Olfactory receptor neurons (ORNs) express a single olfactory receptor (OR) to recognize odorants. Once an odorant ligand is bound to the OR, odorant-evoked neural activity is generated to drive olfactory perception. Each OR characterizes a different pattern of spontaneous ORN activity in the absence of odorant stimulation and both basal and odorant-induced activities play important roles in ORN maturation and odor perception.
Diabetes disturbs glucose metabolism and a changed metabolic status can alter odor perception. Insulin is involved in neural survival as a neural growth factor and may modulate ORN activity. However it remains unclear how diabetes, in particular type 1, changes the neural activity and the odor response properties of ORNs. We examined the effects of hypoinsulinemia on the odorant response properties and ORN activity using a drug-induced type 1 diabetic mouse model that lacks insulin. We used the suction pipette technique to examine activity of ORNs expressing specific ORs, using mouse lines that express GFP in ORNs that express the mOR-EG- or I7-OR. 3 months of diabetes did not induce any significant structural changes of the olfactory epithelium. But in diabetic mice I7-expressing ORNs showed a significant reduction of basal activity when compared to control mice, but those expressing the mOR-EG OR, which already have a low basal activity, did not. In the ligand-evoked responses, the maximal current responses of ORNs expressing mOR-EG- or I7 OR were not significantly different between control and diabetic mice. But the responses of I7 ORNs in diabetic mice decayed much more rapidly, while those of mOR-EG ORNs did not. Similarly, the odorant response recorded by electroolfactogram decayed more rapidly without significant reduction of the maximal response in diabetic mice. These results suggest that type 1 diabetes can alter odorant perception beginning in the periphery and that changes in the ORN activity are OR-dependent.