Insulin sensitivity is inversely related to cellular energy status, as revealed by biotin deprivation

We have reported an early decrease in glycemia in rats fed a biotin-deficient diet with reduced cellular ATP levels, suggesting increased insulin sensitivity. Here, we show that biotin-deprived rats are more tolerant of glucose, as shown by both oral and intraperitoneal glucose tolerance tests, during which insulin plasma levels were significantly diminished in deficient rats compared with controls. Biotin-deficient rats had lower blood glucose concentrations during intraperitoneal insulin sensitivity tests than controls. Furthermore, more glucose was infused to maintain euglycemia in the biotin-deficient rats during hyperinsulinemic euglycemic clamp studies. These results demonstrate augmented sensitivity to insulin in biotin-deprived rats. They are most likely the consequence of an insulin-independent effect of AMPK activation on GLUT4 membrane translocation with increased glucose uptake. In biotin-deficient cultured L6 muscle cells, there was increased phosphorylation of the energy sensor AMPK. We have...