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      In vivo techniques for assessment of insulin sensitivity and glucose metabolism

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          Abstract

          Metabolic tests are vital to determine in vivo insulin sensitivity and glucose metabolism in preclinical models, usually rodents. Such tests include glucose tolerance tests, insulin tolerance tests, and glucose clamps. Although these tests are not standardized, there are general guidelines for their completion and analysis that are constantly being refined. In this review, we describe metabolic tests in rodents as well as factors to consider when designing and performing these tests.

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          Most cited references106

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          Diagnosis and Classification of Diabetes Mellitus

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            Glucose clamp technique: a method for quantifying insulin secretion and resistance.

            Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.
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              Olfactory exposure to males, including men, causes stress and related analgesia in rodents.

              We found that exposure of mice and rats to male but not female experimenters produces pain inhibition. Male-related stimuli induced a robust physiological stress response that results in stress-induced analgesia. This effect could be replicated with T-shirts worn by men, bedding material from gonadally intact and unfamiliar male mammals, and presentation of compounds secreted from the human axilla. Experimenter sex can thus affect apparent baseline responses in behavioral testing.

                Author and article information

                Journal
                J Endocrinol
                J Endocrinol
                JOE
                The Journal of Endocrinology
                Bioscientifica Ltd (Bristol )
                0022-0795
                1479-6805
                31 January 2024
                10 January 2024
                01 March 2024
                : 260
                : 3
                : e230308
                Affiliations
                [1 ]Centre for Addiction and Mental Health , Toronto, Ontario, Canada
                [2 ]Institute of Medical Sciences , University of Toronto, Toronto, Ontario, Canada
                [3 ]Department of Pharmacology , University of Toronto, Toronto, Ontario, Canada
                [4 ]Department of Psychiatry , University of Toronto, Toronto, Ontario, Canada
                [5 ]Banting & Best Diabetes Centre , Toronto, Ontario, Canada
                [6 ]Department of Physiology , University of Toronto, Toronto, Ontario, Canada
                Author notes
                Correspondence should be addressed to S Pereira: sandra.pereira@ 123456camh.ca

                This paper forms part of a themed collection on Insulin Resistance and Type 2 Diabetes Mellitus. The Guest Editors for this collection were Matthias Blüher, Stefan Bornstein and Martin Haluzík.

                Author information
                http://orcid.org/0000-0002-9223-4984
                Article
                JOE-23-0308
                10.1530/JOE-23-0308
                10895285
                38198372
                b60f07c0-ae31-4f00-a050-577f32e1d951
                © the author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 23 September 2023
                : 10 January 2024
                Funding
                Funded by: BD, doi http://dx.doi.org/10.13039/100017412;
                Funded by: Canadian Institutes of Health Research, doi http://dx.doi.org/10.13039/501100000024;
                Funded by: Department of Psychiatry, University of Toronto, doi http://dx.doi.org/10.13039/100015070;
                Categories
                Thematic Review

                Endocrinology & Diabetes
                whole animal physiology,glucose metabolism,insulin sensitivity,glucose tolerance

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