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How To Induce Type 2 Diabetes In Mice

Development Of A Nongenetic Mouse Model Of Type 2 Diabetes

Development Of A Nongenetic Mouse Model Of Type 2 Diabetes

Development of a Nongenetic Mouse Model of Type 2 Diabetes Department of Human Nutrition, Foods and Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA Received 1 August 2011; Accepted 30 August 2011 Copyright 2011 Elizabeth R. Gilbert 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. Insulin resistance and loss of -cell mass cause Type 2 diabetes (T2D). The objective of this study was to generate a nongenetic mouse model of T2D. Ninety-six 6-month-old C57BL/6N males were assigned to 1 of 12 groups including (1) low-fat diet (LFD; low-fat control; LFC), (2) LFD with 1 i.p. 40 mg/kg BW streptozotocin (STZ) injection, (3), (4), (5), (6) LFD with 2, 3, 4, or 5 STZ injections on consecutive days, respectively, (7) high-fat diet (HFD), (8) HFD with 1 STZ injection, (9), (10), (11), (12) HFD with 2, 3, 4, or 5 STZ injections on consecutive days, respectively. After 4 weeks, serum insulin levels were reduced in HFD mice administered at least 2 STZ injections as compared with HFC. Glucose tolerance was impaired in mice that consumed HFD and received 2, 3, or 4 injections of STZ. Insulin sensitivity in HFD mice was lower than that of LFD mice, regardless of STZ treatment. Islet mass was not affected by diet but was reduced by 50% in mice that received 3 STZ injections. The combination of HFD and three 40 mg/kg STZ injections induced a model with metabolic characteristics of T2D, including peripheral insulin resistance and reduced -cell mass. It is estimated that 23.6 million or 8% of the American population suffers from diabetes [ 1 ]. Almost the same numbers have pre Continue reading >>

Springerprotocols: Abstract: Experimentally Induced Rodent Models Of Type 2 Diabetes

Springerprotocols: Abstract: Experimentally Induced Rodent Models Of Type 2 Diabetes

World Health Organization (2010) Facts and figures about diabetes. Accessed 5 Dec 2011 Pinhas-Hamiel O, Zeitler O (2005) The global spread of type 2 diabetes mellitus in children and adolescents. J Pediatr 146:693700 Moore KR et al (2003) Three-year prevalence and incidence of diabetes among American Indian youth in Montana and Wyoming 1999 to 2001. J Pediatr 143:368371 Krosnick A (2000) The diabetes and obesity epidemic among the Pima Indians. N J Med 97:3137 Srinivasan K et al (2005) Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res 52:313320 Wall RJ, Shani M (2008) Are animal models as good as we think? Theriogenology 69:29 Islam MS, Loots DT (2009) Experimental rodent models of type 2 diabetes: a review. Methods Find Exp Clin Pharmacol 31:249261 Goldner MG, Gomori G (1943) Alloxan diabetes in the dog. Endocrinology 33:297308 Rerup CC (1970) Drugs producing diabetes through damage of the insulin secreting cells. Pharmacol Rev 22:485518 Rees DA, Alcolado JC (2005) Animal models of diabetes mellitus. Diabet Med 22:359370 Bolzan AD, Bianchi MS (2002) Genotoxicity of streptozotocin. Mutat Res 512:121134 Portha B et al (1974) Diabetogenic effect of streptozotocin in the rat during the perinatal period. Diabetes 23:889895 Portha B, Picon L, Rosselin G (1979) Chemical diabetes in the adult rat as the spontaneous evolution of neonatal diabetes. Diabetologia 17:371377 Iwase M et al (1986) A new model of type 2 (non-insulin-dependent) diabetes mellitus in spontaneously hypertensive rats: diabetes induced by neonatal streptozotocin injection. Diabetologia 29:808811 Giddings SJ et al (1985) Impaired insulin biosynthetic capacity in a rat model for non-insulin-dependent diabetes. Stu Continue reading >>

Histone Deacetylase Inhibition Of Cardiac Autophagy In Rats On A Highfat Diet With Lowdose Streptozotocin-induced Type 2 Diabetes Mellitus

Histone Deacetylase Inhibition Of Cardiac Autophagy In Rats On A Highfat Diet With Lowdose Streptozotocin-induced Type 2 Diabetes Mellitus

Histone deacetylase inhibition of cardiac autophagy in rats on a highfat diet with lowdose streptozotocin-induced type 2 diabetes mellitus Affiliations: Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C., School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C., Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan, R.O.C., Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei 11696, Taiwan, R.O.C., Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C., Division of Cardiology, TzuChi General Hospital, Institute of Medical Sciences, TzuChi University, Hualien 97004, Taiwan, R.O.C., Division of Endocrinology and Metabolism, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei City 22174, Taiwan, R.O.C. Published online on: October 26, 2017 Metrics: HTML 0 views | PDF 0 views Cited By (CrossRef): 0 citations Autophagy serves a role in preserving cellular homeostasis. Diabetes mellitus (DM) impairs cardiac autophagy and is associated with an accumulation of cytotoxic proteins that may provoke apoptosis and damage cardiomyocytes. Histone deacetylase (HDAC) inhibitors attenuate cardiac fibrosis and inflammation, and improve cardiomyopathy resulting from DM. However, the effect of HDAC inhibition on autophagy in DM cardiomyopathy has not been investigated. The purpose of the present study was to evaluate whether HDAC inhibition modulates cardiac autophagy and to investigate the potential mechanisms in type 2 DM (T2DM) hearts. Electrocardiography was used to evaluate cardiac functi Continue reading >>

A New Method For Targeted And Sustained Induction Of Type 2 Diabetes In Rodents

A New Method For Targeted And Sustained Induction Of Type 2 Diabetes In Rodents

A New Method for Targeted and Sustained Induction of Type 2 Diabetes in Rodents Scientific Reportsvolume7, Articlenumber:14158 (2017) Type 2 diabetes is a chronic metabolic disorder that is becoming a leading cause of morbidity and mortality. The prolonged time-course of human type 2 diabetes makes modelling of the disease difficult and additional animal models and methodologies are needed. The goal of this study was to develop and characterise a new method that allows controlled, targeted and sustained induction of discrete stages of type 2 diabetes in rodents. Using adult, male rats, we employed a three-week high fat-diet regimen and confirmed development of obesity-associated glucose intolerance, a key feature of human type 2 diabetes. Next, we utilised osmotic mini-pumps to infuse streptozotocin (STZ; doses ranging 80200 mg/kg) over the course of 14-days to decrease insulin-producing capacity thus promoting hyperglycemia. Using this new approach, we demonstrate a dose-dependent effect of STZ on circulating glucose and insulin levels as well as glucose tolerance, while retaining a state of obesity. Importantly, we found that insulin secretion in response to a glucose load was present, but reduced in a dose-dependent manner by increasing STZ. In conclusion, we demonstrate a novel method that enables induction of discrete stages of type 2 diabetes in rodents that closely mirrors the different stages of type 2 diabetes in humans. Among the different forms of diabetes, type 2 diabetes accounts for approximately 90% of cases and current estimates indicate that by 2040, approximately 642 million world-wide people will be living with type 2 diabetes 1 , 2 . This is likely to be a conservative estimate given that for every case of diagnosed type 2 diabetes, we know there is Continue reading >>

Extract Of Ginkgo Biloba Ameliorates Streptozotocin-induced Type 1 Diabetes Mellitus And High-fat Diet-induced Type 2 Diabetes Mellitus In Mice

Extract Of Ginkgo Biloba Ameliorates Streptozotocin-induced Type 1 Diabetes Mellitus And High-fat Diet-induced Type 2 Diabetes Mellitus In Mice

Int J Med Sci 2015; 12(12):987-994. doi:10.7150/ijms.13339 Extract of Ginkgo Biloba Ameliorates Streptozotocin-Induced Type 1 Diabetes Mellitus and High-Fat Diet-Induced Type 2 Diabetes Mellitus in Mice Ki-Jong Rhee1, Chang Gun Lee1, Sung Woo Kim2, Dong-Hyeon Gim3, Hyun-Cheol Kim3, Bae Dong Jung2,3, 1. Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University at Wonju 2. Department of Animal Science, North Carolina State University 3. College of Veterinary Medicine & Institute of Veterinary Science, Kangwon National University This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License . See for full terms and conditions. Rhee KJ, Lee CG, Kim SW, Gim DH, Kim HC, Jung BD. Extract of Ginkgo Biloba Ameliorates Streptozotocin-Induced Type 1 Diabetes Mellitus and High-Fat Diet-Induced Type 2 Diabetes Mellitus in Mice. Int J Med Sci 2015; 12(12):987-994. doi:10.7150/ijms.13339. Available from Diabetes mellitus (DM) is caused by either destruction of pancreatic -cells (type 1 DM) or unresponsiveness to insulin (type 2 DM). Conventional therapies for diabetes mellitus have been developed but still needs improvement. Many diabetic patients have complemented conventional therapy with alternative methods including oral supplementation of natural products. In this study, we assessed whether Ginkgo biloba extract (EGb) 761 could provide beneficial effects in the streptozotocin-induced type 1 DM and high-fat diet-induced type 2 DM murine model system. For the type 1 DM model, streptozotocin-induced mice were orally administered EGb 761 for 10 days prior to streptozotocin injection and then again administered EGb 761 for an additional 10 days. Streptozotocin-treated mice administered EGb 761 exhibi Continue reading >>

[full Text] Streptozotocin-induced Type 1 Diabetes In Rodents As A Model For Study | Dmso

[full Text] Streptozotocin-induced Type 1 Diabetes In Rodents As A Model For Study | Dmso

Editor who approved publication: Professor Ming-Hui Zou Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, USA Abstract: Chronic hyperglycemia and the corresponding glucotoxicity are the main pathogenic mechanisms of diabetes and its complications. Streptozotocin (STZ)-induced diabetic animal models are useful platforms for the understanding of cell glucotoxicity in diabetes. As diabetes induced by a single STZ injection is often referred to as type 1 diabetes that is caused by STZs partial destruction of pancreas, one question often being asked is whether the STZ type 1 diabetes animal model is a good model for studying the mitochondrial mechanisms of cell glucotoxicity. In this mini review, we provide evidence garnered from the literature that the STZ type 1 diabetes is indeed a suitable model for studying mitochondrial mechanisms of diabetic cell glucotoxicity. Evidence presented includes: 1) continued cell derangement is due to chronic hyperglycemia after STZ is completely eliminated out of the body; 2) STZ diabetes can be reversed by insulin treatment, which indicates that cell responds to treatment and shows ability to regenerate; and 3) STZ diabetes can be ameliorated or alleviated by administration of phytochemicals. In addition, mechanisms of STZ action and fundamental gaps in understanding mitochondrial mechanisms of cell dysfunction are also discussed. Keywords: diabetes, cell, glucotoxicity, mitochondria, redox imbalance, streptozotocin Diabetes mellitus and its complications are chronic glucotoxicity diseases. The concept of cell glucotoxicity (and other cells as well) implicates that persistent excessive glucose can exert adverse or toxic effect on cell function after the Continue reading >>

The Use Of Animal Models In The Study Of Diabetes Mellitus

The Use Of Animal Models In The Study Of Diabetes Mellitus

Abstract Animal models have enormously contributed to the study of diabetes mellitus, a metabolic disease with abnormal glucose homeostasis, due to some defect in the secretion or the action of insulin. They give researchers the opportunity to control in vivo the genetic and environmental factors that may influence the development of the disease and establishment of its complications, and thus gain new information about its handling and treatment in humans. Most experiments are carried out on rodents, even though other species with human-like biological characteristics are also used. Animal models develop diabetes either spontaneously or by using chemical, surgical, genetic or other techniques, and depict many clinical features or related phenotypes of the disease. In this review, an overview of the most commonly used animal models of diabetes are provided, highlighting the advantages and limitations of each model, and discussing their usefulness and contribution in the field of diabetes research. Type I Diabetes (T1DM) Models T1DM, a multifactorial autoimmune disease involving genetic and environmental factors, is hallmarked by T-cell and macrophages-mediated destruction of pancreatic β-cells, resulting in irreversible insulin deficiency. Diabetic ketoacidosis, a T1DM immediate consequence, can be fatal without treatment, while the long-term vascular T1DM complications affecting several organs and tissues can significantly affect life expectancy. There is no doubt that T1DM susceptibility is MHC-dependent and MHC genes account for approximately 50% of the total contribution to the disease. However, although to date studies corroborate that both HLA-DR and HLA-DQ genes are important in determining disease risk, the effects of individual alleles may be modified by the h Continue reading >>

Streptozotocin/high Fat Diet-induced Type 2 Diabetes

Streptozotocin/high Fat Diet-induced Type 2 Diabetes

Home Streptozotocin/High Fat Diet-induced Type 2 Diabetes | Bienta Streptozotocin/High Fat Diet-induced Type 2 Diabetes Background: Unlike type 1 diabetes, type 2 diabetes (T2D) is associated with resistance to insulin action. To develop the corresponding animal pathology model, High Fat Diet (HFD) is often used. HFD leads to the development of obesity, metabolic syndrome and decrease in insulin sensitivity in mice, in contrast to low fat diet (LFD). Combination of HFD and single streptozotocin (STZ) injection leads to metabolic changes that are characteristic of Type 2 Diabetes, including peripheral insulin resistance and pancreas -cell impairment. HFD/STZ-induced model of experimental T2D can be used for efficacy testing of anti-diabetic and anti-obesity drugs. The induction of disease can be carried out in rats or mice. This model is suitable not only for the study of the effectiveness of the drugs stimulating the production/release of insulin from beta cells, but also drugs that reduce the production of glucose in the liver, improve the sensitivity of tissues to insulin, regulate the production of incretins, etc. Service details: To induce T2D in C57BL/6 mice, the standard HFD (Research Diets, Inc.) in combination with a single high dose (95 mg/kg) of STZ is used. Development of the diabetic state is monitored by routine tests food and water intake, body weight gain, glucose levels, glycosylated hemoglobin in the blood, GTT and ITT. Various markers of diabetes side effects can be monitored upon request. To develop the HFD/STZ model of Type 2 diabetes for testing a drug candidate, we suggest using 8-10 animals per each planned experimental group, 12 weeks of high fat diet for obesity induction and post-HFD/STZ treatment monitoring to confirm that the mice are diabet Continue reading >>

High Fat Diet/stz Induced Diabetic Model

High Fat Diet/stz Induced Diabetic Model

Home / Lead Optimization / Pharmacology and Pharmacodynamics Studies / Rodent Models / Non-Genetically Engineering Models (NON-GEMs) / Rodent Metabolic Disease Models / High Fat Diet/STZ Induced Diabetic Model Creative Biolabs has extensive experience in establishing chemically induced diabetic mice/rats models for our global customers, especially for the high fat diet/STZ induced diabetic model. Type 2 diabetes is a long-term metabolic disorder characterized by high blood sugar, insulin resistance and relative lack of insulin. Now there has been a tragic increase in diabetes worldwide, paralleling the overweight and obesity epidemic. In order to further elucidate the pathobiology and to find better treatments and novel prevention strategies for this complex disease, appropriate experimental animal models are of great value. One example of type 2 diabetes animal models is the high fat diet-fed, streptozotocin (HFD/STZ)-treated rat model. Rats fed with high-fat diet are useful models to mimic insulin resistance, which is one of the important features of type 2 diabetes. At the same time, high-dose streptozotocin (STZ) is widely used to induce type 1 diabetes in adult mice, resulting from the cell death through alkylation of DNA. However, low-dose STZ has been shown to induce a mild impairment of insulin secretion, which is similar to the feature of the later stage of type 2 diabetes. Based on the above two points, investigators have started to develop a new diabetic model by the combination of diet (high fat or high fructose diet) plus the treatment of STZ. In the first place, rats are fed with above special diets, which initially produces hyperinsulinemia and insulin resistance. Subsequently, these sensitive subjects are treated with low-dose STZ that causes the cell d Continue reading >>

Choosing Among Type Ii Diabetes Mouse Models

Choosing Among Type Ii Diabetes Mouse Models

JAX has been distributing mouse models for type II diabetes (Non-insulin Dependent Diabetes; NIDD; T2D) since the 1960s, and today there are several models to choose from. Unfortunately, no single diabetic mouse model recapitulates all of the features or complications of human diabetes. How, then, do you choose which model (or models) to use in your research? Indeed, one of the most common diabetes-related questions we receive in Technical Information is “Which diabetes model is ‘The Best’?” Below is a broad overview of diabetes models that are available from JAX and some considerations to help you to make your decision. Diabetes Phase I, II or III? First some orientation: Diabetes in humans typically develops through a progressive series of increasingly severe stages (or phases): • Pre-diabetes: Characterized by impaired glucose tolerance – difficulty clearing glucose following a meal – postprandial hyperglycemia, and (or) decreased sensitivity to insulin. • Phase I: Postprandial as well as basal hyperglycemia; insulin-producing beta cells in the pancreas are increasingly dysfunctional. • Phase II: Fasting hyperglycemia and significant beta cell atrophy. • Phase III (end stage): Beta cells can no longer release insulin; insulin replacement therapy is required. Choosing an appropriate diabetes model depends on the severity of diabetes you wish to study. As in humans, mouse models of T2D are obese, but vary in severity – some models are morbidly obese, whereas others manifest more moderate obesity. Diet-induced Obesity (DIO) Mice: Modeling Pre-Diabetes Obesity is one of the greatest risk factors linked to diabetes in humans, and similar to humans, some mouse strains become obese when fed high-fat or so-called “Western” diets. Among mouse strains Continue reading >>

Streptozotocin/high Fat Diet Model Of Type 2 Diabetes

Streptozotocin/high Fat Diet Model Of Type 2 Diabetes

Streptozotocin/High Fat Diet Model of Type 2 Diabetes Recently, non-genetic rodent models have been developed which combine exposure to a high-fat diet with low doses of streptozotocin (STZ), a toxin that specifically targets the insulinproducing -cells of the pancreas and destroys them through alkylation of DNA. These models are popular because they more closely mirror the metabolic disturbances observed in type 2 diabetic patients when compared to monogenetic rodent models of diabetes/obesity or dietary-induced obese rats and mice alone (which model insulin resistance but are not overtly diabetic). We have validated STZ/high fat diet models of type 2 diabetes in both mice and rats. High fat fed animals treated with STZ display impaired glucose tolerance following a glucose challenge.Plasma insulin levels are markedly reduced in the animals given STZ compared to the vehicle-treated control group on the high fat diet. STZ-treated mice on high fat diet exhibit significantly increased urinary glucose excretion and HbA1c compared to control animals. Our STZ/ high fat diet models of type 2 diabetes have been validated by showing that STZ treatment markedly reduces pancreatic insulin and insulin-secreting -cells. The STZ/high fat model can therefore be used to screen for the beneficial effects of novel antidiabetic compounds on glycaemic control and to assess the ability of novel antidiabetic drugs to preserve -cell function. It can also be used to examine the effects of drugs on diabetic complications. Please contact us for further information about our streptozotocin/high fat diet models of type 2 diabetes. Poucher et al. 2010. Preservation of pancreatic beta cell-mass in high fat-fed STZ treated mice by the dipeptidyl peptidase-4 inhibitors saxagliptin and sitagliptin. P Continue reading >>

Melior Discovery: Db/db Mouse Model Of Type Ii Diabetes

Melior Discovery: Db/db Mouse Model Of Type Ii Diabetes

Type II diabetes is characterized by high blood glucose levels in the presence of normal or elevated serum insulin levels. There are many animal models of type II diabetes that involve administering high levels of glucose to otherwise normoglycemic mice (see OGTT mouse model ). db/db mice express mutations in leptin receptor that lead to decreased insulin receptor sensitivity and subsequent increased levels of blood glucose, decreased -cell function, increased obesity and elevated HBA1c levels. Compounds from several structural classes can effectively regulate this hyperglycemic response including sulfonylureas, thiazoladinediones (PPAR agonists; glitazones) and metformin (glucophage). These drug classes are also clinically approved for use in humans. The above data illustrate the effects of rosiglitazone, an antidiabetic drug in the thiazolidinedione class, across time in db/db mice. Initially both vehicle and rosiglitazone treated mice exhibit similar blood glucose levels (days 0 & 5). However, by day 10 mice treated with rosiglitazone have significantly decreased blood glucose levels relative to vehicle treated mice. This effect is maintained throughout the study, illustrating the ability of antidiabetic drugs to decrease blood glucose in mice with diabetic like physiology. Data are mean SEM; ***p<0.001 compared to baseline, +++p<0.001 compared to vehicle. If you are interested in learning moreabout the db/db Mouse Model, please contact [email protected] to start the conversation today. Continue reading >>

The Use Of Animal Models In Diabetes Research

The Use Of Animal Models In Diabetes Research

The use of animal models in diabetes research Diabetes Research Group, King's College London, London, UK Aileen King, Diabetes Research Group, Guy's Campus, King's College London, London SE1 1UL, UK. E-mail: [email protected] Received 2011 Aug 19; Revised 2012 Feb 10; Accepted 2012 Feb 13. Copyright 2012 The Author. British Journal of Pharmacology 2012 The British Pharmacological Society This article has been cited by other articles in PMC. Diabetes is a disease characterized by a relative or absolute lack of insulin, leading to hyperglycaemia. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is due to an autoimmune destruction of the insulin-producing pancreatic beta cells, and type 2 diabetes is caused by insulin resistance coupled by a failure of the beta cell to compensate. Animal models for type 1 diabetes range from animals with spontaneously developing autoimmune diabetes to chemical ablation of the pancreatic beta cells. Type 2 diabetes is modelled in both obese and non-obese animal models with varying degrees of insulin resistance and beta cell failure. This review outlines some of the models currently used in diabetes research. In addition, the use of transgenic and knock-out mouse models is discussed. Ideally, more than one animal model should be used to represent the diversity seen in human diabetic patients. This paper is the latest in a series of publications on the use of animal models in pharmacology research. Readers might be interested in the previous papers. Robinson V (2009). Less is more: reducing the reliance on animal models for nausea and vomiting research. Holmes AM, Rudd JA, Tattersall FD, Aziz Q, Andrews PLR (2009). Opportunities for the replacement of animals in the study of nausea and vomiting. Continue reading >>

Streptozotocin-induced Diabetes In Human Apolipoprotein B Transgenic Mice: Effects On Lipoproteins And Atherosclerosis

Streptozotocin-induced Diabetes In Human Apolipoprotein B Transgenic Mice: Effects On Lipoproteins And Atherosclerosis

Streptozotocin-induced diabetes in human apolipoprotein B transgenic mice: effects on lipoproteins and atherosclerosis Department of Medicine, Division of Nutrition and Preventive Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032 1 To whom correspondence should be addressed. The effects of diabetes and lipoprotein lipase (LpL) on plasma lipids were studied in mice expressing human apolipoprotein B (HuBTg). Our overall objective was to produce a diabetic mouse model in which the sole effects of blood glucose elevation on atherosclerosis could be assessed. Mice were made diabetic by intraperitoneal injection of streptozotocin, which led to a 2- to 2.5-fold increase in plasma glucose. Lipids were assessed in mice on chow and on an atherogenic Western type diet (WTD), consisting of 21% (wt/wt) fat and 0.15% (wt/wt) cholesterol. Plasma triglyceride and cholesterol were the same in diabetic and non-diabetic mice on the chow diet. On the WTD, male diabetic HuBTg mice had a >50% increase in plasma cholesterol and more very low density lipoprotein (VLDL) cholesterol and triglyceride as assessed by FPLC analysis. A Triton study showed no increase in triglyceride or apolipoprotein B production, suggesting that the accumulation of VLDL was due to a decrease in lipoprotein clearance. Surprisingly, the VLDL increase in these mice was not due to a decrease in LpL activity in postheparin plasma. To test whether LpL overexpression would alter these diabetes-induced lipoprotein changes, HuBTg mice were crossed with mice expressing human LpL in muscle. LpL overexpression reduced plasma triglyceride, but not cholesterol, in male mice on WTD. Aortic root atherosclerosis assessed in 32-week-old mice on the WTD was not greater in diab Continue reading >>

Modified Dio Protocols Improve Type 2 Diabetes Models

Modified Dio Protocols Improve Type 2 Diabetes Models

Modified DIO Protocols Improve Type 2 Diabete... Modified DIO Protocols Improve Type 2 Diabetes Models Animal models of diet-induced obesity (DIO) are commonly used to model metabolic syndrome, but have some limitations. Can a modified DIO protocol produce better type 2 diabetes models? DIO C57BL/6 mice are obese, glucose intolerant, insulin resistant, and display mild hyperglycemia. To better model Type 2 diabetes, researchers at the University of Colorado and NYU Langone Medical Center recently developed a modified protocol which combines diet induction and streptozotocin treatment in C57BL/6NTac mice . Yu and colleagues obtained DIO B6 mice from Taconic Biosciences and continued feeding the high fat diet D12492 for an additional five weeks. Some mice were then administered low doses of streptozotocin (STZ), a drug which is commonly used to induce Type 1 diabetes by destroying pancreatic beta cells. In this case, the lower STZ dose produced less severe insulin deficiency. The modified protocol of high fat diet + low dose STZ produced mice with higher blood glucose levels and plasma triglycerides compared to Black 6 mice on high fat diet alone. The high fat diet + STZ mice also demonstrated mild body weight loss (~10%). Researchers evaluated the new model by studying its response to canaglifozin, a diabetes treatment which works by inhibiting sodium-glucose transporter 2 ( SGLT2 ). In the clinic, canaglifozin controls hyperglycemia, with some improvement also in lipid profiles. As in humans, treatment of the high fat diet + STZ mice with canaglifozin resulted in lower blood glucose. They also showed lower total plasma cholesterol compared to mice treated with either insulin or a placebo. Although canaglifozin treatment decreased plasma triglycerides in some clinical s Continue reading >>

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