Abstract
Changes in cerebral blood flow (CBF) during a hyperglycemic challenge were mapped, using perfusion-weighted MRI, in a group of non-human primates. Seven female baboons were fasted for 16 h prior to 1-h imaging experiment, performed under general anesthesia, that consisted of a 20-min baseline, followed by a bolus infusion of glucose (500 mg/kg). CBF maps were collected every 7 s and blood glucose and insulin levels were sampled at regular intervals. Blood glucose levels rose from 51.3 ± 10.9 to 203.9 ± 38.9 mg/dL and declined to 133.4 ± 22.0 mg/dL, at the end of the experiment. Regional CBF changes consisted of four clusters: cerebral cortex, thalamus, hypothalamus, and mesencephalon. Increases in the hypothalamic blood flow occurred concurrently with the regulatory response to systemic glucose change, whereas CBF declined for other clusters. The return to baseline of hypothalamic blood flow was observed while CBF was still increasing in other brain regions. The spatial pattern of extra-hypothalamic CBF changes was correlated with the patterns of several cerebral networks including the default mode network. These findings suggest that hypothalamic blood flow response to systemic glucose levels can potentially be explained by regulatory activity. The response of extra-hypothalamic clusters followed a different time course and its spatial pattern resembled that of the default-mode network.
Highlights
Recent evidence suggest that a dysregulation in the central nervous system (CNS)’s control over energy intake, storage, and expenditure contributes to the development of many common metabolic disorders including type 2 diabetes mellitus, insulin resistance, and hyperlipidemia (Jordan et al, 2010)
During the remaining 20 min the glucose, insulin and C-peptide levels returned to typical post-meal values and the WB-cerebral blood flow (CBF) returned to its base-line value (73.2 ± 2.9 mg×100 gm−1×min−1)
Regional pattern of statistically significant CBF change consisted of four regions: cortex, hypothalamus, thalamus, and mesencephalon (Figure 3)
Summary
Recent evidence suggest that a dysregulation in the central nervous system (CNS)’s control over energy intake, storage, and expenditure contributes to the development of many common metabolic disorders including type 2 diabetes mellitus, insulin resistance, and hyperlipidemia (Jordan et al, 2010). It is recognized that small animal models are limited for advancing our understanding of the important neuroregulatory mechanisms that are key drivers of metabolic health in humans (Burcelin, 2010). The contribution of brain insulin signaling to hepatic glucose production in mice and rats differs markedly from its contribution in larger animals and rodent models offer only very limited translational value for studying hepatic glucose production: a key driver of elevated plasma glucose in type 2 diabetes (Burcelin, 2010). A large body-size NHP, such as the baboon, that enables highly controlled and detailed study at the whole body systems level is critical for advancing our understanding of the CNS’s role in metabolic health and disease (Higgins et al, 2016). Advanced brain imaging approaches that are deployable during whole body metabolic studies in this model are lacking
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