Lineage conversion of mouse fibroblasts to pancreatic α-cells

α-cells, which synthesize glucagon, also support β-cell survival and have the capacity to transdifferentiate into β-cells. However, the role of α-cells in pathological conditions and their putative clinical applications remain elusive due in large part to the lack of mature α-cells. Here, we present a new technique to generate functional α-like cells. α-like cells (iAlpha cells) were generated from mouse fibroblasts by transduction of transcription factors, including Hhex, Foxa3, Gata4, Pdx1 and Pax4, which induce α-cell-specific gene expression and glucagon secretion in response to KCl and Arg stimulation. The cell functions in vivo and in vitro were evaluated. Lineage-specific and functional-related gene expression was tested by realtime PCR, insulin tolerance test (ITT), glucose tolerance test (GTT), Ki67 and glucagon immunohistochemistry analysis were done in iAlpha cells transplanted nude mice. iAlpha cells possess α-cell function in vitro and alter blood glucose levels in vivo. Transplantation of iAlpha cells into nude mice resulted in insulin resistance and increased β-cell proliferation. Taken together, we present a novel strategy to generate functional α-like cells for the purposes of disease modeling and regenerative medicine.

Clinical analysis of coronary artery disease in elderly patients with sleep disordered breathing / 南方医科大学学报

<p><b>OBJECTIVE</b>To understand the prevalence of sleep disordered breathing (SDB) in elderly patients with coronary artery disease (CAD) and explore the relations between SDB and CAD.</p><p><b>METHODS</b>Sixty-two elderly patients with and 18 without CAD identified by coronary angiography underwent examinations by polysomnography (PSG). Left ventricular ejection fraction (LVEF) was measured by 99Tc equilibrium radionuclide angiography.</p><p><b>RESULTS</b>In the 62 elderly patients with CAD, 53.2% had SDB, a rate significantly higher that (22.2%) in the 18 non-CAD patients. The CAD patients with SDB had higher respiratory disturbance index (RDI) and body mass index (BMI) and lower arterial saturation of oxygen (SaO2) during sleep, with longer duration of low SPO2 (less that 90%). The incidence of hypertension was higher in CAD patients with SDB than in those without SDB. No significant correlation was found between the severity of coronary artery disease and RDI (r=-0.16, P>0.05).</p><p><b>CONCLUSION</b>The elderly patients with CAD have higher incidence of SDB, and appropriate interventions should be administered in those with severe SDB.</p>

Relationship between chronic congestive heart failure and sleep-disordered breathing in elderly patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To determine the prevalence of sleep disordered breathing (SDB) in elderly patients with chronic congestive heart failure (CHF) and explore the relations between SDB and left ventricular function.</p><p><b>METHODS</b>By means of polysomnography, 56 elderly patients with CHF were divided into non-SDB, mild SDB, moderate SDB, and severe SDB groups, and the left ventricular ejection fraction (LVEF) was measure by (99)Tc equilibrium radionuclide angiography.</p><p><b>RESULTS</b>In the 56 elderly patients with CHF, 38 (67.9%) had SDB, including 12 (21.4%) mild SDB, 14 (25.0%) moderate SDB, and 12 (21.4%) severe SDB patients. Thirty (53.6%) of the 56 patients with CHF had obstructive sleep apnea (OSA), 4 (7.1%) had central sleep apnea and 22 (39.2%) had mixed sleep apnea. The moderate and severe SDB groups had lower minimum arterial oxyhemoglobin saturation during sleep than the non-SDB groups, and the apnea-hyponea index was closely related to LVEF (r=-0.74, P<0.01).</p><p><b>CONCLUSION</b>The prevalence of SDB, predominantly OSA, is high in elderly patients with CHF. Moderate and severe SDB might affect the left ventricular function in these patients, who require polysomnography monitoring.</p>