Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes.

AIMS/HYPOTHESIS: Pregnancy is characterised by temporarily increased insulin resistance. Gestational diabetes occurs when pancreatic beta cell function is unable to compensate for this insulin resistance. Retinol-binding protein 4 (RBP4) could be related to insulin resistance. We hypothesised that RBP4 is elevated in gestational diabetes. METHODS: Serum RBP4, transthyretin and retinol were cross-sectionally measured in 42 women with gestational diabetes and 45 pregnant controls. Of these, 20 women with and 22 without gestational diabetes were included in an additional longitudinal study. RBP4 was determined by enzyme immunometric assay (EIA) and western blot. RESULTS: Women with gestational diabetes had lower RBP4 EIA and western blot levels than controls (median 6.8 [interquartile range, 3.9-14.3] vs 11.3 [7.8-19.9] microg/ml, p < 0.001 and 25.1 [21.7-29.6] vs 26.6 [23.5-32.2] microg/ml, p = 0.026). Transthyretin and the RBP4:transthyretin molar ratio were comparable between the groups. Serum retinol was lower (p < 0.001) and the RBP4 Western blot level: retinol molar ratio was higher in women with gestational diabetes (p = 0.044). RBP4 was not associated with the glucose or homeostasis model assessment of insulin resistance (HOMA-IR), but in gestational diabetes the RBP4:retinol molar ratio correlated with blood glucose and negatively with 2 h post-load insulin. The RBP4:transthyretin ratio correlated with HOMA-IR and fasting insulin in controls. In women with gestational diabetes RBP4 EIA and western blot levels increased after delivery. Retinol increased in both groups, while transthyretin and the RBP4:transthyretin ratio were not altered after parturition. CONCLUSIONS/INTERPRETATION: RBP4 measured by two different techniques is not elevated, but the RBP4:retinol molar ratio is higher and correlates with fasting blood glucose in women with gestational diabetes. Thus, the RBP4:retinol ratio and the RBP4:transthyretin ratio are more informative than RBP4 levels alone when assessing insulin-glucose homeostasis during pregnancy.

PPARalpha deficiency reduces insulin resistance and atherosclerosis in apoE-null mice.

PPARalpha is a ligand-dependent transcription factor expressed at high levels in the liver. Its activation by the drug gemfibrozil reduces clinical events in humans with established atherosclerosis, but the underlying mechanisms are incompletely defined. To clarify the role of PPARalpha in vascular disease, we crossed PPARalpha-null mice with apoE-null mice to determine if the genetic absence of PPARalpha affects vascular disease in a robust atherosclerosis model. On a high-fat diet, concentrations of atherogenic lipoproteins were higher in PPARalpha(-/-)apoE(-/-) than in PPARalpha(+/+)apoE(-/-) mice, due to increased VLDL production. However, en face atherosclerotic lesion areas at the aortic arch, thoracic aorta, and abdominal aorta were less in PPARalpha-null animals of both sexes after 6 and 10 weeks of high-fat feeding. Despite gaining as much or more weight than their PPARalpha(+/+)apoE(-/-) littermates, PPARalpha(-/-)apoE(-/-) mice had lower fasting levels of glucose and insulin. PPARalpha-null animals had greater suppression of endogenous glucose production in hyperinsulinemic clamp experiments, reflecting less insulin resistance in the absence of PPARalpha. PPARalpha(-/-)apoE(-/-) mice also had lower blood pressures than their PPARalpha(+/+)apoE(-/-) littermates after high-fat feeding. These results suggest that PPARalpha may participate in the pathogenesis of diet-induced insulin resistance and atherosclerosis.

Maturation of gait dynamics: stride-to-stride variability and its temporal organization in children.

In very young children, immature control of posture and gait results in unsteady locomotion. In children of approximately 3 yr of age, gait appears relatively mature; however, it is unknown whether the dynamics of walking change beyond this age. Because stride dynamics depend on neural control, we hypothesized that motor control would continue to develop beyond age 3. To test this hypothesis, we measured the gait cycle duration on a stride-by-stride basis in 50 healthy 3- to 14-yr-old children (25 girls). Measurements of stride-to-stride variability were significantly larger both in the 3- and 4-yr-old children, compared with the 6- and 7-yr-old children, and in the 6- and 7-yr-old children, compared with the 11- to 14-yr-old children. Measurements of the temporal organization of gait also revealed significant age-dependent changes. The effects of age persisted even after adjusting for height. These findings indicate that mature stride dynamics may not be completely developed even in healthy 7-yr-old children and that different aspects of stride dynamics mature at different ages.

Motion detection on flashed, stationary pedestal gratings: evidence for an opponent-motion mechanism.

Contrast thresholds were measured for discriminating left vs right motion of a vertical, 1 c/deg luminance grating lasting for one cycle of motion. This test was presented on a 1 c/deg stationary grating (pedestal) of twice-threshold, flashed for the duration of the test motion. Lu and Sperling [(1995). Vision Research, 35, 2697-2722] argue that the visual system detects the underlying, first-order motion of the test and is immune to the presence of the stationary pedestal (and the 'feature wobble' which it induces). On the contrary, we observe that the stationary pedestal has large effects on motion detection at 7 and 15 Hz, and smaller effects at 0.9-3.7 Hz, evidenced by a spatial phase dependency between the stationary pedestal and moving test. At 15 Hz the motion threshold drops as much as five-fold, with the stationary pedestal in the optimal spatial phase (i.e., pedestal and test spatially in phase at middle of motion), and the perceived direction of the test motion reverses with the pedestal in the opposite phase. Phase dependency was also explored using a very brief (approximately 1 msec) static pedestal presented with the moving test. The pedestal of Lu and Sperling (flashed for the duration of the test) has a broad spectrum of left and right moving components which interact with the moving test. The pedestal effects can be explained by the visual system's much higher sensitivity to the difference of the contrast of right vs left moving components than to either component alone.