Glucose and insulin increase the transport of leptin through the blood-brain barrier in normal mice but not in streptozotocin-diabetic mice

Since fasting is one of the few factors found to change the rate of entry o f leptin into brain, we used multiple-time regression analysis to study the effects of pretreatment with glucose or insulin on leptin transport across the blood-brain barrier (BBB). Two hours after intraperitoneal injection o f glucose (3 g/kg), there was a statistically significant increase in the e ntry rate (K-i) of leptin in fasted (from 4.91 +/- 0.70 x 10(-4) ml/g min t o 9.03 +/- 1.00 x 10(-4) ml/g min) but not (p = 0.15) in nonfasted normal ( from 4.90 +/- 1.21 x 10(-4) ml/g min to 6.42 +/- 1.79 x 10(-4) ml/g min) or fasted streptozotocin (STZ)-treated diabetic mice (from 4.043 +/- 0.959 x 10(-4) ml/g min to 5.395 +/- 1.355 x 10(-4) ml/g min). Insulin (10 U/kg) in creased leptin influx in fasted (from 4.77 +/- 0.26 x 10(-4) ml/g min to 10 .6 +/- 0.15 x 10(-4) ml/g min at 0.5 h) and nonfasted (from 4.64 +/- 0.75 x 10(-4) ml/g min to 7.46 +/- 1.48 x 10(-4) ml/g min at 0.5 h) normal mice, but not in STZ-diabetic mice deficient in insulin (and leptin), even though basal concentrations of glucose were similarly increased in the nonfasted normal and STZ-treated mice. Moreover, the basal rate of leptin influx was the same in overnight fasted normal mice, nonfasted normal mice and STZ-dia betic mice. The results indicate that glucose and insulin can increase lept in transport, but they probably are not the principal factors responsible f or the regulatory effect of the BBB on leptin entry into the brain. Copyrig ht (C) 2001 S. Karger AG. Basel.