Figure 3.

Midsagittal view of the rat brain presenting the proposed involvement of orexin neurons in the control of the daily plasma glucose rhythm. (i) Orexin-containing neurons in the perifornical area (PF) are innervated by both glutamatergic and GABAergic projections from the biological clock (SCN). During the main part of the light period, activation of the orexin neurons by the excitatory glutamatergic inputs is prevented by the simultaneous release of the inhibitory neurotransmitter GABA (the daily activity pattern of these inputs is indicated by the lines in the yellow/blue boxes aside the projections). The circadian withdrawal of the GABAergic input at the end of the light period allows the orexin neurons to become active at the onset of darkness. (ii) Subsequently, the excitatory effect of orexin on the preganglionic neurons in the intermediolateral column (IML) of the spinal cord will (iii) activate the sympathetic input to the liver and result in increased hepatic glucose production. Orexin also stimulates glucose uptake in skeletal muscle via an action in the VMH and mediated through the sympathetic nervous system [80]; but, as it is not clear yet how this message is propagated from the VMH to the autonomic nervous system, this action has not been incorporated in this schema. Possibly the effect of orexin in the VMH on glucose uptake is mediated via VMH projections to the pre-autonomic neurons in the PVN. Moreover, also the effect of orexin on hepatic glucose production might in fact in involve a projection of the PF orexin neurons to the pre-autonomic neurons in the PVN, instead of, or in addition to, the direct projection of the PF orexin neurons to the spinal cord as drawn in the figure.

Adapted from Ref. [152].