Effect of adrenal medullectomy on metabolic responses to chronic intermittent hypoxia in the frequently sampled intravenous glucose tolerance test

Shin, Mi Kyung; Han, Woobum; Joo, Hoon; Bevans‐Fonti, Shannon; Shiota, Masakazu; Stefanovski, Darko; Polotsky, Vsevolod Y.

doi:10.1152/japplphysiol.00975.2016

Cited by 10 publications

(12 citation statements)

References 45 publications

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“…This mechanism is supported by impaired autonomic activity observed in individuals with central hypoventilation syndrome which exhibit sleep disordered breathing, hypoglycemia and hyperinsulinemia ( 134 ). Sympathetic activity is also directly involved in modulating fasting hyperglycemia following exposure to IH ( 135 ), pointing to the ability of the sympathetic system to modulate glucose metabolism in addition to respiratory outcomes ( 133 ). Chronic IH has also been observed to increase tonic and reactive afferent chemoreceptor outputs from the carotid body which in turn effects catecholamine to modulate the autonomic nervous system ( 82 – 84 ) and leads to fasting hyperglycemia ( 136 ) and hypertension ( 84 ).…”

Section: Glycemic Controlmentioning

confidence: 99%

The Bidirectional Relationship Between Obstructive Sleep Apnea and Metabolic Disease

Framnes

Arble

2018

Front. Endocrinol.

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Obstructive sleep apnea (OSA) is a common sleep disorder, effecting 17% of the total population and 40–70% of the obese population (1, 2). Multiple studies have identified OSA as a critical risk factor for the development of obesity, diabetes, and cardiovascular diseases (3–5). Moreover, emerging evidence indicates that metabolic disorders can exacerbate OSA, creating a bidirectional relationship between OSA and metabolic physiology. In this review, we explore the relationship between glycemic control, insulin, and leptin as both contributing factors and products of OSA. We conclude that while insulin and leptin action may contribute to the development of OSA, further research is required to determine the mechanistic actions and relative contributions independent of body weight. In addition to increasing our understanding of the etiology, further research into the physiological mechanisms underlying OSA can lead to the development of improved treatment options for individuals with OSA.

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Section: Glycemic Controlmentioning

confidence: 99%

The Bidirectional Relationship Between Obstructive Sleep Apnea and Metabolic Disease

Framnes

Arble

2018

Front. Endocrinol.

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“…For example, in the study by Polak et al, hepatocytes were cultured in normoxic conditions after isolation for at least 10 h before the measurements of glucose output; In the study by Shin et al, animals were restrained and anaesthetized throughout the measurement procedure. Interestingly, liver PEPCK transcription was no longer affected by 4-week IH exposure when experiments were performed in unrestrained and unanaesthetized mice [31]. Thus, our experiment provides novel insights into the direct impacts of IH on glucose metabolism in isolated liver cells independent of in vivo neural and endocrine regulation.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 79%

Intermittent Hypoxia Disrupts Glucose Homeostasis in Liver Cells in an Insulin-Dependent and Independent Manner

Gu¹,

Yi²,

Feng³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Obstructive sleep apnea is associated with diabetes and insulin resistance, but the underlying mechanisms remain unclear. The purpose of the current study was to determine the molecular effects of intermittent hypoxia (IH) on hepatic insulin signaling and glucose homeostasis, and whether c-Jun NH₂-terminal-kinase (JNK) contributed to metabolic responses to IH in liver cells. Methods: The human HepG₂ cells and rat FAO cells were exposed to 10, 30, 120, 240 or 360 cycles of IH (1% O₂ for 60 s followed by 21% O₂ for 60s, 7.5 cycles per hour) or normoxia as a control. In a subgroup, we exposed cells to 360 cycles of IH with the JNK inhibitor SP600125. After IH exposure, cell glycogen content and glucose output were measured using colorimetric assay kits. Canonical insulin signaling and gluconeogenic genes were measured by western blot and quantitative polymerase chain reaction. Results: IH decreased insulin-stimulated protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) phosphorylation in a time-dependent manner, while inhibiting forkhead box protein O1 (FOXO1) expression and phosphoenolpyruvate carboxykinase (PEPCK) transcription independent of insulin signaling. JNK inhibitor SP600125 partially restored AKT/ GSK-3β phosphorylation and glycogen synthesis, but did not affect other IH-induced glucose metabolic changes. Conclusion: IH in vitro impaired insulin signal transduction in liver cells as assessed by inhibited AKT/GSK-3β phosphorylation via JNK activation. IH inhibited FOXO1 and gluconeogenesis in an insulin-independent manner.

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“…While ADMX is able to reduce blood pressure responses to mineralocorticoids, hypoxia, and some metabolic stressors (Shin et al, 1985; Lange et al, 1998), a similar response was not observed after synthetic GCs exposure. Historically, the adrenal medulla is considered an organ that responds to global stressors (Carter and Goldstein, 2015), but DEX chronic exposure may induce an allostatic load that is not reversible by solely removing the adrenal medulla.…”

Section: Discussionmentioning

confidence: 95%

Dexamethasone Causes Hypertension in Rats Even Under Chemical Blockade of Peripheral Sympathetic Nerves

et al. 2019

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Synthetic glucocorticoids (GCs) are widely used to treat inflammatory conditions. However, chronic use of GCs can lead to hypertension. The cause of this undesired side effect remains unclear. Previously, we developed an in vivo rat model to study the mechanisms underlying hypertension induced by the chronic administration of the potent synthetic GC, dexamethasone (DEX) and found that the catecholamine biosynthetic pathway plays an important role. In the current study, we used this model to investigate the role of the adrenal medulla, renal nerves, and other peripheral sympathetic nerves in DEX-induced hypertension. After 5 days of baseline telemetric recording of mean arterial pressure (MAP) and heart rate (HR), rats were subjected to one of the following treatments: renal denervation (RDNX), adrenal medullectomy (ADMX), 6-hydroxydopamine (6-OHDA, 20 mg/kg, i.p.) to induce chemical sympathectomy, or a combination of ADMX and 6-OHDA. On day 11, the animals received vehicle (VEH) or DEX in drinking water for 7 days, with the latter causing an increase in MAP in control animals. ADMX and RDNX by themselves exacerbated the pressor effect of DEX. In the chemical sympathectomy group, DEX still caused a rise in MAP but the response was lower (ΔMAP of 6-OHDA/DEX < VEH/DEX, p = 0.039). However, when ΔMAP was normalized to day 10, 6-OHDA + DEX did not show any difference from VEH + DEX, certainly not an increase as observed in DEX + ADMX or RDNX groups. This indicates that sympathetic nerves do not modulate the pressor effect of DEX. TH mRNA levels increased in the adrenal medulla in both VEH/DEX (p = 0.009) and 6-OHDA/DEX (p = 0.031) groups. In the 6-OHDA group, DEX also increased plasma levels of norepinephrine (NE) (p = 0.016). Our results suggest that the activation of catecholamine synthetic pathway could be involved in the pressor response to DEX in animals even under chemical sympathectomy with 6-OHDA.

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Effect of adrenal medullectomy on metabolic responses to chronic intermittent hypoxia in the frequently sampled intravenous glucose tolerance test

Cited by 10 publications

References 45 publications

The Bidirectional Relationship Between Obstructive Sleep Apnea and Metabolic Disease

The Bidirectional Relationship Between Obstructive Sleep Apnea and Metabolic Disease

Intermittent Hypoxia Disrupts Glucose Homeostasis in Liver Cells in an Insulin-Dependent and Independent Manner

Dexamethasone Causes Hypertension in Rats Even Under Chemical Blockade of Peripheral Sympathetic Nerves

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