Endocrinology
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Previous work suggests that normal GLUT4 content is sufficient for increases in muscle glucose uptake (MGU) during hyperinsulinemia, because glucose phosphorylation is the more formidable barrier to insulin-stimulated MGU. It was hypothesized that a partial ablation of GLUT4 would not impair insulin-stimulated MGU when glucose phosphorylation capacity is normal but would do so when glucose phosphorylation capacity is increased. Thus, chow-fed C57BL/6J mice with a GLUT4 partial knockout (GLUT4(+/-)), hexokinase II overexpression (HK(Tg)), or both (HK(Tg) + GLUT4(+/-)) and wild-type littermates were studied. ⋯ However, the enhanced insulin-stimulated R(g) created by HK overexpression was ablated in HK(Tg) + GLUT4(+/-) mice. Thus, a 50% reduction of normal GLUT4 content in the presence of normal HK activity does not impair insulin-stimulated MGU. However, when the glucose phosphorylation barrier is lowered by HK overexpression, GLUT4 availability becomes a limitation to insulin-stimulated MGU.
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Central glucostasis is a critical monitored variable in neuroendocrine regulation of pituitary LH secretion. Glucoprivic signals originating within the caudal hindbrain suppress LH. Septopreoptic mu opioid receptors (mu-R) function within neural pathways maintaining basal LH levels and mediate the effects of diverse physiological stimuli on hormone release. ⋯ Dual immunocytochemical labeling for septopreoptic mu-R-ir and Fos-ir demonstrated a robust induction of Fos expression by receptor-positive neurons within discrete septopreoptic sites in response to CV4 5TG, a genomic response that was diminished by CTOP pretreatment. The current studies provide novel evidence for the transcriptional activation of neuroanatomically characterized, mu-R-expressing neurons by decreased hindbrain glucose utilization and show that the functional status of mu-R is critical for maximal induction of the Fos stimulus-transcription cascade in these cells by central glucoprivic signaling. The finding that receptor antagonist-mediated suppression of this genomic response is correlated with increased reproductive neuroendocrine output supports a role for these discrete mu-R-expressing neuron populations as substrates for ligand regulatory effects on the GnRH-pituitary LH axis during neuroglucopenia.