Striatal dopamine transporter changes after glucose loading in humans

Abstract

Aims The dopamine transporter (DAT) actively translocates dopamine that is released from the presynaptic neurons across the membranes of nerve terminals into the extracellular space. We hypothesized that glucose loading‐induced changes in striatal DAT levels could be associated with food intake in humans. Materials and methods An intravenous bolus injection of 18F‐FP‐CIT was administered after infusion of glucose or placebo (normal saline), and emission data were acquired over 90 minutes in 33 healthy males. For a volume‐of‐interest‐based analysis, an atlas involving sub‐striatal regions of ventral striatum (VST), caudate nucleus and putamen was applied. DAT availability and binding potential (BPND) were measured using a simplified reference tissue method with cerebellum as the reference. Results The glucose‐loaded BPND from the VST negatively correlated with body mass index (BMI), whereas the placebo‐loaded BPND from the VST did not. After loading with glucose, there were substantial increases in BPNDs: 18.3%, 71.7% and 34.0% on average in the VST, caudate nucleus and putamen, respectively. Conclusion Striatal DAT changes after glucose loading, and BMI is associated with glucose‐loaded DAT availability, not with placebo‐loaded DAT availability. DAT might have a role in the reward system of eating behavior.

Dopamine transporter in obesity: a meta-analysis

“…Although DAT has not been discussed widely with regard to obesity, 5 studies of 421 subjects could be included in this study. Except for one study by Chen et al(20), 4 studies have shown no significant association between DAT availability and BMI (1, 21-23). Chen et al used 99m Tc-TRODAT SPECT to measure DAT availability, and showed the negative correlation between DAT availability and BMI (20).…”

“…After reviewing the full text of 10 articles, 5 studies including 421 subjects were eligible for inclusion in this study (1, 20, 22-24) (Figure 1). Two studies with 123 I-FP-CIT (22, 24), one with 99m Tc-TRODAT (20), one with 123 I-PE21 (1), and one with 18 F-FP-CIT (23) were included. DAT availability was extracted from figures in 3 studies (1, 20, 22).…”

“…The calculated DAT availability was downloaded from website of the shared database (Parkinson’s Progression Markers Initiative, PPMI; http://www.ppmi-info.org/) in one study (24). Previously published data from our group was extracted in one study (23). Three studies included the subjects from each institution (1, 20, 23), and the study by van de Giessen et al (22) analyzed the data of European databases of [123I]FP-CIT SPECT scans of healthy controls (ENC-DAT; http://earl.eanm.org/cms/website.php?id=/en/projects/enc-dat.htm) project with 13 sites from 10 European countries without overlaps with PPMI database (24).…”

“…Spline curves of DAT ratio from striatum did not increase or decrease as BMI increases (Figure 4B). As there were 6 subjects with BMI of 25kg/m 2 or more in the study by Pak et al, curve fitting for DAT ratio, and BMI could not be done (23).…”

“…Brain dopamine neurotransmission is regulated by DAT, which drives reuptake of extracellular dopamine into presynaptic neurons (19). Previously, we used the glucose infusion to reflect food intake, and we have discovered that intravenous glucose loading induced substantial increases of striatal DAT availability by the action of insulin (23). From animal studies, insulin acts on striatal insulin receptors to enhance the surface expression of DAT through the PI3 kinase signalling pathway (31, 32).…”