Proteome analysis and conditional deletion of the EAAT2 glutamate transporter provide evidence against a role of EAAT2 in pancreatic insulin secretion in mice.

Islet function is incompletely understood in part because key steps in glutamate handling remain undetermined. The glutamate (excitatory amino acid) transporter 2 (EAAT2; Slc1a2) has been hypothesized to (a) provide islet cells with glutamate, (b) protect islet cells against high extracellular glutamate concentrations, (c) mediate glutamate release, or (d) control the pH inside insulin secretory granules. Here we floxed the EAAT2 gene to produce the first conditional EAAT2 knock-out mice. Crossing with Nestin-cyclization recombinase (Cre) eliminated EAAT2 from the brain, resulting in epilepsy and premature death, confirming the importance of EAAT2 for brain function and validating the genetic construction. Crossing with insulin-Cre lines (RIP-Cre and IPF1-Cre) to obtain pancreas-selective deletion did not appear to affect survival, growth, glucose tolerance, or ß-cell number. We found (using TaqMan RT-PCR, immunoblotting, immunocytochemistry, and proteome analysis) that the EAAT2 levels were too low to support any of the four hypothesized functions. The proteome analysis detected more than 7,000 islet proteins of which more than 100 were transporters. Although mitochondrial glutamate transporters and transporters for neutral amino acids were present at high levels, all other transporters with known ability to transport glutamate were strikingly absent. Glutamate-metabolizing enzymes were abundant. The level of glutamine synthetase was 2 orders of magnitude higher than that of glutaminase. Taken together this suggests that the uptake of glutamate by islets from the extracellular fluid is insignificant and that glutamate is intracellularly produced. Glutamine synthetase may be more important for islets than assumed previously.

Differences in birth weight by sex using adjusted quantile distance functions.

Herein, we report results from a study of birth weight distribution among boys and girls born in Norway in 2008. As our primary interest was to detect differences in the variability between the two sexes, we used the quantile distance function to describe the difference between two distribution functions. We used an adjusted version of the quantile function to look into the relation of sex differences in birth weight conditioned on maternal age, gestational age, preeclampsia, maternal diabetes type 1, maternal smoking status, and parity. At term (⩾37 weeks of gestation), boys showed a greater variability in birth weight than did girls, and these differences were maintained in the adjusted model. We also found that maternal age and maternal smoking habits influenced both sexes equally, whereas gestational age, preeclampsia, maternal diabetes type 1, and parity influenced one sex more than the other. The adjusted quantile distance function proved efficient in analyzing and demonstrating how covariates influence sex differences in birth weight.

Greater intrasex phenotype variability in males than in females is a fundamental aspect of the gender differences in humans.

Human studies of intrasex variability have shown that males are intellectually more variable. Here we have performed retrospective statistical analysis of human intrasex variability in several different properties and performances that are unrelated or indirectly related to intelligence: (a) birth weights of nearly 48,000 babies (Medical Birth Registry of Norway); (b) adult weight, height, body mass index and blood parameters of more than 2,700 adults aged 18-90 (NORIP); (c) physical performance in the 60 meter dash event of 575 junior high school students; and (d) psychological performance reflected by the results of more than 222,000 undergraduate university examination grades (LIST). For all characteristics, the data were analyzed using cumulative distribution functions and the resultant intrasex variability for males was compared with that for females. The principal finding is that human intrasex variability is significantly higher in males, and consequently constitutes a fundamental sex difference.