Effects of exercise training and dietary manipulation on insulin-regulatable glucose-transporter mRNA in rat muscle.

Both exercise training and dietary manipulation (increasing omega-3/omega-6 fat ratio) can ameliorate insulin resistance caused by a high-fat diet in rats. We determined whether alterations in the expression of the insulin-regulatable (IR) and/or HepG2 glucose-transporter (GT) mRNAs were similarly affected. There was a significantly higher level of IRGT mRNA in skeletal muscle from exercise-trained versus sedentary high-fat-fed rats (27% increase, P less than 0.01). This difference is consistent with previously reported increases in muscle insulin-mediated glucose uptake. Skeletal muscle HepG2GT mRNA was too low to detect any training effect, but there was a tendency toward higher levels with training in cardiac muscle. In contrast, dietary manipulation, previously shown to lead to a much greater increase (100-300%) in muscle insulin-mediated glucose uptake, did not change IRGT or HepG2GT mRNA in skeletal muscle or heart. Thus, both dietary manipulation and exercise training increase insulin-stimulated glucose uptake in skeletal muscle, but only exercise training increases IRGT mRNA. Therefore, exercise training apparently increases GT production, whereas dietary manipulation improves glucose transport in skeletal muscle by other mechanisms.

Evaluation of CD5-positive B cells in blood and synovial fluid of patients with rheumatic diseases.

CD5 (OKT1, Leu-1) is an antigen originally associated only with T cells. This antigen has recently been detected on a population of B cells that have been implicated in autoimmune diseases, particularly in rheumatoid arthritis (RA). We determined the percentage of these cells in the peripheral blood (PB) and synovial fluid (SF) of patients with RA and other joint diseases (OJD) using flow cytometry and two-colour fluorescence. No significant difference was observed between the percentages of CD5-positive B cells in the PB of these two patient groups or healthy individuals. In comparison with PB, significantly higher percentages of these cells were observed in the SF of patients with RA, but not in SF of OJD patients. Higher percentages of B cells were also noted in RA SF. However, when B-cell percentages were accounted for, no significant difference was observed between the numbers of B cells expressing CD5 in SF. No correlation was observed between the percentages of CD5-positive B cells and the levels of rheumatoid factor (RF) or C-reactive protein (CRP). We conclude that CD5-positive B cells are an integral part of the B-cell pool of PB and that there is increased representation of B cells in SF. The increased percentages of B cells in RA SF, compared with OJD, may reflect the autoimmune phenomenon occurring in the rheumatoid joint.

The management of diabetes in adolescents and young adults: a preliminary case study.

This paper describes one part of a first-stage study concerned with the care received by a group of adolescents and young adults with insulin-dependent diabetes mellitus (IDDM) in one district health authority. The paper reports findings from a self-selected sample of 30 patients aged between 15 and 25. Each of the 30 patients was interviewed during a routine appointment at a diabetes clinic. The patients' doctor at the clinic and one of the diabetes specialist nurses also filled in a short questionnaire for each of the patients interviewed. The main finding was that although all 30 patients interviewed reported that their diabetes control was at least moderately good, a significant number of patients had blood glucose levels above the recommended norm. The study lends support to the widely held belief that young adults with diabetes have particular difficulties in maintaining blood glucose levels within a normal range. It is suggested that processes within the current mode of care may be contributing to this poor level of control. Recommendations for a controlled trial of specialist nurse versus doctor care are made.

Glucose transporters and in vivo glucose uptake in skeletal and cardiac muscle: fasting, insulin stimulation and immunoisolation studies of GLUT1 and GLUT4.

Our aim was to study glucose transporters GLUT1 and GLUT4 in relation to in vivo glucose uptake in rat cardiac and skeletal muscle. The levels of both transporters were of a similar order of magnitude in whole muscle tissue (GLUT1/GLUT4 ratio varied from 0.1 to 0.6), suggesting that both may have an important physiological role in regulating muscle glucose metabolism. GLUT4 correlated very strongly (r2 = 0.97) with maximal insulin-stimulated glucose uptake (Rg' max., estimated using the glucose clamp plus 2-deoxy[3H]glucose bolus technique) in six skeletal muscles and heart. A distinct difference in regulation of the two transporters was evident in heart: in 5 h-fasted rats, basal glucose uptake and GLUT1 levels in heart were very high and both were reduced, by 90 and 60% respectively, by 48 h fasting. However, in heart (and in red skeletal muscle), neither GLUT4 levels nor Rg' max. were reduced by 48 h fasting. GLUT1 was shown to be specifically expressed in cardiac myocytes, because intracellular vesicles enriched in GLUT4 contained significant levels of GLUT1. In conclusion, the high association of muscle GLUT4 content with insulin responsiveness in different muscles, and the preservation of both with fasting, supports a predominant role of GLUT4 in insulin-mediated glucose uptake. GLUT1 may play an important role in mediating cardiac muscle glucose uptake in the basal metabolic state. Marked changes in GLUT1 expression with alterations in the metabolic state, such as prolonged fasting, may play an important role in cardiac glucose metabolism.