Increased muscle glucose uptake in response to chronic glyburide treatment is not related to changes in glucose transporter (GLUT4) protein.

1. The mechanism of action of glyburide (a sulfonylurea) on muscle has been investigated by measuring glucose uptake and glucose transporter (GLUT4) protein levels after chronic glyburide treatment. 2. A dietary induced insulin resistant rat model (4 wk of high-fat, high-sucrose feeding) was given glyburide (2 mg/kg/day) for 10 days and glucose uptake was measured in a perfused hindquarter preparation. 3. Protein levels of the GLUT4 glucose transporter were determined by Western analysis. 4. After 7 days of treatment, rats fed glyburide had lower blood glucose concentrations 2 hr (72 +/- 5 vs 103 +/- 12 mg/dl) and 24 hr (97 +/- 7 vs 123 +/- 7 mg/dl) after glyburide administration with no difference in serum insulin levels compared to vehicle treated animals. 5. Glucose uptake was approx doubled in basal state (0 insulin) in response to glyburide (2.8 +/- 0.4 vs 1.7 +/- 0.2 mumol/g per hr). 6. Maximal insulin (100 nM) stimulated glucose uptake tended to be higher in the glyburide treated group, but did not reach statistical significance (8.0 +/- 0.7 vs 7.0 +/- 0.6 mumol/g per hr). 7. Western analysis revealed no significant effect of glyburide on the GLUT4 protein level in skeletal muscle. 8. These results suggest that glyburide alters glucose uptake through some mechanism other than alterations in the level of the GLUT4 glucose transporter protein.

Formaldehyde toxicity.

The presence of formaldehyde in biologically active concentrations in several occupational and environmental atmospheres has created concern about the hazards of exposure to these contaminated atmospheres. A review of the clinical and animal toxicologic data demonstrate both primary irritant and sensitizing actions of the compound. The minimal concentration of formaldehyde that can be detected by odor is similar to the level that produces minimal irritant effects on the eyes and in the pulmonary airway, thereby serving as a warning of exposure to the compound. The irritant effects are reversible when exposure is discontinued. Some persons show allergic type responses to concentrations of the compound that are well below the odor threshold. The very limited amount of toxicologic data concerned with effects from prolonged and chronic exposures suggest that the compound does not produce specific delayed types of toxicity. I discuss the factors that influence establishment of "safe" conditions or levels of exposure to formaldehyde.

Acute and prolonged toxicity tests.

An answer to the question of whether acute and prolonged toxicity tests are good candidates for standardization is developed by reviewing (1) the factors that are presumed to influence the results of these tests and (2) the collaborative studies that have been reported in the literature. In regard to acute toxicity tests it is clear that competent laboratories give due consideration for the control of factors that are known to influence these tests. Also competent laboratories using their own procedures provide reliable results, even though the procedures vary from laboratory to laboratory. In regard to prolonged toxicity tests there are no examples of controlled collaborative investigations which could be used to evaluate interlaboratory variation and its relation to the protocols involved. It is recommended that guidelines rather than rigid protocols would be an appropriate approach for improving the quality and accuracy of these toxicologic tests. Examples of such guidelines are given.