Brief communication: β-cell function influences dopamine receptor availability

Abstract

We aim to identify physiologic regulators of dopamine (DA) signaling in obesity but previously did not find a compelling relationship with insulin sensitivity measured by oral-minimal model (OMM) and DA subtype 2 and 3 receptor (D2/3R) binding potential (BP ND ). Reduced disposition index (DI), a β-cell function metric that can also be calculated by OMM, was shown to predict a negative reward behavior that occurs in states of lower endogenous DA. We hypothesized that reduced DI would occur with higher D2/3R BP ND , reflecting lower endogenous DA. Participants completed PET scanning, with a displaceable radioligand to measure D2/3R BP ND , and a 5-hour oral glucose tolerance test to measure DI by OMM. We studied 26 age-similar females without (n = 8) and with obesity (n = 18) (22 vs 39 kg/m 2 ). Reduced DI predicted increased striatal D2/3R BP ND independent of BMI. By accounting for β-cell function, we were able to determine that the state of insulin and glucose metabolism is pertinent to striatal D2/3R BP ND in obesity. Clinical Trial Registration Number : NCT00802204

Central nervous pathways of insulin action in the control of metabolism and food intake

“…Evidence is accumulating that the connection between central and peripheral insulin and glucose metabolism may depend on dopamine function. Obesity is associated with a dysfunctional brain dopamine system 109 and reduced peripheral insulin sensitivity as well as beta cell function are related to low dopamine levels in the brain 110,111 . The central insulin-dopamine interaction seems to contribute to these findings.…”

Molecular Imaging of Central Dopamine in Obesity: A Qualitative Review across Substrates and Radiotracers

“…The dopamine system is, of course, an integral part of the brain and the body as a whole. Of note in this context is that dopamine interacts with other neurotransmitter systems that have also been associated with obesity, such as the serotonin (reviewed in [23,55,58,59]) and opiate system [37,38,83], as well as with the neuroendocrine hormone insulin [43,[84][85][86][87][88]. PET and SPECT studies targeting multiple neurotransmitter systems in the same sample may provide clearer answers in this regard.…”

Dorsal striatal response to taste is modified by obesity and insulin resistance

“…Although much of this data has been in rodent models, stimulatory effects of insulin on cerebrocortical activity, assessed by magnetoencephalography [8], and on glucose metabolism in brain regions pertinent to appetite and reward, assessed by using 18‐F fluorodeoxyglucose positron emission tomography [9], are attenuated in people with obesity and insulin resistance compared with lean and insulin sensitive control individuals. We have previously shown that dopamine binding to dopamine type 2 receptors in the fasting state is negatively associated with insulin sensitivity and positively associated with fasting insulin concentration and body mass index (BMI) [10, 11]. The current work aimed to expound on these findings by investigating whether hyperinsulinemia and insulin resistance alter neural responses to taste in people with obesity.…”