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Evaluating The Glucose Tolerance Test In Mice

Ipgtt

Ipgtt

An oral glucose tolerance test (OGTT) or intra-peritoneal glucose tolerance test (IPGTT) is used to assess the bodys ability to metabolize glucose. In humans an OGTT is commonly used to diagnose type 2 diabetes. In animal research the GTT is used to assess the degree of diabetes and also to test the desired effects of insulin or other drugs on the bodys ability to process glucose. It can also be used to detect the unintended side-effects of drugs intended to treat other unrelated diseases. Figure 1: Oral glucose tolerance test in two groups of n=3 rats. The blue line represents the diabetic group and the red line represents the normal group. The periodic points represent test strip samples. Figure 2: Intraperitoneal glucose tolerance test in two groups of n=3 rats. The blue line represents the diabetic group and the red line represents the normal group. The periodic points represent test strip samples. Traditional methods of glucose tolerance tests consist of the following basic steps: Fast the subject for 6-16 hours, depending on the protocol and IACUC considerations. Calculate the desired glucose dose based on the animals weight. Typical oral dose of 2-5 mg/kg or IP dose of 2 mg/kg. Collect a baseline (predose) blood glucose reading. Collect blood glucose data at multiple points along the curve. For an OGTT this might include points at 5, 15, 30, 60, 120, 180 minutes post-dose. An IPGTT might include an additional point at 10 minutes and omission of the 180 minute point. Relevant Parameters from this test include Peak Glucose, Time to Peak, Area Under Curve, Return to Baseline, Glucose at time X Implantable telemetry will automate this data collection with no need to collect manual measurements other than for (optional) reference purposes. Continuous data will provid Continue reading >>

Melior Discovery: Insulin Tolerance Test

Melior Discovery: Insulin Tolerance Test

The Insulin Tolerance Test (ITT) is designed to determine the sensitivity of insulin receptors in tissue by measuring blood glucose levels before and after insulin administration.This is a standard test to determine the diabetic status in humans and experimental animals. This test is used to assess the efficacy of insulin-like compounds and pharmacological agents that can modify insulin responsiveness. The graph above illustrates the difference in response to an insulin challenge (ITT) in insulin-depleted (streptozotocin-treated) mice administered insulin, insulin+MLR-1023 or MLR-1023 alone. This study shows that MLR-1023 significantly extended the duration and magnitude of the insulin response. Data are mean SEM, *p<0.05, ***p<0.001 compared to vehicle. MLR-1023 is a potential "next-generation" insulin sensitizer that works independently of a PPAR mechanism. This compound improves glycemic control by directly and selectively activating the enzyme Lyn kinase. Lyn kinase has been previously shown to modulate the insulin-signaling pathway. MLR-1023 is the first described specific and direct activator of Lyn kinase that elicits glycemic control activity through potentiation of insulin activity. For more information on MLR-1023, please visitour sister site, Melior Pharmaceuticals . In addition to MLR-1023 studies, Melior routinely performs ITT studies in mice fed a "Western diet" that is designed to approximate the "typical" human diet of North Americaand Europe. The "Western diet" contains greater than five times more fat than the normal diet. In this study, mice were fasted four hours prior to study commencement. Insulin tolerance test. A baseline glucose measurement was evaluated one hour prior to dosing. At time 0 minutes, mice received either insulin or vehicle (no in Continue reading >>

Jlr : Journal Of Lipid Research

Jlr : Journal Of Lipid Research

*Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands Netherlands Organization for Applied Scientific Research (TNO) Prevention and Health, Gaubius Laboratory, Leiden, The Netherlands Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands 1To whom correspondence should be addressed. e-mail: [email protected] Fasting readily induces hepatic steatosis. Hepatic steatosis is associated with hepatic insulin resistance. The purpose of the present study was to document the effects of 16 h of fasting in wild-type mice on insulin sensitivity in liver and skeletal muscle in relation to 1) tissue accumulation of triglycerides (TGs) and 2) changes in mRNA expression of metabolically relevant genes. Sixteen hours of fasting did not show an effect on hepatic insulin sensitivity in terms of glucose production in the presence of increased hepatic TG content. In muscle, however, fasting resulted in increased insulin sensitivity, with increased muscle glucose uptake without changes in muscle TG content. In liver, fasting resulted in increased mRNA expression of genes promoting gluconeogenesis and TG synthesis but in decreased mRNA expression of genes involved in glycogenolysis and fatty acid synthesis. In muscle, increased mRNA expression of genes promoting glucose uptake, as well as lipogenesis and -oxidation, was found. In conclusion, 16 h of fasting does not induce hepatic insulin resistance, although it causes liver steatosis, whereas muscle insulin sensitivity increases without changes in muscle TG content. Therefore, fasting induces differential changes in tissue-specific insulin sensitivity, and liver and muscle TG contents are unlikely to be involved in these changes. Published, JLR Papers i Continue reading >>

Evaluating The Glucose Tolerance Test In Mice.

Evaluating The Glucose Tolerance Test In Mice.

Evaluating the glucose tolerance test in mice. Andrikopoulos S, et al. Am J Physiol Endocrinol Metab. 2008. Univ. of Melbourne, Dept. of Medicine, Heidelberg Heights, Victoria, Australia. [email protected] Am J Physiol Endocrinol Metab. 2008 Dec;295(6):E1323-32. doi: 10.1152/ajpendo.90617.2008. Epub 2008 Sep 23. The objective of this study was to determine the optimal conditions under which to assess glucose tolerance in chow- and high-fat-fed C57BL/6J mice. Mice were fed either chow or high-fat diet for 8 wk. Variables tested were fasting duration (0-, 3-, 6-, and 24-h and overnight fasting), route of administration (intraperitoneal vs. oral) load of glucose given (2, 1, or 0.5 g/kg and fixed 50-mg dose), and state of consciousness. Basal glucose concentrations were increased in high-fat- compared with chow-fed mice following 6 h of fasting (9.1 +/- 0.3 vs. 7.9 +/- 0.4 mmol/l P = 0.01). Glucose tolerance was most different and therefore significant (P = 0.001) in high-fat-fed mice after 6 h of fasting (1,973 +/- 96 vs. 1,248 +/- 83 mmol.l(-1).120 min(-1)). The difference in glucose tolerance was greater following an OGTT (142%), in contrast to an IPGTT, with a 127% difference between high fat and chow. We also found that administering 2 g/kg of glucose resulted in a greater level of significance (P = 0.0008) in glucose intolerance in high-fat- compared with chow-fed mice. A fixed dose of 50 mg glucose regardless of body weight was enough to show glucose intolerance in high-fat- vs. chow-fed mice. Finally, high-fat-fed mice showed glucose intolerance compared with their chow-fed counterparts whether they were tested under conscious or anesthetized conditions. We conclude that 2 g/kg glucose administered orally following 6 h of fasting is best to assess glucose toleran Continue reading >>

Ajs1669, A Novel Small-molecule Muscle Glycogen Synthase Activator, Improves Glucose Metabolism And Reduces Body Fat Mass In Mice

Ajs1669, A Novel Small-molecule Muscle Glycogen Synthase Activator, Improves Glucose Metabolism And Reduces Body Fat Mass In Mice

AJS1669, a novel small-molecule muscle glycogen synthase activator, improves glucose metabolism and reduces body fat mass in mice Affiliations: Innovation Promotion Department, Research Institute, EA Pharma Co., Ltd., Kawasaki, Kanagawa 210-868, Japan, Nutrition and Health Science Group Frontier Research Laboratories, Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Kanagawa 210-8681, Japan, Business Development Department, EA Pharma Co., Ltd., Chuo-ku, Tokyo 104-0042, Japan, Novel Projects Research Group, Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Kanagawa 210-8681, Japan, Intellectual Property Department, EA Pharma Co., Ltd., Chuo-ku, Tokyo 104-0042, Japan Published online on: March 7, 2017 Copyright: Nakano et al. This is an open access article distributed under the terms of Creative Commons Attribution License. Metrics: HTML 0 views | PDF 0 views Cited By (CrossRef): 0 citations Impaired glycogen synthesis and turnover are common in insulin resistance and type 2 diabetes. As glycogen synthase (GS) is a key enzyme involved in the synthetic process, it presents a promising therapeutic target for the treatment of type2 diabetes. In the present study, we identified a novel, potent and orally available GS activator AJS1669 {sodium 2-[[5-[[4-(4,5-difluoro-2-methylsulfanyl-phenyl)phenoxy] methyl]furan-2-carbonyl]-(2-furylmethyl)amino] acetate}. Invitro, we performed a glycogen synthase1(GYS1) activation assay for screening GS activators and identified that the activity of AJS1669 was further potentiated in the presence of glucose-6-phosphate (G6P). Invivo, we used ob/ob mice to evaluate the novel anti-diabetic effects of AJS1669 by measuring basal blood glucose levels, glucose tolerance and body fat mass index. Repeated administration of AJS1669 over Continue reading >>

Evaluating The Glucose Tolerance Test In Mice

Evaluating The Glucose Tolerance Test In Mice

Evaluating the glucose tolerance test in mice The objective of this study was to determine the optimal conditions under which to assess glucose tolerance in chow- and high-fat-fed C57BL/6J mice. Mice were fed either chow or high-fat diet for 8 wk. Variables tested were fasting duration (0-, 3-, 6-, and 24-h and overnight fasting), route of administration (intraperitoneal vs. oral) load of glucose given (2, 1, or 0.5 g/kg and fixed 50-mg dose), and state of consciousness. Basal glucose concentrations were increased in high-fat- compared with chow-fed mice following 6 h of fasting (9.1 +/- 0.3 vs. 7.9 +/- 0.4 mmol/l P = 0.01). Glucose tolerance was most different and therefore significant (P = 0.001) in high-fat-fed mice after 6 h of fasting (1,973 +/- 96 vs. 1,248 +/- 83 mmol.l(-1).120 min(-1)). The difference in glucose tolerance was greater following an OGTT (142%), in contrast to an IPGTT, with a 127% difference between high fat and chow. We also found that administering 2 g/kg of glucose resulted in a greater level of significance (P = 0.0008) in glucose intolerance in high-fat- compared with chow-fed mice. A fixed dose of 50 mg glucose regardless of body weight was enough to show glucose intolerance in high-fat- vs. chow-fed mice. Finally, high-fat-fed mice showed glucose intolerance compared with their chow-fed counterparts whether they were tested under conscious or anesthetized conditions. We conclude that 2 g/kg glucose administered orally following 6 h of fasting is best to assess glucose tolerance in mice under these conditions. 2018 Digital Science & Research Solutions, Inc. All Rights Reserved | About us Privacy policy Legal terms VPAT Citation Count is the number of times that this paper has been cited by other published papers in the database. The Altmetr Continue reading >>

Validation Of Homa-ir In A Model Of Insulin-resistance Induced By A High-fat Diet In Wistar Rats

Validation Of Homa-ir In A Model Of Insulin-resistance Induced By A High-fat Diet In Wistar Rats

Validation of HOMA-IR in a model of insulin-resistance induced by a high-fat diet in Wistar rats 1Programa de Ps-Graduao em Medicina, Cincias Mdicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil 2Grupo para o Estudo da Resistncia Insulina (GERI), Porto Alegre, RS, Brasil 3Curso de Nutrio, Departamento de Medicina Interna, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil 4Servio de Medicina Interna, Hospital de Clnicas de Porto Alegre (HCPA), Porto Alegre, RS, Brasil The present study aimed to validate homeostasis model assessment of insulin resistance (HOMA-IR) in relation to the insulin tolerance test (ITT) in a model of insulin-resistance in Wistar rats induced by a 19-week high-fat diet. A total of 30 male Wistar rats weighing 200-300 g were allocated into a high-fat diet group (HFD) (55% fat-enriched chow, ad lib, n = 15) and a standard-diet group (CD) standard chow, ad lib, n = 15), for 19 weeks. ITT was determined at baseline and in the 19th week. HOMA-IR was determined between the 18-19th week in three different days and the mean was considered for analysis. Area under the curve (AUC-ITT) of the blood glucose excursion along 120 minutes after intra-peritoneal insulin injection was determined and correlated with the corresponding fasting values for HOMA-IR. AUC-ITT and HOMA-IR were significantly greater after 19th week in HFD compared to CD (p < 0.001 for both). AUC-OGTT was also higher in HFD rats (p = 0.003). HOMA-IR was strongly correlated (Pearsons) with AUC-ITT r = 0.637; p < 0.0001. ROC curves of HOMA-IR and AUC-ITT showed similar sensitivity and specificity. HOMA-IR is a valid measure to determine insulin-resistance in Wistar rats. Arch Endocrinol Metab. Continue reading >>

Use Of Anesthesia Dramatically Alters The Oral Glucose Tolerance And Insulin Secretion In C57bl/6 Mice

Use Of Anesthesia Dramatically Alters The Oral Glucose Tolerance And Insulin Secretion In C57bl/6 Mice

Author information Article notes Copyright and License information Received 2016 March 14; Revised 2016 May 11; Accepted 2016 May 13. Copyright 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. 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 0min and blood glucose measured in the time frame 15 to +150min. Plasma insulin concentration was measured at time 0 and 20min. 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 Continue reading >>

Metabolic Phenotyping Guidelines: Assessing Glucose Homeostasis In Rodent Models

Metabolic Phenotyping Guidelines: Assessing Glucose Homeostasis In Rodent Models

Introduction The incidence of diabetes mellitus, particularly obesity-related type 2 diabetes, is increasing at an alarming rate in the developed world, and this epidemic is driving numerous research programmes into the causes of, and new treatment regimens for, this metabolic disorder. The complex hormonal control of nutrient homeostasis involves numerous tissues and organs, including liver, skeletal muscle, adipose, endocrine pancreas and CNS. While in vitro studies can provide cellular mechanistic insights, it is inevitable that in vivo models are needed to study the integrated control systems. Many animal models for the study of diabetes already exist, with various mechanisms for inducing either type 1 or type 2 diabetes (King 2012). Furthermore, genetically modified mouse models in which genes are up- or down-regulated either globally or in a tissue-specific manner are increasingly used to assess the physiological role of a potential target in glucose homeostasis and the development of diabetes. Consequently, techniques for accurately assessing glucose homeostasis in vivo in rodents are essential tools in current diabetes research. Mice and rats are by far the two most commonly used species for experimental studies of glucose homeostasis, and both models have specific advantages and disadvantages. The primary advantage of using a rat model is a technical consideration in that the larger size of the rat facilitates complex surgical procedures such as catheterisation, and the larger blood volume allows the sampling of more frequent and/or larger blood samples to enable detailed and simultaneous monitoring of multiple plasma hormone levels. Surgical techniques developed in the rat have been successfully miniaturised for use in mouse models, although they are technical Continue reading >>

Frontiers | Individual Variation In Conditional Cell Ablation Mice Contributes Significant Biases In Evaluating Cell Functional Recovery | Endocrinology

Frontiers | Individual Variation In Conditional Cell Ablation Mice Contributes Significant Biases In Evaluating Cell Functional Recovery | Endocrinology

Front. Endocrinol., 14 September 2017 | Individual Variation in Conditional Cell Ablation Mice Contributes Significant Biases in Evaluating Cell Functional Recovery 1Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong 2Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong Despite the DTA (Ins2-rtTA; Tet-DTA) mice have been developed as a valuable tool to study cell regeneration, their individual variation in therapeutic efficacy has not been characterized. Here, we demonstrated that the DTA mice exhibited significant variations in both spontaneous and acquired cell regeneration. We found that doxycycline (DOX)-induced cell death was sufficient to cause polydipsia, translating even subtle difference in drinking habit into large variations in actual DOX intake among individuals within the same group. Accumulating evidence shows that transient expression of VEGFA enhances cell functional recovery after injury. Therefore, we utilized the chemically modified mRNA (modRNA) technology to enable transient yet efficient VEGFA expression in the pancreas after DOX-induced cell death. Surprisingly, under optimized DOX dose permissive of cell regeneration, VEGFA modRNA only demonstrated marginal benefits on cell functional recovery with large individual variations. We also revealed that the therapeutic efficacy of VEGFA modRNA on cell regeneration was dependent on the degree of cell loss induced by the accumulated DOX intake. Therefore, our results highlight a significant contribution of individual variation in the DTA model and call for attention in evaluating potential efficacy of therapeutic agents in cell regeneration studies. Pancreatic isle Continue reading >>

A Preliminary Report On Oral Glucose Tolerance And Antinociceptive Activity Tests Conducted With Methanol Extract Of Xanthosoma Violaceum Aerial Parts

A Preliminary Report On Oral Glucose Tolerance And Antinociceptive Activity Tests Conducted With Methanol Extract Of Xanthosoma Violaceum Aerial Parts

BMC Complementary and Alternative Medicine Faisal et al.; licensee BioMed Central Ltd.2014 Xanthosoma violaceum is commonly observed in fallow areas of Bangladesh but almost no scientific studies exist on this plant. Rural people consume the plant on a frequent basis. The objective of this study was to scientifically analyze the antinociceptive property of methanol extract of aerial parts of the plant along with antihyperglycemic activity. Antihyperglycemic activity was measured by oral glucose tolerance test (OGTT). Antinociceptive activity was determined by observed decreases in abdominal constrictions in intraperitoneally administered acetic acid-induced pain model in mice. Administration of methanol extract of aerial parts led to dose-dependent and significant reductions in blood glucose levels in glucose-loaded mice. At doses of 50, 100, 200 and 400mg per kg body weight, the extract reduced blood sugar levels by 19.3, 23.2, 31.8, and 47.1%, respectively compared to control animals. By comparison, a standard antihyperglycemic drug, glibenclamide, when administered at a dose of 10mg per kg body weight, reduced blood glucose level by 48.9%. In antinociceptive activity tests, the extract at the above four doses reduced the number of abdominal constrictions by 41.4, 44.8, 48.3, and 55.2%, respectively. A standard pain relieving (antinociceptive) drug, aspirin, reduced the number of writhings by 31.0 and 51.7%, respectively, when administered at doses of 200 and 400mg per kg body weight. To our knowledge, this is the first report on oral glucose tolerance and antinociceptive activity evaluation of aerial parts of the plant. Since the plant is widely available in Bangladesh, the aerial parts can be a readily available source for particularly the rural population for lowe Continue reading >>

Methods And Models For Metabolic Assessment In Mice

Methods And Models For Metabolic Assessment In Mice

Journal of Diabetes Research Volume 2013 (2013), Article ID 986906, 8 pages 1Metabolic Unit, ISIB CNR, 35127 Padova, Italy 2Department of Medicine, Lund University, 221 84 Lund, Sweden Academic Editor: Daisuke Koya Copyright © 2013 G. Pacini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The development of new therapies for the treatment of type 2 diabetes requires robust, reproducible and well validated in vivo experimental systems. Mice provide the most ideal animal model for studies of potential therapies. Unlike larger animals, mice have a short gestational period, are genetically similar, often give birth to many offspring at once and can be housed as multiple groups in a single cage. The mouse model has been extensively metabolically characterized using different tests. This report summarizes how these tests can be executed and how arising data are analyzed to confidently determine changes in insulin resistance and insulin secretion with high reproducibility. The main tests for metabolic assessment in the mouse reviewed here are the glucose clamp, the intravenous and the oral glucose tolerance tests. For all these experiments, including some commonly adopted variants, we describe: (i) their performance; (ii) their advantages and limitations; (iii) the empirical formulas and mathematical models implemented for the analysis of the data arising from the experimental procedures to obtain reliable measurements of peripheral insulin sensitivity and beta cell function. Finally, a list of previous applications of these methods and analytical techniques is provided to better comprehend their use a Continue reading >>

Glucose Dysregulation And Response To Common Anti-diabetic Agents In The Fatzo/pco Mouse

Glucose Dysregulation And Response To Common Anti-diabetic Agents In The Fatzo/pco Mouse

Abstract The FATZO/Pco mouse is the result of a cross of the C57BL/6J and AKR/J strains. The crossing of these two strains and the selective inbreeding for obesity, insulin resistance and hyperglycemia has resulted in an inbred strain exhibiting obesity in the presumed presence of an intact leptin pathway. Routinely used rodent models for obesity and diabetes research have a monogenic defect in leptin signaling that initiates obesity. Given that obesity and its sequelae in humans are polygenic in nature and not associated with leptin signaling defects, the FATZO mouse may represent a more translatable rodent model for study of obesity and its associated metabolic disturbances. The FATZO mouse develops obesity spontaneously when fed a normal chow diet. Glucose intolerance with increased insulin levels are apparent in FATZO mice as young as 6 weeks of age. These progress to hyperglycemia/pre-diabetes and frank diabetes with decreasing insulin levels as they age. The disease in these mice is multi-faceted, similar to the metabolic syndrome apparent in obese individuals, and thus provides a long pre-diabetic state for determining the preventive value of new interventions. We have assessed the utility of this new model for the pre-clinical screening of agents to stop or slow progression of the metabolic syndrome to severe diabetes. Our assessment included: 1) characterization of the spontaneous development of disease, 2) comparison of metabolic disturbances of FATZO mice to control mice and 3) validation of the model with regard to the effectiveness of current and emerging anti-diabetic agents; rosiglitazone, metformin and semaglutide. Conclusion: Male FATZO mice spontaneously develop significant metabolic disease when compared to normal controls while maintaining hyperglyce Continue reading >>

Deletion Variant Of Nicotinamide Nucleotide Transhydrogenase (nnt) Does Not Affect Insulin Secretion Or Glucose Tolerance | Endocrinology | Oxford Academic

Deletion Variant Of Nicotinamide Nucleotide Transhydrogenase (nnt) Does Not Affect Insulin Secretion Or Glucose Tolerance | Endocrinology | Oxford Academic

The C57BL/6J (B6J) strain is the most widely used mouse strain in metabolic research. B6J mice produce a truncated form of nicotinamide nucleotide transhydrogenase (NNT), an enzyme that pumps protons across the inner mitochondrial membrane. It has been proposed that this results in B6J mice having reduced insulin secretion and glucose intolerance compared with other strains of mice (e.g. C3H/HeH and DBA/2) that have a full-length NNT. The aim of this study was to determine whether truncated NNT was associated with reduced insulin secretion and glucose intolerance, comparing B6 substrains that differ in having a truncated NNT. C57BL/6N (B6N) mice have wild-type Nnt. We compared Nnt expression and activity levels as well as in vivo insulin secretion and glucose tolerance between these mice and B6J. Body weights and specific fat-pad depot masses were alike and Nnt expression and activity levels were similar between B6N and B6J mice. Glucose-mediated insulin secretion and insulin sensitivity were comparable between the two groups of mice, as were plasma glucose and insulin levels during the oral glucose tolerance test. The presence of a truncated Nnt did not affect insulin secretion or glucose tolerance on the C57BL/6 background. We suggest that low or normal levels of NNT (regardless of truncation) have little effect on insulin secretion. Rather, it is the increase in expression of Nnt that regulates and enhances insulin secretion. Our data confirm that B6J is a reasonable control strain for diabetes research; this is especially important considering that it is the strain commonly used to generate genetically modified animals. The use of genetically modified mouse models to study mechanisms of complex diseases such as diabetes and obesity has increased substantially in re Continue reading >>

Glucose Tolerance Test In Mice

Glucose Tolerance Test In Mice

Glucose tolerance test is a standard procedure that addresses how quickly exogenous glucose can be cleared from blood. Specifically, uptake of glucose from the blood by cells is regulated by insulin. Impairment of glucose tolerance (i.e, longer time to clear given amount of glucose) indicates problems with maintenance of glucose homeostasis (insulin resistance, carbohydrate metabolism, diabetes, etc). According to the WHO, in a standard oral glucose tolerance test (OGTT), glucose level should be below 7.8 mmol/L (140 mg/dl) at 2 h. Levels between this and 11.1 mmol/L (200 mg/dl) indicate “impaired glucose tolerance”, and any level above 11.1 mmol/L (200 mg/dl) confirms a diagnosis of diabetes. Materials and reagents Mice (~20 C57BL/6J (B6) males of 2-3 months old) 70% ethanol Beta-D(+)-glucose (Sigma-Aldrich, catalog number: G8270 ) NaCl KCl Sodium phosphate Phosphate buffered saline (PBS) (see Recipes) Equipment ACCU-CHEK comfort curve glucometer (Roche Diagnostics, catalog number: 03537536001 ) (this product has been discontinued. Any new product of ACCU-CHEK should work fine as well) Such device quantifies glucose amperometrically by measuring the current produced upon oxidation of glucose to gluconic acid by glucose oxidase, or to gluconolactone by dehydrogenase. 27 gauge needle (Single-Use Needles, supplied by VWR, BD Medical, catalog number: BD305109 ) Microvette CB300 Z serum separator (SARSTEDT, catalog number: 16.440.100 ) Acrodisc 25 mm syringe filters w/ 0.2 μM HT Tuffryn membrane (Pall Corporation, catalog number: 4192 ) Procedure Note: All the following experimental procedures that involve animals (rodents) should receive approval from IACUC or equivalent committee. Humane treatment of animals should be practiced all the time. In the Cavener lab, we us Continue reading >>

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