus region, we performed a functional analysis of a novel frameshift mutation (1122fs/147) identified in a Japanese long QT syndrome 2 (LQT2) patient who had recurrent episodes of syncope.

Methods: Wild type (WT) and mutant HERG plasmids were transfected into human embryonic kidney (HEK-293) cells, and whole-cell current was recorded by the patch-clamp technique.

Truncated KCNQ1 mutant, A178fs/105, forms hetero-multimer channel with wild-type causing a dominant-negative suppression due to trafficking defect.

We identified a novel mutation Ala178fs/105 missing S3-S6 and C-terminus portions of KCNQ1 channel. Ala178fs/105-KCNQ1 expressed in COS-7 cells demonstrated no current expression. Co-expression with wild-type (WT) revealed a dominant-negative effect, which suggests the formation of hetero-multimer by mutant and WT.

Resolution of abnormal body surface maps in children with atrial septal defect after intracardiac repair.

Introduction: The genesis of repolarization abnormalities of ECG waveforms in atrial septal defect (ASD), which typically is characterized by right ventricular (RV) volume overload, has not been explored, particularly in association with postoperative hemodynamic improvement. The aim of this study was to evaluate the effects of reduced RV overload after ASD closure on depolarization and repolarization abnormalities on body surface maps (BSMs).

Methods And Results: BSMs of 14 children with ASD were recorded preoperatively and at early postoperative (1-6 months) and late postoperative (>9 months) stages.

Functional expression of Ca2+ signaling pathways in mouse embryonic stem cells.

Mouse embryonic stem (mES) cells have the potential to differentiate into all types of cells, but the physiological properties of undifferentiated mES cells, including Ca2+ signaling systems, are not fully understood. In this study, we investigated Ca2+ signaling pathways in mES cells by using confocal Ca2+ imaging systems, patch clamp techniques and RT-PCR. The stimulations with ATP and histamine (His) induced a transient increase of intracellular Ca2+ concentration ([Ca2+]i), which were prevented by the pretreatment of 2-amino-ethoxydiphenyl borate (2-APB), a blocker for inositol-1,4,5-triphosphate receptors (InsP3Rs).

Changes in body surface potential distributions induced by isoproterenol and Na channel blockers in patients with the Brugada syndrome.

Background: The characteristics of unique ECG findings in the Brugada syndrome have not been well explained.

Methods: To clarify their characteristics and mechanisms, body surface maps (BSM) were recorded from patients with the Brugada syndrome (13 cases; a mean age of 48 years) before and after administration of isoproterenol (ISP) or Na channel blockers (12 cases).

Results: ST elevation in V1-V3 was decreased by 0.

Block of HERG current expressed in HEK293 cells by the Na+-channel blocker cibenzoline.

A Na(+)-channel blocker, cibenzoline, blocks the delayed rectifier potassium current ( I(k)), but its detailed action on the rapidly activating component ( I(kr)) of I(k) encoded by the human ether-a-go-go-related gene ( HERG) has not been clarified. We examined the effects of cibenzoline on stably expressed HERG current in HEK293 cells recorded by the patch-clamp technique of whole-cell configuration. Cibenzoline blocked HERG current expressed in HEK293 cells with IC(50) = 3.

Structural basis of the KcsA K(+) channel and agitoxin2 pore-blocking toxin interaction by using the transferred cross-saturation method.

We have determined the binding site on agitoxin2 (AgTx2) to the KcsA K(+) channel by a transferred cross-saturation (TCS) experiment. The residues significantly affected in the TCS experiments formed a contiguous surface on AgTx2, and substitutions of the surface residues decreased the binding affinity to the KcsA K(+) channel. Based on properties of the AgTx2 binding site with the KcsA K(+) channel, we present a surface motif that is observed in pore-blocking toxins affecting the K(+) channel.

Regional and frequency-dependent changes in action potentials and transient outward K+ currents in ventricular myocytes from J-2-K cardiomyopathic hamsters.

Objectives: Although lengthening of action potential duration (APD) and decreased transient outward K+ currents (I(to)) have been observed in ventricular myocytes from cardiomyopathic hamsters, epi- and endo-cardial differences in I(to) and their roles in frequency-dependent changes in APD have not been clarified.

Methods: The patch-clamp technique of whole-cell configuration was used to record membrane potentials and currents in epicardial and endocardial myocytes of the J-2 hamster germline without (control) and with cardiomyopathy (CM).

Results: In control, APD in endocardial myocytes was longer than that in epicardial myocytes at 0.

Effects of Na+ channel blocker, pilsicainide, on HERG current expressed in HEK-293 cells.

Purpose: Pilsicainide, classified as a relatively pure Na+ channel blocker, occasionally causes QT prolongation, suggesting inhibitory actions on K+ currents. We studied effects of pilsicainide on the K+ channel current of the human ether-a-go-go-related gene (HERG) in heterologous expression system.

Methods: The Patch-clamp technique in whole-cell configuration was used to record the channel current of HERG stably expressed in HEK293 cells.

Ca(2+) oscillations regulated by Na(+)-Ca(2+) exchanger and plasma membrane Ca(2+) pump induce fluctuations of membrane currents and potentials in human mesenchymal stem cells.

Human bone marrow-derived mesenchymal stem cells (hMSCs) have the potential to differentiate into several types of cells. We have demonstrated spontaneous [Ca(2+)](i) oscillations in hMSCs without agonist stimulation, which result primarily from release of Ca(2+) from intracellular stores via InsP(3) receptors. In this study, we further investigated functions and contributions of Ca(2+) transporters on plasma membrane to generate [Ca(2+)](i) oscillations.

Genetic and ultrastructural demonstration of strong reversibility in human mesenchymal stem cell.

We examined human bone marrow mesenchymal stem cells by applying real-time quantitative polymerase chain reaction (PCR) (RT-PCR) technology and electron-microscopic techniques. Our RT-PCR demonstrated that the values of peroxisome proliferation-activated receptor gamma2 (PPARgamma2) and lipoprotein lipase (LPL) mRNA dramatically increased according to adipogenic stimulation. The expressions of both PPARgamma2 and LPL mRNA were significantly reduced ( P<0.

Calcium-activated CL- current is enhanced by acidosis and contributes to the shortening of action potential duration in rabbit ventricular myocytes.

Ca2+-activated Cl- current (I(Cl(Ca))) is activated by Ca2+ transient via Ca2+-induced Ca2+ release from sarcoplasmic reticulum in cardiac myocytes and is supposed to play an important role in the repolarization of action potential. It is not well understood, however, how I(Cl(Ca)) is modulated to affect action potential in normal or pathological conditions. In this study we examined the effects of external acidosis on I(Cl(Ca)) and action potential.

Moving dipole analysis of normal and abnormal ventricular activation by magnetocardiography.

The current source during ventricular excitation of the in situ heart has not been well characterized. We analyzed current dipoles of ventricular excitation by magnetocardiography (MCG) in 16 healthy subjects and 10 patients with the Wolff-Parkinson-White syndrome or premature ventricular contraction. Single current dipoles were estimated by MCG with the spatial position, direction, and strength in the initial 40 ms of QRS (moving dipole analysis).