PC-1 content in skeletal muscle of non-obese,non-diabetic subjects: relationship to insulin receptor tyrosine kinase and whole body insulin sensitivity

Summary Insulin sensitivity varies widely in non-obese, non-diabetic subjects, and we have previously reported that in vivo insulin action correlates with in vitro insulin stimulated insulin receptor tyrosine-kinase activity in skeletal muscle. Plasma membrane glycoprotein PC-1 content is elevated in fibroblasts of insulin-resistant subjects, and expression of PC-1 cDNA in cultured cells reduces both insulin receptor tyrosine-kinase activity and the biological actions of insulin. In the present study we investigated non-obese, non-diabetic subjects and found a significant negative correlation between muscle PC-1 content and both in vivo insulin action as measured by the intravenous insulin tolerance test (r=−0.51,p=0.035) and the sensitivity (ED₅₀) of in vitro insulin stimulation of insulin receptor tyrosine-kinase activity (r=0.66,p=0.027). These studies indicate, therefore, that increased muscle PC-1 content is associated with reduced insulin action both in vivo and in vitro. Moreover, they suggest a possible role for PC-1 in regulating insulin receptor function in human skeletal muscle. recipient of a Juvenile Diabetes Foundation Post-Doctoral Fellowship     

Alternatives to psychiatric hospitalization for children

The impetus for the dramatic increase in the number of treatment alternatives for children has come from changes in the theoretical conceptualization of treatment, social and political pressures, and financial considerations. This article reviews the literature on alternatives to hospitalization, appraising the available data on the effectiveness of psychiatric hospitalization and its alternatives and considers future research needs and the development of services in this area.     

The Canadian Chiropractic Examination Board results: a statistical evaluation

This paper presents a statistical analysis of the Canadian Chiropractic Examining Board results for the years 1977, 1978 and 1979. The examinations, of which there are 10, together with the overall result are examined from the point of view of the student’s college of graduation, the year in which the examinations were written and (for CMCC students only) prior non-chiropractic education. Finally the correlation between individual subjects and the final percent is discussed.It was found that both chiropractic college of graduation and the year in which the examinations were written were strongly related to an individual’s standing. Since it is quite possible that these results are an artifact of the examinations, arguments are put forward that the graduate population did indeed vary from year to year, and that systematic differences do exist among the graduates of the various colleges. On the other hand, however, it was found that prior non-chiropractic education had little bearing on how well a graduate did on the examinations.Although there were very strong correlations between the examinations and the final percent, four of these examinations — Neurology, Pathology, Physiology and Principles — together accounted for over 90% of the variance in the final grade.     

Amniotic fluid acetylcholinesterase measurements: comparing immunochemical and polyacrylamide gel techniques

In the present study, a recently reported immunochemical technique for measuring acetylcholinesterase (AChE) in amniotic fluid utilizing the 4F19 antibody was compared with the widely utilized polyacrylamide gel technique to determine whether the immunochemical assay provided an advantage in separating unaffected pregnancies from those associated with open spina bifida (OSB) and open ventral wall defects (OVWD). The study included (1) 73 amniotic fluid samples from unaffected pregnancies [alpha-fetoprotein (AFP) less than 2 MoM] with no visible gel AChE band, (2) nine bloodstained samples from unaffected pregnancies (AFP 2.2-4.0 MoM) with visible gel AChE bands, (3) 18 samples associated with OSB (AFP 2.2-7.0 MoM) with visible gel AChE bands, and (4) 20 samples associated with OVWD (AFP 3.2-53.5 MoM) with visible gel AChE bands. The immunochemical assay produced ranges of measurements in the four respective categories as follows: (1) 2-60 arbitrary units (AU): (2) 14-69 AU, (3) 61-593 AU, and (4) 22-476 AU. Eight of the nine unaffected pregnancies with visible gel AChE bands had immunochemical measurements below the highest measurement for the samples with no visible AChE band (60 AU), as did five out of 20 OVWD pregnancies. Two of the OSB cases had values of 61 and 62 AU. These data indicate that the 4F19 specific monoclonal antibody to AChE is capable of distinguishing unaffected from affected pregnancies with reasonable reliability but that more work needs to be done to establish the extent of overlap between the unaffected and affected populations.     

Does insulin need a second messenger?

It is well established that specific binding sites for insulin are present on the plasma membranes of target tissues. In order to explain how insulin regulates a wide variety of biologic functions both on the surface of the cell as well as in its interior, it has been postulated that insulin generates a second messenger at the cell surface. To date, however, no second messenger for insulin has been identified that can carry out all of insulin's known actions. Recent studies have demonstrated that, in addition to the plasma membrane, other subcellular organelles, such as the nucleus, have specific binding sites for insulin. There is also evidence indicating that large serum proteins such as albumin, large protein hormones such as prolactin, and small protein hormones such as insulin can enter intact cells. It is hypothesized, therefore, that insulin has at least two mechanisms of action on target tissues. One mechanism entails the direct binding of insulin to the plasma membrane, which in turn leads to its well-known effects on membrane transport. The other mechanism requires the entry of insulin itself into the interior of the cell and its subsequent direct binding to subcellular organelles. This latter process then serves to mediate many of the known intracellular functions of insulin.     

The effect of chloroquine on the binding, intracellular distribution, and action of insulin on isolated mouse pancreatic acini

The effects of chloroquine on the binding, intracellular distribution, and action of insulin were studied in isolated pancreatic acini prepared from diabetic mice. Chloroquine had three effects on these cells. First, chloroquine altered cellular morphology by inducing an increase in the number and size of autophagic vacuoles and vesicles in the Golgi-lysosomal region. Second, chloroquine, in a dose-dependent fashion, increased the amount of 125I-insulin associated with acini. A detectable effect of chloroquine was seen at 10 microM, and a maximal effect was seen at 30-100 microM where cell-associated insulin was more than doubled. Employing electron microscope autoradiographs, this accumulation of hormone was observed in the Golgi-lysosome area of the pancreatic acinar cell. Third, chloroquine had selective effects on the action of insulin. Preincubation with chloroquine had no effect on basal [3H]2-deoxy-D-glucose uptake, but in a dose-dependent fashion it decreased the stimulatory effect of insulin on this function; at 100 microM chloroquine, the effect of insulin was abolished. In contrast, chloroquine had negligible effects on the stimulation of 2-deoxy-D-glucose uptake into acini by cholecystokinin. Chloroquine in dose-dependent fashion partially inhibited basal [3H]leucine incorporation into acinar cell protein, but in contrast to its effects on 2-deoxy-D-glucose uptake, the drug had no effects on the stimulation of this function by insulin.+2