An Afferent Vagal Nerve Pathway Links Hepatic PPARα Activation to Glucocorticoid-Induced Insulin Resistance and Hypertension

Bernal‐Mizrachi, Carlos; Liu, Xiaozhong; Li, Yin; Knutsen, Russell H.; Howard, Michael J.; Arends, J; DeSantis, Pascual; Coleman, Trey; Semenkovich, Clay F.

doi:10.1016/j.cmet.2006.12.010

Cited by 95 publications

(72 citation statements)

References 49 publications

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“…Cutting of the vagus nerve and the effect on insulin release may be compensated by the chronic corticosterone-induced insulin secretion. Bernal-Mizrachi and co-workers showed that dexamethasone-treated rats displayed a disruption of the afferent vagus, glucose intolerance, and hypertension and the vagotomy was able to reverse these effects (Bernal-Mizrachi et al 2007). They consider that glucocorticoid-induced glucose intolerance required intact vagal afferent fibers.…”

Section: Figurementioning

confidence: 99%

“…They consider that glucocorticoid-induced glucose intolerance required intact vagal afferent fibers. Indeed, the complete mechanism of glucocorticoids action in stimulated vagus nerve is still not well understood (Bernal-Mizrachi et al 2007). Although, it is important to highlight that intracerebroventricular (ICV) dexamethasone injections in vagotomized rats did not induce increased food intake, BW, or insulin resistance (Cusin et al 2001).…”

Section: Figurementioning

confidence: 99%

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HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

Miranda

Torrezan

Oliveira

et al. 2016

Journal of Endocrinology

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Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus–pituitary–adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic β-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodiuml-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX–VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX–VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

Miranda

Torrezan

Oliveira

et al. 2016

Journal of Endocrinology

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“…But other studies showed that vagal stimulation may not induce IS, and that afferent hepatic vagal branch activation may contribute to IR. 9 Additional studies suggested that SCI might affect the response to insulin because of alterations in body composition. The combination of higher fat content and reduced skeletal muscle mass, which are frequent in patients with chronic SCI, may result in pronounced competition between free fatty acids and glucose oxidation, leading to IR.…”

Section: Introductionmentioning

confidence: 99%

Insulin resistance in tetraplegia but not in mid-thoracic paraplegia: is the mid-thoracic spinal cord involved in glucose regulation?

et al. 2010

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Study design: Controlled experimental human study. Objectives: To assess insulin resistance (IR) in tetraplegia and paraplegia, and the role of the spinal cord (SC) in glucose regulation. Setting: Laboratory of Spinal Research, Loewenstein Rehabilitation Hospital. Methods: Glucose and insulin levels and the heart rate variation spectral components LF (low frequency), HF (high frequency) and LF/HF were studied at supine rest, head-up tilt and after a standard meal in three groups: 13 healthy subjects, 7 patients with T 4 -T 6 paraplegia and 11 patients with C 4 -C 7 tetraplegia. Results: Glucose and insulin increased significantly after the meal in all groups (Po0.001). Glucose increased significantly more in the tetraplegia than in the other groups (Po0.01). Increases in insulin level tended to accompany increases in LF/HF after the meal in the tetraplegia and control groups but not in the paraplegia group. Conclusion: Post-prandial IR appears in C 4 -C 7 but not in T 4 -T 6 SC injury. The results of the study, combined with previously published findings, are consistent with the hypotheses that IR is related to activation of the sympathetic nervous system, and that below T 4 the mid-thoracic SC is involved in the regulation of glucose and insulin levels.

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“…A c c e p t e d M a n u s c r i p t 8 Interestingly, afferent fibers of the vagus nerve seem to be required for this effect: Selective vagotomy interfered with hepatic PPARα expression and consecutively diminished GCinduced hepatic insulin resistance and hyperglycemia [58,59].…”

Section: Gcs and Hepatic Glucose Metabolismmentioning

confidence: 99%

Glucocorticoids, metabolism and metabolic diseases

Vegiopoulos

Herzig

2007

Molecular and Cellular Endocrinology

440

370

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Since the discovery of the beneficial effects of adrenocortical extracts for treating adrenal insufficiency more than 80 years ago, glucocorticoids (GC) and their cognate, intracellular receptor, the glucocorticoid receptor (GR) have been characterized as critical components of the delicate hormonal control system that determines energy homeostasis in mammals.Whereas physiological levels of GCs are required for proper metabolic control, excessive GC action has been tied to a variety of pandemic metabolic diseases, such as type II diabetes and obesity. Highlighted by its importance for human health, the investigation of molecular mechanisms of GC/GR action has become a major focus in biomedical research. In particular, the understanding of tissue-specific functions of the GC-GR pathway has been proven to be of substantial value for the identification of novel therapeutic options in the treatment of severe metabolic disorders. Therefore, this review focuses on the role of the GC-GR axis for metabolic homeostasis and dysregulation, emphasizing tissue-specific functions of GCs in the control of energy metabolism.

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An Afferent Vagal Nerve Pathway Links Hepatic PPARα Activation to Glucocorticoid-Induced Insulin Resistance and Hypertension

Cited by 95 publications

References 49 publications

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

Insulin resistance in tetraplegia but not in mid-thoracic paraplegia: is the mid-thoracic spinal cord involved in glucose regulation?

Glucocorticoids, metabolism and metabolic diseases

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