Insulin resistance and increased pancreatic beta-cell proliferation in mice expressing a mutant insulin receptor (P1195L).

Several mutations of the tyrosine kinase domain of insulin receptor (IR) have been clinically reported to lead insulin resistance and insulin hypersecretion in humans. However, it has not been completely clarified how insulin resistance and pancreatic beta-cell function affect each other under the expression of mutant IR. We investigated the response of pancreatic beta-cells in mice carrying a mutation (P1195L) in the tyrosine kinase domain of IR beta-subunit. Homozygous (Ir(P1195L/P1195L)) mice showed severe ketoacidosis and died within 2 days after birth, and heterozygous (Ir(P1195L/wt)) mice showed normal levels of plasma glucose, but high levels of plasma insulin in the fasted state and after glucose loading, and a reduced response of plasma glucose lowering effect to exogenously administered insulin compared with wild type (Ir(wt/wt)) mice. There were no differences in the insulin receptor substrate (IRS)-2 expression and its phosphorylation levels in the liver between Ir(P1195L/wt) and Ir(wt/wt) mice, both before and after insulin injection. This result may indicate that IRS-2 signaling is not changed in Ir(P1195L/wt) mice. The beta-cell mass increased due to the increased numbers of beta-cells in Ir(P1195L/wt) mice. More proliferative beta-cells were observed in Ir(P1195L/wt) mice, but the number of apoptotic beta-cells was almost the same as that in Ir(wt/wt) mice, even after streptozotocin treatment. These data suggest that, in Ir(P1195L/wt) mice, normal levels of plasma glucose were maintained due to high levels of plasma insulin resulting from increased numbers of beta-cells, which in turn was due to increased beta-cell proliferation rather than decreased beta-cell apoptosis.

Estimating myocardial damage and the need for surgery in patients with valvular heart disease by Tl-201 SPECT.

Left ventricular myocardial disorders due to volume overload were investigated by Tl-201 myocardial SPECT (Tl-201 SPECT) in patients with aortic or mitral regurgitation, and its utility for timing cardiac valve replacement was studied. There were significant correlations between Tl-201 scores and electrocardiographic changes and the New York Heart Association classification. There also were favorable correlations between Tl-201 scores and the left ventricular end-diastolic dimension and between Tl-201 scores and left ventricular ejection fraction, and a close relationship between the presence of a left ventricular myocardial disorder and left ventricular diameter. These results suggest that myocardial perfusion abnormalities and left ventricular myocardial disorders may accompany left ventricular dilatation owing to volume overload. After valve replacement, left ventricular end-diastolic dimension normalized, and Tl-201 scores improved slightly, suggesting normalization of myocardial perfusion. When moderate or more severe Tl-201 defects are present on Tl-201 SPECT images, in addition to inverted Tl-201 waves on the electrocardiogram or a left ventricular end-diastolic dimension of 65 mm or more, cardiac valve replacement should be considered.

[Surgical repair for pulmonary artery sling on a 46-day-old infant].

Surgical repair on a 46-day-old girl with pulmonary artery sling is reported. She was suffered from dypnea and admitted to a hospital on 12 days after her birth. On chest roentgenogram atelectasis of right lung was found. She had been on respirator since 21 days after her birth. On bronchogram and pulmonary arteriogram, the trachea and right bronchus were compressed and shifted with the anomalous origin of left pulmonary artery which originated from the right pulmonary artery and passed between the trachea and esophagus. These results confirmed the diagnosis of pulmonary artery sling. Hence, she was referred to our hospital for surgical treatment. She underwent surgical repair on 46-day-old. In operation, we chose a mid-sternal splitting incision, and excised 5 mm of ductus arteriosus. Under extracorporeal circulation, the left pulmonary artery was amptated from the right pulmonary artery and pulled back to left side between the trachea and the esophagus. The left pulmonary artery was anastomosed to the main pulmonary artery at the anterior to the left bronchus. She weaned from respirator, and was extubated on the 3rd day after procedure. She recovered uneventfully in post-operative course. On the 24th day after operation she discharged from hospital. On pulmonary perfusion scanning and pulmonary arteriography performed one year after operation, the left pulmonary artery was patient with slightly decreased perfusion in the left lung. Surgical repair for pulmonary artery sling was recognized as high mortality because of frequently associated tracheobronchial anomalies. In the Japanese literature, only 4 patients survived surgically and lived in late stage.(ABSTRACT TRUNCATED AT 250 WORDS)