The Glucose Tolerance Test in Mice

Pedro, Patricia Fonseca; Tsakmaki, Anastasia; Bewick, Gavin

doi:10.1007/978-1-0716-0385-7_14

Cited by 20 publications

(26 citation statements)

References 1 publication

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“…Glucose intolerance is a key characteristic of impaired glycaemic control and can be quantified using glucose tolerance tests (GTTs), which are a fundamental tool used in diabetes research 2,23 . GTTs involve measuring baseline blood glucose concentrations before administration of a glucose bolus and subsequent repeated blood glucose measurements for ~2 h typically at 15‐, 30‐, 60‐, 90‐ and 120 min 2,23 . The glucose bolus can be given via several routes, although glucose response varies widely depending on the method chosen as the rate of glucose delivery to the system differs 23 .…”

Section: End Pointsmentioning

confidence: 99%

“…Prior to GTTs, it is common practice to fast mice to eliminate the impact of variability in food intake on glucose homeostasis. Although previous attempts have been made, there remains no standardised fast length with durations commonly ranging from 6 h in the daytime to 16 h overnight 16,17,23 . Furthermore, cages are sometimes changed at the start of fasting to eliminate the risk of food remnants being left in the cage 24,25 .…”

Section: End Pointsmentioning

confidence: 99%

“…Glucose is most commonly administered via i.p. injection but can also be administered orally through gavage or voluntary ingestion of a glucose gel 23 . Insulin is usually administered either via i.p.…”

Section: Experimental Protocolsmentioning

confidence: 99%

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The use of mice in diabetes research: The impact of experimental protocols

et al. 2021

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Mice are used extensively in preclinical diabetes research to model various aspects of blood glucose homeostasis. Careful experimental design is vital for maximising welfare and improving reproducibility of data. Alongside decisions regarding physiological characteristics of the animal cohort (e.g., sex, strain and age), experimental protocols must also be carefully considered. This includes choosing relevant end points of interest and understanding what information they can provide and what their limitations are. Details of experimental protocols must, therefore, be carefully planned during the experimental design stage, especially considering the impact of researcher interventions on preclinical end points. Indeed, in line with the 3Rs of animal research, experiments should be refined where possible to maximise welfare. The role of welfare may be particularly pertinent in preclinical diabetes research as blood glucose concentrations are directly altered by physiological stress responses. Despite the potential impact of variations in experimental protocols, there is distinct lack of standardisation and consistency throughout the literature with regards to several experimental procedures including fasting, cage changing and glucose tolerance test protocol. This review firstly highlights practical considerations with regard to the choice of end points in preclinical diabetes research and the potential for novel technologies such as continuous glucose monitoring and glucose clamping techniques to improve data resolution. The potential influence of differing experimental protocols and in vivo procedures on both welfare and experimental outcomes is then discussed with focus on standardisation, consistency and full disclosure of methods.

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Section: End Pointsmentioning

confidence: 99%

Section: End Pointsmentioning

confidence: 99%

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The use of mice in diabetes research: The impact of experimental protocols

et al. 2021

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“…Oral glucose tolerance tests (OGTTs) are widely used in clinical practice and physiological tests to evaluate normal or impaired glucose metabolism [ 30 ]. In addition, the insulin tolerance test (ITT) is used to investigate insulin action in the whole body by measuring blood glucose levels in response to insulin [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

Anti-Obesity Effects of Combined Cornus officinalis and Ribes fasciculatum Extract in High-Fat Diet-Induced Obese Male Mice

Park

Lee

Jeon

et al. 2021

Animals

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Medicinal plants are widely used as supplements for the treatment of various diseases because of their few side-effects. Here, we examined the anti-obesity effects of a mixture extract of Cornus officinalis and Ribes fasciculatum (CR) in high-fat diet (HFD)-induced obese male mice. Four week old male C57BL/6J mice were fed a normal diet (ND) or 60% high-fat diet (HFD) with different concentrations of CR extracts (75, 150, and 300 mg/kg/day) by oral administration for 12 weeks. CR extract administration prevented HFD-induced weight gain, hepatic steatosis, and adipocyte enlargement through the downregulation of adipogenesis-associated genes in obese male mice. In addition, CR administration improved the impaired glucose metabolism, insulin action, biochemical obesity parameters, and metabolic profiles in HFD-induced male mice. Consequently, the CR extract exhibited beneficial effects on HFD-induced systemic metabolic challenges. Taken together, our findings suggest that CR extract may be a potent therapeutic supplement for the treatment and prevention of obesity.

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“…Indeed, oral gels have been shown to be effective in both the context of GTTs (Cox et al, 2010;Zhang, 2021) and drug delivery (Dhawan et al, 2018;Zhang, 2011). However, there are potential limitations of this method including the need for training, the possibility of non-adherence and the need for mouse separation which could impact welfare (Pedro et al, 2020;Zhang, 2021).…”

Section: Introductionmentioning

confidence: 99%

The glucose tolerance test in mice: sex, drugs and protocol.

Kennard¹,

Nandi²,

Chapple³

et al. 2021

Preprint

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Background and Purpose: Glucose tolerance tests (GTTs) are commonly used in preclinical studies but are poorly standardised. Male mice are often preferred due to more severe phenotypes which may aid in detecting drug effects. Using novel glucose telemetry in undisturbed mice, the effect of different pre-GTT protocols on blood glucose concentrations, GTTs and detection of drug effects were considered. Experimental Approach: Seven male and female C57Bl/6J mice (8-10 weeks) were implanted with HD-XG glucose telemetry devices. Mice were fasted for 16h overnight or 6h in the daytime following a whole cage change, cage change with retention of used bedding or no cage change prior to i.p.GTTs. Glucose tolerance following oral glucose gavage was compared to voluntary ingestion of gels. Using the most refined procedures, 250mg/kg oral metformin and 10nmol/kg i.p. exendin-4 were tested. Key Results: Blood glucose initially increased following cage changing at the start of the fast. For 6h fasting, retaining bedding reduced these initial responses and produced more timely glucose reductions whereas 16h fasts caused pronounced hypoglycaemia. Impaired glucose tolerance in males was exaggerated following 16h fasting or whole cage changes. Refined procedures including voluntarily ingested glucose gels blunted responses but the effects of exendin-4 and metformin were still observable in both sexes. Conclusion and Implications: Variations in GTT protocol can have profound effects on glucose homeostasis. Improved glucose tolerance due to protocol refinement and/or the use of females still allows for detection of drug effects providing evidence that more severe phenotypes are not required when testing drugs.

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The Glucose Tolerance Test in Mice

Cited by 20 publications

References 1 publication

The use of mice in diabetes research: The impact of experimental protocols

The use of mice in diabetes research: The impact of experimental protocols

Anti-Obesity Effects of Combined Cornus officinalis and Ribes fasciculatum Extract in High-Fat Diet-Induced Obese Male Mice

The glucose tolerance test in mice: sex, drugs and protocol.

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