No abstract

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.

Introduction of STAT3-C markedly increased the luciferase activity in WM1205Lu cells transfected with reporter vectors linked to the 5¢-flanking region of the IL-8 gene from -546 to +44 base pair (bp) and from -272 to +44 bp, but not in cells expressing reporter plasmids from -133 to +44 bp and from -98 to +44 bp. These results indicate that the upregulation of IL-8 production is caused by constitutive STAT3 activation at the level of gene transcription in melanoma cells.

Ratios of young platelets or reticulated platelets can be routinely obtained as an immature platelet fraction (IPF) with the XE-2100 automated hematology analyzer (Sysmex, Kobe, Japan). We combined IPF analysis of 31 patients with myelodysplastic syndrome (MDS) with a complete blood count, a bone marrow examination, and a chromosome analysis. The patients with >40 x 10(9)/L platelets were classified as group A, and those with > or =40 x 10(9)/L were placed in group B. The 2 groups were subclassified as A1 or B1 for patients with an IPF of <10% and as A2 or B2 for those with an IPF > or =10%. Categories A1, A2, B1, and B2 comprised 12 patients, 6 patients, 7 patients, and 6 patients, respectively. Patients with a relatively high IPF (>10%) (category A2 or B2) showed distinctive characteristics. Group B2 showed a higher frequency of chromosomal abnormalities than B1 (P = .029), and group A2 tended to show a higher incidence of clinical improvement than A1 (P = .08). IPF determination may be clinically useful for the assessment of prognosis for MDS patients.