Abstract

Evaluation of the impact of anesthesia on oral glucose tolerance in mice. Anesthesia is often used when performing OGTT in mice to avoid the stress of gavage and blood sampling, although anesthesia may influence gastrointestinal motility, blood glucose, and plasma insulin dynamics. C57Bl/6 mice were anesthetized using the following commonly used regimens: (1) hypnorm/midazolam repetitive or single injection; (2) ketamine/xylazine; (3) isoflurane; (4) pentobarbital; and (5) A saline injected, nonanesthetized group. Oral glucose was administered at time 0 min and blood glucose measured in the time frame −15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine/xylazine lowered insulin responses and resulted in severe hyperglycemia throughout the experiment; (3) isoflurane did not only alter the insulin secretion but also resulted in severe hyperglycemia; (4) pentobarbital resulted in both increased insulin secretion and impaired glucose tolerance. All four anesthetic regimens altered the oral glucose tolerance, and we conclude that anesthesia should not be used when performing metabolic studies in mice.

Highlights

  • The oral glucose tolerance test (OGTT) is a widely used experimental procedure for metabolic studies in mice

  • Not including oral glucose tolerance tests, have shown that: (1) the hypnorm/midazolam combination (Hyp/Mid) causes little alteration in blood glucose (BG) or insulin (Zuurbier et al 2014), whereas great increases in both BG and insulin may be seen after administration of only hypnorm (Johansen et al 1994); (2) the ketamine/ xylazine combination (Ket/Xyl) increases BG and inhibits a 2016 The Authors

  • Hypnorm/midazolam (Hyp/Mid) combination was applied as repetitive injections (Hyp/Mid Rep) or as a single injection at time À15 min (Hyp/Mid Single)

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Summary

Introduction

The oral glucose tolerance test (OGTT) is a widely used experimental procedure for metabolic studies in mice. The NIH mouse Metabolic Phenotyping Center Consortium has provided a standard operating procedure for performing glucose tests in mice (Ayala et al 2010), most studies differ significantly with respect to parameters such as anesthesia, fasting time, glucose dose, gavage material, time points for blood glucose (BG) measurements, and time points for blood sampling for hormonal analysis.

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