Suprachiasmatic Nucleus Neuropeptides and Their Control of Endogenous Glucose Production

Foppen, Ewout; Tan, A.; Ackermans, M. T.; Fliers, Eric; Kalsbeek, Andries

doi:10.1111/jne.12365

Cited by 15 publications

(13 citation statements)

References 123 publications

(180 reference statements)

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“…Since, in agreement with other studies (36), the time courses of the counterregulatory hormones ACTH and cortisol were comparable between conditions, it is unlikely that they were involved in the mediation of oxytocin's effects on glucose tolerance, although a link between hypothalamicpituitary-adrenal (HPA) axis activity and glucose homeostasis clearly exists. We have previously observed a dampening influence of oxytocin on HPA axis activity under basal conditions (5), but this effect appears to be even more pronounced in response to social and physical stress (37,38).…”

Section: Discussionsupporting

confidence: 88%

Oxytocin Improves β-Cell Responsivity and Glucose Tolerance in Healthy Men

et al. 2016

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In addition to its pivotal role in psychosocial behavior, the hypothalamic neuropeptide oxytocin contributes to metabolic control by suppressing eating behavior. Its involvement in glucose homeostasis is less clear, although pilot experiments suggest that oxytocin improves glucose homeostasis. We assessed the effect of intranasal oxytocin (24 IU) administered to 29 healthy, fasted male subjects on glucose homeostasis measured by means of an oral glucose tolerance test. Parameters of glucose metabolism were analyzed according to the oral minimal model. Oxytocin attenuated the peak excursion of plasma glucose and augmented the early increases in insulin and C-peptide concentrations in response to the glucose challenge, while slightly blunting insulin and C-peptide peaks. Oral minimal model analyses revealed that oxytocin compared with placebo induced a pronounced increase in β-cell responsivity (PHI) that was largely due to an enhanced dynamic response (PHI), and a more than twofold improvement in glucose tolerance (disposition index). Adrenocorticotropic hormone (ACTH), cortisol, glucagon, and nonesterified fatty acid (NEFA) concentrations were not or were only marginally affected. These results indicate that oxytocin plays a significant role in the acute regulation of glucose metabolism in healthy humans and render the oxytocin system a potential target of antidiabetic treatment.

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Section: Discussionsupporting

confidence: 88%

Oxytocin Improves β-Cell Responsivity and Glucose Tolerance in Healthy Men

et al. 2016

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“…Silencing neuronal firing by tetrodotoxin administration at the SCN, but not the PVN, elevated blood glucose levels (Kalsbeek et al, 2004). Consistent with this finding, tetrodotoxin administration at the SCN, but not at the PVN, increased EGP in the glucose clamp analysis (Foppen et al, 2016). Considering the direct projection from the SCN to the PVN and the high basal blood glucose levels in anti-phase with the SCN neuronal firing activity in rats, these findings support a role of the SCN-PVN-SNS-EGP signaling in governing the rhythmic blood glucose levels under the normal physiological condition.…”

Section: Evidence Supporting a Role Of Central Clock In Energy Metabosupporting

confidence: 60%

Central Circadian Clock Regulates Energy Metabolism

Ding¹,

Gong²,

Eckel‐Mahan³

et al. 2018

Advances in Experimental Medicine and Biology

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Our body not only responds to environmental changes but also anticipates them. The light and dark cycle with the period of about 24 hours is a recurring environmental change that determines the diurnal variation in food availability and safety from predators in nature. As a result, the circadian clock is evolved in most animals to align locomotor behaviors and energy metabolism with the light cue. The central circadian clock in mammals is located at the suprachiasmatic nucleus (SCN) of the hypothalamus in the brain. We here review the molecular and anatomic architecture of the central circadian clock in mammals; describe the experimental and observational evidence that suggests a critical role of the central circadian clock in shaping systemic energy metabolism; and discuss the involvement of endocrine factors, neuropeptides, and the autonomic nervous system in the metabolic functions of the central circadian clock.

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“…Projections from the paraventricular hypothalamic nuclei (PVN) to the nucleus of solitary tract and rostral ventrolateral medulla (RVLM) constitutes the pre-autonomic sympathetic system which in turn projects to the intermediolateral grey column to reach the cardiac sympathetic plexus (Affleck et al 2012;Pyner 2014). This circuit has also been implicated in the neural control of metabolism, electrolyte and fluid balance through the regulation of neuropeptides, such as angiotensin II, orexin, and adiponectin, and neurotransmitters involved in hypothalamic-hypophysial homeostatic regulation (Eliava et al 2016;Foppen et al 2016;Hao et al 2016).…”

mentioning

confidence: 99%

Age‐dependent alterations to paraventricular nucleus insulin‐like growth factor 1 receptor as a possible link between sympathoexcitation and inflammation

Ogundele

Lee

Francis

2016

Journal of Neurochemistry

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Modifications to neural circuits of the paraventricular hypothalamic nucleus (PVN) have been implicated in sympathoexcitation and systemic cardiovascular dysfunction. However, to date, the role of insulin-like growth factor 1 receptor (IGF-1R) expression on PVN pathophysiology is unknown. Using confocal immunofluorescence quantification and electrophysiological recordings from acute PVN slices, we investigated the mechanism through which age-dependent IGF-1R depletion contributes to the progression of inflammation and sympathoexcitation in the PVN of spontaneously hypertensive rats (SHR). Four and twenty weeks old SHR and Wistar Kyoto (WKY) rats were used for this study. Our data showed that Angiotensin I/II and pro-inflammatory high mobility box group protein 1 (HMGB1) exhibited increased expression in the PVN of SHR versus WKY at 4 weeks (p<0.01), and were even more highly expressed with age in SHR (p<0.001). This correlated with a significant decrease in IGF-1R expression, with age, in the PVN of SHR when compared with WKY (p<0.001) and were accompanied by related changes in astrocytes and microglia. In subsequent analyses, we found an age-dependent change in the expression of proteins associated with IGF-1R signaling pathways involved in inflammatory responses and synaptic function in the PVN. MAPK/ErK was more highly expressed in the PVN of SHR by the 4th week (p<0.001; vs WKY), while expression of neuronal nitric oxide synthase (nNOS; p<0.001) and calcium-calmodulin dependent kinase II alpha (CamKIIα; p<0.001) were significantly decreased by the 4th and 20th week respectively. Age-dependent changes in MAPK/ErK expression in the PVN correlated with an increase in the expression of vesicular glutamate transporter (VGLUT2) (p<0.001 vs WKY), while decreased levels of CamKIIα was associated with a decreased expression of tyrosine hydroxylase (p<0.001) by the 20th week. In addition, reduced labeling for GABA in the PVN of SHR (p<0.001) correlated with a decrease in nNOS labeling (p<0.001) when compared with the WKY by the 20th week. Electrophysiological recordings from neurons in acute slice preparations of the PVN of 4 weeks old SHR revealed spontaneous post-synaptic currents of higher frequency when compared with neurons from WKY PNV slices of the same age (p<0.001; n=14 cells). This also correlated with an increase in post-synaptic densities (PSD-95) in the PVN of SHR when compared with the WKY (p<0.001). Overall, we found an age-dependent reduction of IGF-1R, and related altered expression of associated downstream signaling molecules that may represent a link between the concurrent progression of synaptic dysfunction and inflammation in the PVN of SHR.

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Suprachiasmatic Nucleus Neuropeptides and Their Control of Endogenous Glucose Production

Cited by 15 publications

References 123 publications

Oxytocin Improves β-Cell Responsivity and Glucose Tolerance in Healthy Men

Oxytocin Improves β-Cell Responsivity and Glucose Tolerance in Healthy Men

Central Circadian Clock Regulates Energy Metabolism

Age‐dependent alterations to paraventricular nucleus insulin‐like growth factor 1 receptor as a possible link between sympathoexcitation and inflammation

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