Sevoflurane Impairs Insulin Secretion and Tissue‐Specific Glucose Uptake <i>In Vivo</i>

Høyer, Kasper F.; Nielsen, Thomas S.; Risis, Steve; Treebak, Jonas T.; Jessen, Niels

doi:10.1111/bcpt.13087

Cited by 9 publications

(9 citation statements)

References 46 publications

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“…Sevoflurane has extensive regulation effect to tissues by different physiological processes. Previous studies showed that sevoflurane impairs insulin secretion, to induce insulin resistance 51 . Administration of sevoflurane before cardiopulmonary bypass induced cardioprotection in patients undergoing coronary artery bypass graft surgery 52 .…”

Section: Discussionmentioning

confidence: 99%

LncRNA Rik-203 contributes to anesthesia neurotoxicity via microRNA-101a-3p and GSK-3β-mediated neural differentiation

Zhang

Jia

Liu

et al. 2019

Sci Rep

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The mechanism of anesthesia neurotoxicity remains largely to be determined. The effects of long noncoding RNAs (LncRNAs) on neural differentiation and the underlying mechanisms are unknown. We thus identified LncRNA Rik-203 (C130071C03Rik) and studied its role on neural differentiation and its interactions with anesthetic sevoflurane, miRNA and GSK-3β. We found that levels of Rik-203 were higher in hippocampus than other tissues and increased during neural differentiation. Sevoflurane decreased the levels of Rik-203. Rik-203 knockdown reduced mRNA levels of Sox1 and Nestin, the markers of neural progenitor cells, and decreased the count of Sox1 positive cells. RNA-RNA pull-down showed that miR-101a-3p was highly bound to Rik-203. Finally, sevoflurane, knockdown of Rik-203, and miR-101a-3p overexpression all decreased GSK-3β levels. These data suggest that Rik-203 facilitates neural differentiation by inhibiting miR-101a-3p’s ability to reduce GSK-3β levels and that LncRNAs would serve as the mechanism of the anesthesia neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

LncRNA Rik-203 contributes to anesthesia neurotoxicity via microRNA-101a-3p and GSK-3β-mediated neural differentiation

Zhang

Jia

Liu

et al. 2019

Sci Rep

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“…Details of the surgical procedures, the hyperinsulinemic clamp, and the determination of plasma are described elsewhere (Ayala et al 2011, Hoyer et al 2018. One catheter (C20PU-MJV1458; Instech Laboratories, Plymouth Meeting, PA, USA) was placed in the jugular vein and one (C10PU-MCA1459; Instech Laboratories) in carotid artery.…”

Section: Surgical Procedures For Hyperinsulinemic-isoglycemic Clamp Exmentioning

confidence: 99%

“…Anesthesia can have profound effects on the whole-body glucose metabolism (Eger 2004, Kitamura et al 2009. In mice, this is primarily due to impaired glucose uptake in muscle and the central nervous system, whereas hepatic insulin sensitivity remains unaffected (Hoyer et al 2018). Moreover, insulin levels in sevofluraneanesthetized mice is markedly lower, despite high blood glucose levels (Hoyer et al 2018), and this leads to a lower basal hepatic gluconeogenesis.…”

Section: Journal Of Endocrinologymentioning

confidence: 99%

“…In mice, this is primarily due to impaired glucose uptake in muscle and the central nervous system, whereas hepatic insulin sensitivity remains unaffected (Hoyer et al 2018). Moreover, insulin levels in sevofluraneanesthetized mice is markedly lower, despite high blood glucose levels (Hoyer et al 2018), and this leads to a lower basal hepatic gluconeogenesis. This aligns with results from human insulin levels in which pancreatic β-cell secretion is impaired during anesthesia (Tanaka et al 2005).…”

Section: Journal Of Endocrinologymentioning

confidence: 99%

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Assessment of mouse liver [1-13C]pyruvate metabolism by dynamic hyperpolarized MRS

Høyer

Laustsen

Ringgaard

et al. 2019

Journal of Endocrinology

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Hyperpolarized [1-13C]pyruvate magnetic resonance (MR) spectroscopy has the unique ability to detect real-time metabolic changes in vivo owing to its high sensitivity compared with thermal MR and high specificity compared with other metabolic imaging methods. The aim of this study was to explore the potential of hyperpolarized MR spectroscopy for quantification of liver pyruvate metabolism during a hyperinsulinemic–isoglycemic clamp in mice. Hyperpolarized [1-13C]pyruvate was used for in vivo MR spectroscopy of liver pyruvate metabolism in mice. Mice were divided into two groups: (i) non-stimulated 5-h fasted mice and (ii) hyperinsulinemic-isoglycemic clamped mice. During clamp conditions, insulin and donor blood were administered at a constant rate, whereas glucose was infused to maintain isoglycemia. When steady state was reached, insulin-stimulated mice were rapidly infused with hyperpolarized [1-13C]pyruvate for real-time tracking of the dynamic distribution of metabolic derivatives from pyruvate, such as [1-13C]lactate, [1-13C]alanine and [13C]bicarbonate. Isotopomer analysis of plasma glucose confirmed 13C-incorporation from [1-13C]pyruvate into glucose was increased in fasted mice compared with insulin-stimulated mice, demonstrating an increased gluconeogenesis in fasted mice. The AUC ratios for [1-13C]alanine/[1-13C]pyruvate (38.2%), [1-13C]lactate/[1-13C]pyruvate (41.8%) and [13C]bicarbonate/[1-13C]pyruvate (169%) all increased significantly during insulin stimulation. Hyperpolarized [1-13C]pyruvate can be used for in vivo MR spectroscopy of liver pyruvate metabolism during hyperinsulinemic-isoglycemic clamp conditions. Under these conditions, insulin decreased gluconeogenesis and increased [1-13C]alanine, [1-13C]lactate and [13C]bicarbonate after a [1-13C]pyruvate bolus. This application of in vivo spectroscopy has the potential to identify impairments in specific metabolic pathways in the liver associated with obesity, insulin resistance and nonalcoholic fatty liver disease.

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“…For patients in the intensive care unit (ICU), the prevalence of hyperglycemia (>180 mg/dl) is 32.2% because of decreased responsiveness to the metabolic actions of insulin, named insulin resistance [ 1 , 2 ]. Volatile anesthetics, in particular halothane, isoflurane, and sevoflurane, cause impaired glucose tolerance, insulin resistance, and hyperglycemia, suggesting active roles in surgery- and critically ill-accompanied hyperglycemia [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Propofol Improved Glucose Tolerance Associated with Increased FGF-21 and GLP-1 Production in Male Sprague-Dawley Rats

Hung

Wang

et al. 2020

Molecules

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Anesthetics, particularly volatile anesthetics, have been shown to impair glucose metabolism and cause hyperglycemia, closely linking them with mortality and morbidity as related to surgery. Beyond being an anesthetic used for general anesthesia and sedation, intravenous hypnotic propofol displays an effect on glucose metabolism. To extend the scope of propofol studies, its effects on glucose metabolism were evaluated in male Sprague-Dawley rats of various ages. Unlike chloral hydrate and isoflurane, propofol had little effect on basal glucose levels in rats at 2 months of age, although it did reduce chloral hydrate- and isoflurane-induced hyperglycemia. Propofol reduced postload glucose levels after either intraperitoneal or oral administration of glucose in both 7- and 12-month-old rats, but not those at 2 months of age. These improved effects regarding propofol on glucose metabolism were accompanied by an increase in insulin, fibroblast growth factor-21 (FGF-21), and glucagon-like peptide-1 (GLP-1) secretion. Additionally, an increase in hepatic FGF-21 expression, GLP-1 signaling, and FGF-21 signaling, along with a decrease in endoplasmic reticulum (ER) stress, were noted in propofol-treated rats at 7 months of age. Current findings imply that propofol may turn into insulin-sensitizing molecules during situations of existing insulin resistance, which involve FGF-21, GLP-1, and ER stress.

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Sevoflurane Impairs Insulin Secretion and Tissue‐Specific Glucose Uptake In Vivo

Cited by 9 publications

References 46 publications

LncRNA Rik-203 contributes to anesthesia neurotoxicity via microRNA-101a-3p and GSK-3β-mediated neural differentiation

LncRNA Rik-203 contributes to anesthesia neurotoxicity via microRNA-101a-3p and GSK-3β-mediated neural differentiation

Assessment of mouse liver [1-13C]pyruvate metabolism by dynamic hyperpolarized MRS

Propofol Improved Glucose Tolerance Associated with Increased FGF-21 and GLP-1 Production in Male Sprague-Dawley Rats

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