Muscle-specific overexpression of heparin-binding epidermal growth factor-like growth factor increases peripheral glucose disposal and insulin sensitivity.

Physical exercise ameliorates metabolic disorders such as type 2 diabetes mellitus and obesity, but the molecular basis of these effects remains elusive. In the present study, we found that exercise up-regulates heparin-binding epidermal growth factor-like growth factor (HB-EGF) in skeletal muscle. To address the metabolic consequences of such gain of HB-EGF function, we generated mice that overexpress this protein specifically in muscle. The transgenic animals exhibited a higher respiratory quotient than did wild-type mice during indirect calorimetry, indicative of their selective use of carbohydrate rather than fat as an energy substrate. They also showed substantial increases in glucose tolerance, insulin sensitivity, and glucose uptake by skeletal muscle. These changes were accompanied by increased kinase activity of Akt in skeletal muscle and consequent inhibition of Forkhead box O1-dependent expression of the pyruvate dehydrogenase kinase 4 gene. Furthermore, mice with a high level of transgene expression were largely protected from obesity, hepatic steatosis, and insulin resistance, even when maintained on a high-fat diet. Our results suggest that HB-EGF produced by contracting muscle acts as an insulin sensitizer that facilitates peripheral glucose disposal.

[Reversible left ventricular dysfunction manifesting as hyperkinesis of the basal and the apical areas with akinesis of the mid portion: a case report].

A 60-year-old man underwent emergent cardiac catheterization because of anterior chest oppression. He had been treated with calcium antagonist and nitrate. Coronary angiography showed no organic stenosis. However, left ventriculography revealed that the basal and the apical areas were hyperkinetic and the mid portion was akinetic. Echocardiography showed that the bizarre-shaped left ventricular dysfunction had completely recovered after a week. Serial electrocardiography demonstrated initial ST-segment elevation in the precordial leads followed by T-wave inversion in II, III, a VF and V4-V6. Coronary artery spasm provocation tests were negative. Endomyocardial biopsy revealed focal myocardial depletion and mild fibrosis. The present case may be an atypical form of tako-tsubo-like left ventricular dysfunction in which the left ventricular contraction is symmetric with both hyperkinetic and akinetic areas.