Cellular and molecular cues of glucose sensing in the rat olfactory bulb

Abstract

In the brain, glucose homeostasis of extracellular fluid is crucial to the point that systems specifically dedicated to glucose sensing are found in areas involved in energy regulation and feeding behavior. Olfaction is a major sensory modality regulating food consumption. Nutritional status in turn modulates olfactory detection. Recently it has been proposed that some olfactory bulb (OB) neurons respond to glucose similarly to hypothalamic neurons. However, the precise molecular cues governing glucose sensing in the OB are largely unknown. To decrypt these molecular mechanisms, we first used immunostaining to demonstrate a strong expression of two neuronal markers of glucose-sensitivity, insulin-dependent glucose transporter type 4 (GLUT4), and sodium glucose co-transporter type 1 (SGLT1) in specific OB layers. We showed that expression and mapping of GLUT4 but not SGLT1 were feeding state-dependent. In order to investigate the impact of metabolic status on the delivery of blood-borne glucose to the OB, we measured extracellular fluid glucose concentration using glucose biosensors simultaneously in the OB and cortex of anesthetized rats. We showed that glucose concentration in the OB is higher than in the cortex, that metabolic steady-state glucose concentration is independent of feeding state in the two brain areas, and that acute changes in glycemic conditions affect bulbar glucose concentration alone. These data provide new evidence of a direct relationship between the OB and peripheral metabolism, and emphasize the importance of glucose for the OB network, providing strong arguments toward establishing the OB as a glucose-sensing organ.

The incretin hormone glucagon‐like peptide 1 increases mitral cell excitability by decreasing conductance of a voltage‐dependent potassium channel

“…) and glucose transporters such as sodium‐glucose transport protein‐1 or insulin sensitive, glucose transporter 4 (Al Koborssy et al . ), of which the latter is known to be regulated by Kv1.3 (Xu et al . ).…”

High Fructose Diet inducing diabetes rapidly impacts olfactory epithelium and behavior in mice

“…However, behavioral alterations will definitely also be due to changes at more central levels. For instance, the olfactory bulb will be modulated by HFruD since it is extremely sensitive to insulinemia and glycemia 44 45 . The entire OB network and more specifically mitral cells should be modulated 46 .…”

Mitochondrial Ultrastructure and Glucose Signaling Pathways Attributed to the Kv1.3 Ion Channel

“…Postprandially when glucose levels in the blood are high, GLUT4 is expressed on the plasma membrane of dendritic processes. GLUT4 in fasted rats however, is internalized into the cytoplasm (Al Koborssy et al, 2014 ) even though insulin levels in the OB are shown to be 15 fold higher in the fasting state (Fadool et al, 2000 ). Our biochemical data point to a role of Kv1.3 in controlling GLUT4 expression on the membrane but more evidence is needed to prove that this modulation could bypass IR kinase in vivo .…”

“…In adipocytes, the mechanism of translocation is thought to occur through a PI3K-independent pathway consisting of depolarizing the plasma membrane and increasing the intracellular Ca 2+ concentration (Li et al, 2006 ). The co-localization of GLUT4 and Kv1.3 centrally has not been explored and the mechanism of glucose signaling in the OB has only recently been investigated (Tucker et al, 2013 ; Al Koborssy et al, 2014 ) for such an energy demanding process as odor processing (Carter and Bean, 2009 ; Lecoq et al, 2009 , 2011 ). Kv1.3 currents can be modulated by metabolically active (d-glucose) rather than inactive (l-glucose) glucose in a dose-dependent manner that follows a bell-shaped curve (Tucker et al, 2013 ).…”