The brain requires glucose for its normal physiologic function. It has evolved neurons which both sense and regulate peripheral glucose metabolism and energy balance. Such glucose responsive neurons utilize an ATP-sensitive K+ channel (Katp) to increase firing rate when glucose availability increases. Dr. Levin will use a molecular probe (Kir6.2) as a marker for these neurons to investigate the ways the brain monitors and regulates glucose metabolism in healthy animals and why this glucosensing is often dysfunctional in diabetics. A rat model of diet-induced obesity will be used as a model of non-insulin-dependent diabetes (NIDDM). Streptozotocin will be used to induce insulin-dependent diabetes (IDDM) in the presence or absence of repeated bouts of insulin-induced hypoglycemia. In his first specific aim Dr. Levin will assess the cellular location and anatomical distribution of the Kir6.2 on brain neurons by in situ hybridization. The effect of diabetes and selective neurotoxins for glucosensing neurons will be studied as clues to the regulation of Kir6.2 expression in disorders of glucose metabolism and body weight regulation. Next, he will assess the local vs. systemic effects of altering glucose availability on the release of brain catecholamines. This will be done with combinations of cerebral microdialysis with local, forebrain or systemic manipulation of glucose availability in both normal and diabetic rats. Finally, Dr. Levin will assess the way in which diabetes affects the autonomic responses which result when glucose availability is altered in specific autonomic effector areas of the hypothalamus. These studies are expected to provide important insights into the ways in which the brain regulates glucose metabolism in health and disease.
| Levin, Barry E (2017) 10 lessons learned by a misguided physician. Physiol Behav 176:217-222 |
| Otlivanchik, Oleg; Sanders, Nicole M; Dunn-Meynell, Ambrose et al. (2016) Orexin signaling is necessary for hypoglycemia-induced prevention of conditioned place preference. Am J Physiol Regul Integr Comp Physiol 310:R66-73 |
| Le Foll, Christelle; Dunn-Meynell, Ambrose A; Miziorko, Henry M et al. (2015) Role of VMH ketone bodies in adjusting caloric intake to increased dietary fat content in DIO and DR rats. Am J Physiol Regul Integr Comp Physiol 308:R872-8 |
| Magnan, Christophe; Levin, Barry E; Luquet, Serge (2015) Brain lipid sensing and the neural control of energy balance. Mol Cell Endocrinol 418 Pt 1:3-8 |
| Le Foll, Christelle; Dunn-Meynell, Ambrose A; Levin, Barry E (2015) Role of FAT/CD36 in fatty acid sensing, energy, and glucose homeostasis regulation in DIO and DR rats. Am J Physiol Regul Integr Comp Physiol 308:R188-98 |
| Le Foll, Christelle; Dunn-Meynell, Ambrose A; Miziorko, Henri M et al. (2014) Regulation of hypothalamic neuronal sensing and food intake by ketone bodies and fatty acids. Diabetes 63:1259-69 |
| Song, Zhilin; Levin, Barry E; Stevens, Wanida et al. (2014) Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors. Am J Physiol Regul Integr Comp Physiol 306:R447-56 |
| Le Foll, Christelle; Dunn-Meynell, Ambrose; Musatov, Serguei et al. (2013) FAT/CD36: a major regulator of neuronal fatty acid sensing and energy homeostasis in rats and mice. Diabetes 62:2709-16 |
| McNay, Ewan C; Teske, Jennifer A; Kotz, Catherine M et al. (2013) Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: a model for weight gain with intensive insulin therapy. Am J Physiol Endocrinol Metab 304:E131-8 |
| Moullé, Valentine S; Le Foll, Christelle; Philippe, Erwann et al. (2013) Fatty acid transporter CD36 mediates hypothalamic effect of fatty acids on food intake in rats. PLoS One 8:e74021 |
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