Effects of unilateral nigrostriatal dopamine depletion on peripheral glucose tolerance and insulin signaling in middle aged rats

Clinical studies indicate an increased incidence of impaired glucose tolerance in individuals with Parkinson's disease (PD). The mechanisms that underlie this co-morbidity are currently unknown. The purpose of this study was to analyze peripheral glucose tolerance following severe unilateral nigrostriatal dopamine (DA) depletion, and to determine whether central and peripheral insulin signaling was affected in the 6-hydroxydopamine (6-OHDA) middle-aged rat model of PD. Although serum insulin levels differed significantly between the 6-OHDA and sham groups over the course of a glucose tolerance test six weeks post-lesion, no significant effect on glucose tolerance or insulin signaling in skeletal muscle was observed. In contrast, markers of striatal insulin resistance were evident in the rats. These data suggest that while 6-OHDA may affect serum insulin levels and striatal insulin signaling, the unilateral 6-OHDA lesion model does not induce glucose intolerance or peripheral insulin resistance, at least at the six-week post-lesion timepoint.

► Severe unilateral dopamine depletion impairs insulin signaling in the striatum.
► Insulin signaling is not affected in muscle.
► Glucose tolerance is not affected in muscle.
► Serum insulin differs slightly between groups following dopamine depletion.