Striatal DAT availability does not change after supraphysiological glucose loading dose in humans

Abstract

Brain dopamine neurotransmission is regulated by the dopamine transporter (DAT), which drives reuptake of extracellular dopamine into the presynaptic neurons. We hypothesized that the glucose loading dose would affect the striatal DAT availability. An i.v. bolus injection of 18F-FP-CIT was administered after infusion of low-dose glucose (300 mg/kg), high-dose glucose (600 mg/kg) or placebo (normal saline). The emission data were acquired over 90 min in 23 healthy male subjects. Substantial increases of binding potential (BPNDs) from ventral striatum (VST), caudate nucleus, and putamen were observed after low-dose glucose loading (+26.0, +87.0, and +37.8%) and after high-dose glucose loading (+10.4, +51.9, and +22.0%). BPNDs of the caudate nucleus and putamen showed significant differences (P = 0.0472 and 0.0221) after placebo, low-dose glucose, and high-dose glucose loading. BPNDs in the caudate nucleus and putamen after placebo, low-dose glucose, and high-dose glucose loading were positively intercorrelated with each other. In conclusion, striatal DAT changes after physiological glucose loading, but not after supraphysiological glucose loading in humans. DAT availabilities after placebo, low-dose glucose, high-dose glucose loading were correlated to each other in the caudate nucleus and putamen, but not in the VST. Therefore, sub-regional variability in DAT regulatory mechanisms mediated by insulin may exist in humans.

Keywords: dopamine plasma membrane transport proteins; glucose; insulin; obesity.

Figure 1

Study design.

Figure 2

The average binding potential (BP_ND) after placebo, low-dose glucose, and high-dose glucose loading.

Figure 3

The repeated-measures ANOVA of binding potential (BP_ND) after placebo, low-dose glucose, and high-dose glucose loading from (A) ventral striatum, (B) caudate nucleus, and (C) putamen.

Figure 4

Correlations of BP_NDs after placebo, low-dose glucose, and high-dose glucose loading from (A) ventral striatum, (B) caudate nucleus, and (C) putamen.