Reduced insulin sensitivity may be related to less striatal glutamate: An ¹H-MRS study in healthy non-obese humans

Levels of striatal dopamine (DA) may be positively correlated with levels of striatal glutamate (Glu). While reduced insulin sensitivity (%S) has been associated with reduced striatal DA levels in healthy non-obese persons, whether reduced %S is also associated with reduced striatal Glu levels has not yet been established. Using ¹H-MRS, we measured levels of several neurometabolites in the striatum and dorsolateral prefrontal cortex (DLPFC) of seventeen healthy non-obese persons (9 female, mean age: 28.35 ± 9.53). Insulin sensitivity was estimated for each subject from fasting plasma glucose and insulin using the Homeostasis Model Assessment II. We hypothesized that %S would be positively related with levels of Glu and Glu + glutamine (Glx) in the striatum. Exploratory analyses were also conducted between other fasting markers of metabolic health and neurometabolites measured with ¹H-MRS. In the right striatum, %S was positively correlated with levels of Glu (r(15) = .49, p = .04) and Glx (r(15) = .50, p = .04). In the left striatum, there was a trend positive correlation between %S and Glu (r(15) = .46, p = .06), but not Glx levels (r(15) = .20, p = .44). The relationships between %S and striatal Glu levels remained after controlling for age, sex, and BMI (right: r(12) = .73, β = .52, t = 2.55, p = .03; left: (r(12) = .63, β = .53, t = 2.25, p = .04) These preliminary findings suggest that %S may be related to markers of glutamatergic functioning in the striatum of healthy non-obese persons. These findings warrant replication in larger samples and extension into neuropsychiatric populations where altered striatal DA, Glu, and %S are implicated.