C57BL/6 mice fed high fat diets as models for diabetes-accelerated atherosclerosis

Schreyer, Sandra A.; Wilson, Deborah; LeBoeuf, Renée C.

doi:10.1016/s0021-9150(97)00165-2

Cited by 163 publications

(144 citation statements)

References 22 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…Generally, it is a high cholesterol diet, not a diabetogenic diet, that induces atherosclerosis in the C57BL/6 mouse model (19). It is apparent from our histological data that L-PGDS KO mice had increased fat deposition as well as a thickening of the aortic media, which was not evident in C57BL/6 mice after 20 weeks on the diabetogenic diet (Figs.…”

Section: Discussionmentioning

confidence: 67%

See 1 more Smart Citation

Accelerated Glucose Intolerance, Nephropathy, and Atherosclerosis in Prostaglandin D2 Synthase Knock-out Mice

Ragolia

Palaia

Hall

et al. 2005

Journal of Biological Chemistry

109

View full text Add to dashboard Cite

Type 2 diabetics have an increased risk of developing atherosclerosis, suggesting the mechanisms that cause this disease are enhanced by insulin resistance. In this study we examined the effects of gene knock-out (KO) of lipocalin-type prostaglandin D 2 synthase (L-PGDS), a protein found at elevated levels in type 2 diabetics, on diet-induced glucose tolerance and atherosclerosis. Our results show that L-PGDS KO mice become glucose-intolerant and insulin-resistant at an accelerated rate when compared with the C57BL/6 control strain. Adipocytes were significantly larger in the L-PGDS KO mice compared with controls on the same diets. Cell culture data revealed significant differences between insulinstimulated mitogen-activated protein kinase phosphatase-2, protein-tyrosine phosphatase-1D, and phosphorylated focal adhesion kinase expression levels in L-PGDS KO vascular smooth muscle cells and controls. In addition, only the L-PGDS KO mice developed nephropathy and an aortic thickening reminiscent to the early stages of atherosclerosis when fed a "diabetogenic" high fat diet. We conclude that L-PGDS plays an important role regulating insulin sensitivity and atherosclerosis in type 2 diabetes and may represent a novel model of insulin resistance, atherosclerosis, and diabetic nephropathy.Cardiovascular disease is the primary cause of morbidity and mortality in people with non-insulin-dependent diabetes mellitus (1). Type 2 diabetics have a significantly increased risk of developing hypertension, atherosclerosis, and restenosis after angioplasty or stent implantation (2, 3). These phenomena are partially attributable to the abnormal accumulation of vascular smooth muscle cells (VSMCs) 1 within the intima of blood vessels resulting from alterations in migration, proliferation, and apoptosis (4, 5).Previously, we have demonstrated that lipocalin-type prostaglandin D 2 synthase (L-PGDS) inhibits the exaggerated growth phenotype of VSMCs isolated from hypertensive rats (6). The mechanism appears to involve the inhibition of insulinstimulated protein kinase B (Akt) and glycogen synthase kinase-3␤ phosphorylation (6). We have also shown that VSMC apoptosis and migration are both altered by L-PGDS and that any beneficial effects of L-PGDS are absent in VSMCs isolated from diabetic animals (7). In addition, L-PGDS is ultimately responsible for the synthesis of the naturally occurring peroxisome proliferator activator receptor ␥ ligand, 15-deoxy-⌬ 12,14 prostaglandin J 2 , already known to induce apoptosis (8). Moreover, thiazolidinediones, which are synthetic peroxisome proliferator activator receptor ␥ ligands, have been shown to increase insulin sensitivity and enhance insulin-stimulated glucose transport into muscle (9) and exert other beneficial cardiovascular effects such as blocking VSMC growth and migration to delay the onset of atherosclerosis (10, 11).Several other findings have emerged suggesting that L-PGDS has important vascular functions. Inoue et al. (12) have demonstrated that elevated serum L-PGDS levels co...

show abstract

Section: Discussionmentioning

confidence: 67%

“…The C57BL/6 mouse strain represents one model to study diet-induced atherosclerosis and diabetes (19). After 20 weeks on a high fat (42% kcal) diabetogenic diet the mice become hyperglycemic, insulin-resistant, and obese.…”

mentioning

confidence: 99%

Accelerated Glucose Intolerance, Nephropathy, and Atherosclerosis in Prostaglandin D2 Synthase Knock-out Mice

Ragolia

Palaia

Hall

et al. 2005

Journal of Biological Chemistry

109

View full text Add to dashboard Cite

show abstract

“…High-fat diets produce insulin resistant diabetes in mice with elevated blood sugars between 180 and 300 mg/dL that are in the range seen in human type 2 diabetes. 76 However, the response to this diet is strain-dependent; C57BL6, the strain used for most atherosclerosis and cardiomyopathy studies, is relatively resistant to diet induced hyperglycemia. Moreover, a number of genetic modifications leading to diabetes show diminished or no effect in this strain.…”

Section: Do Mouse Models Reproduce the Relationship Between Diabetes mentioning

confidence: 99%

Diabetic Vascular Disease

Goldberg

Dansky

2006

ATVB

View full text Add to dashboard Cite

Abstract-It is well known that humans with diabetes have more atherosclerosis and its complications. The causes of this relationship are, however, unclear. Although recent data show that improved glycemic control reduces arterial disease in type 1 diabetes, other studies have shown that subjects with "prediabetes" have more cardiovascular disease before the development of hyperglycemia. Thus, either hyperglycemia and/or lack of insulin actions are toxic to arteries, or metabolic derangements exclusive of hyperglycemia are atherogenic. For Ͼ50 years animal models of diabetes and atherosclerosis have been used to uncover potential mechanisms underlying diabetes associated cardiovascular disease. Surprisingly, diabetes alone increases vascular disease in only a few select animal models. Increased atherosclerosis has been found in several animals and lines of genetically modified mice; however, diabetes often also leads to greater hyperlipidemia. This makes it difficult to separate the toxic effects of insulin lack and/or hyperglycemia from those caused by the lipids. These studies are reviewed, as well as more recent investigations using new methods to create diabetic-atherosclerotic models.

show abstract

“…The mechanism by which diabetes accelerates the development of atherosclerosis needs to be further elucidated. Satisfactory animal models for studying the relationship between components of diabetes, such as insulin resistance, dyslipidemia, and the occurrence and progression of atherosclerosis, are currently sparse [4][5][6].The cholesterol-fed rabbit has been a widely used model for experimental atherosclerosis research [7]. This model can be combined with a number of other methods causing endothelial dysfunction, diabetes, artificial hypertension, or infection [7].…”

mentioning

confidence: 99%

mentioning

confidence: 99%

A Diet High in Saturated Fat and Sucrose Alters Glucoregulation and Induces Aortic Fatty Streaks in New Zealand White Rabbits

Yin

Yuan

Wang

et al. 2002

Journal of Diabetes Research

View full text Add to dashboard Cite

A new and convenient animal model for studying peripheral vascular and coronary artery disease in diabetes was established in this study. Male New Zealand White rabbits weighing approximately 2 kg were divided into 2 groups: a normal control group fed standard laboratory chow and a diabetogenic diet-fed group received a high-fat/high-sucrose diet. The high-fat/high-sucrose diet (contained 10% lard and 37% sucrose) feeding was maintained for 6 months. Plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, superoxide dismutase, nitric oxide, nitric oxide synthase, insulin, and glucose were quantitated at monthly or bimonthly intervals. The aortic fatty streak lesions were quantified following lipid staining with Sudan IV. The aortic samples were observed by electron microscopy. High plasma triglyceride and glucose concentrations were induced. At the end of 6 months, the aortic fatty streak lesions were present in the animals' vascular specimens. As far as we know, this is the first report that demonstrates that New Zealand White rabbits can develop obvious aortic fatty streaks by feeding a high-fat/high-sucrose diet. Our results suggest that New Zealand White rabbits fed a high-fat/high-sucrose diet would provide a convenient model for studying peripheral vascular and coronary artery disease in diabetes. Type 2 diabetes (non-insulin-dependent diabetes mellitus, NIDDM) is a major risk factor for atherosclerosis. At equivalent conventional risk levels, there is a 4-to 5-fold increase in the mortality from vascular disease in diabetic patients, for example, coronary heart disease caused by atherosclerosis [1,2]. There is also evidence that elevated triglycerides is an important cardiovascular risk factor, especially in diabetics [3]. The mechanism by which diabetes accelerates the development of atherosclerosis needs to be further elucidated. Satisfactory animal models for studying the relationship between components of diabetes, such as insulin resistance, dyslipidemia, and the occurrence and progression of atherosclerosis, are currently sparse [4][5][6].The cholesterol-fed rabbit has been a widely used model for experimental atherosclerosis research [7]. This model can be combined with a number of other methods causing endothelial dysfunction, diabetes, artificial hypertension, or infection [7]. Nevertheless, to our knowledge, the rabbit has not previously been used to induce hyperglycemia by a diet high in saturated fat and glucose for the study of diabetes associated atherosclerosis.In this study, New Zealand White rabbits were fed a highfat/high-sucrose diet for up to 6 months, and the plasma parameters and the development of aortic fatty streak lesions were investigated. Ultrastructural pathological changes were also studied. We demonstrate that this diet induced an altered plasma lipoprotein profile, hyperglycemia, and obvious aortic fatty streak lesions in the rabbits. 179

show abstract

C57BL/6 mice fed high fat diets as models for diabetes-accelerated atherosclerosis

Cited by 163 publications

References 22 publications

Accelerated Glucose Intolerance, Nephropathy, and Atherosclerosis in Prostaglandin D2 Synthase Knock-out Mice

Accelerated Glucose Intolerance, Nephropathy, and Atherosclerosis in Prostaglandin D2 Synthase Knock-out Mice

Diabetic Vascular Disease

A Diet High in Saturated Fat and Sucrose Alters Glucoregulation and Induces Aortic Fatty Streaks in New Zealand White Rabbits

Contact Info

Product

Resources

About