The db/db mouse, a model for diabetic dyslipidemia: Molecular characterization and effects of western diet feeding

Kobayashi, Kazuo; Forte, Trudy M.; Taniguchi, Setsuo; Ishida, Brian Y.; Oka, Koichiro; Chan, Lawrence

doi:10.1016/s0026-0495(00)90588-2

Cited by 233 publications

(194 citation statements)

References 49 publications

Supporting

Mentioning

177

Contrasting

Unclassified

Order By: Relevance

“…Similarly, their mean liver cholesterol content after 10 weeks was also significantly higher than that of control mice. The results of these experiments show that dietary cholesterol causes hypercholesterolemia and hepatic steatosis in type 2 diabetes, as previous studies have also demonstrated (13,16). In the animal model, CA showed an inhibitory effect on both conditions when compared with HC-mice which were not given CA.…”

Section: Discussionsupporting

confidence: 84%

“…The occurrence of hyperlipidemia is prevalent in more than 30% of all diabetics, two to three times more frequent than in nondiabetic patients (1). Diabetic dyslipidemia is a major factor contributing to accelerated atherosclerosis (16), while hypercholesterolemia especially is a major risk factor for atherosclerosis and coronary heart disease in type 2 diabetes (9,20). Whole-body cholesterol homeostasis is regulated by de novo synthesis of cholesterol in the liver, dietary cholesterol absorption, and biliary excretion and absorption.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effect of corosolic acid on dietary hypercholesterolemia and hepatic steatosis in KK-Ay diabetic mice

et al. 2010

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 84%

mentioning

confidence: 99%

Effect of corosolic acid on dietary hypercholesterolemia and hepatic steatosis in KK-Ay diabetic mice

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The mice were housed five to ten per polypropylene cage under specific pathogen-free conditions and had free access to the high-energy diet. They developed hyperglycaemia (>11.1 mmol/l) by 12 to 15 weeks of age [24].…”

Section: C57 Bl/ks Lepr Db (Db/db) Micementioning

confidence: 99%

Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes

Anis¹,

Leshem²,

Reuveni³

et al. 2004

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis. G-protein-coupled receptor kinases (GRKs) play a key role in agonist-induced desensitisation of G-protein-coupled receptors (GPCRs) that are involved in metabolic regulation and glucose homeostasis. Our aim was to examine whether small peptides derived from the catalytic domain of GRK2 and -3 would ameliorate Type 2 diabetes in three separate animal models of diabetes. Methods. Synthetic peptides derived from a kinasesubstrate interaction site in GRK2/3 were initially screened for their effect on in vitro melanogenesis, a GRK-mediated process. The most effective peptides were administered intraperitoneally, utilising a variety of dosing regimens, to Psammomys obesus gerbils, Zucker diabetic fatty (ZDF) rats, or db/db mice. The metabolic effects of these peptides were assessed by measuring fasting and fed blood glucose levels and glucose tolerance. Results. Two peptides, KRX-683 107 and KRX-683 124 , significantly reduced fed-state blood glucose levels in the diabetic Psammomys obesus. In animals treated with KRX-683 124 at a dose of 12.5 mg/kg weekly for 7 weeks, ten of eleven treated animals responded with mean blood glucose significantly lower than controls (4.7±0.4 vs 16.8±0.8 mmol/l, p≤0.0001). Significant reductions in blood glucose compared with controls were also seen in ZDF rats administered KRX-683 124 and in db/db mice, which had significantly reduced fasting and 2-hour postprandial glucose levels after the treatment. Conclusions/interpretation. Sequence-based peptides derived from GRK2/3 have an antidiabetic effect demonstrated in three different animal models of Type 2 diabetes. By modulating GRK2/3 activity, these peptides enhance GPCR-initiated signal transduction, resulting in improved glucose homeostasis. Sequencebased peptide modulation of GRK could prove useful in the treatment of Type 2 diabetes.

show abstract

“…Models with construct validity usually, though not invariably (see below), possess some degree of face and predictive validity (Kornetsky and Markowitz 1978;McKinney and Moran 1981;Ellenbroek and Cools 1990;Rupniak and Iversen 1993;Costall and Naylor 1995). A good illustration of valid and useful models of complex diseases are genetic models of diabetes and hypertension; for instance, the db/db mice model of diabetes (Kobayashi et al 2000) and the spontaneously hypertensive rat (SHR) (Patel et al 2000). Unlike these models which faithfully reproduce relatively clear-cut physiological characteristics (e.g., high blood sugar levels or high blood pressure), models of psychiatric disorders face the unique difficulty of simulating much more complex and less easily defined pathophysiology.…”

mentioning

confidence: 99%

To Model a Psychiatric Disorder in Animals Schizophrenia As a Reality Test

Lipska

Weinberger

2000

Neuropsychopharmacology

588

386

View full text Add to dashboard Cite

Animal modeling has been instrumental in dissectingAnimal models are important developments in investigations of the mechanisms underlying a human disease and the design of new treatments. This is true for many diseases, but generally not for mental disorders, whose modeling in experimental animals has often been regarded as a highly controversial or outright heretic idea. An example of a particularly formidable challenge for animal modeling is schizophrenia, a complex disorder of unknown origin, characterized by abnormalities of uniquely human behaviors in the realms of perception, thinking and the experience of emotions, and whose onset is virtually restricted to young adulthood. Schizophrenia is such an inherently human disease that reproducing its most prominent symptoms-hallucinations, delusions and thought disorder-in a rodent or even in a non-human primate seems doomed. However, recent new evidence about the neurobiology of the condition has generated new avenues of animal research. In this perspective article, we highlight recent achievements in the efforts to model the neurobiology of schizophrenia in animals, consider limitations inherent in any heuristic animal model of this and probably other psychiatric disorders, and discuss the usefulness of a new generation of animal models for testing particular hypotheses about etiology and pathophysiology of schizophrenia.

show abstract

The db/db mouse, a model for diabetic dyslipidemia: Molecular characterization and effects of western diet feeding

Cited by 233 publications

References 49 publications

Effect of corosolic acid on dietary hypercholesterolemia and hepatic steatosis in KK-Ay diabetic mice

Effect of corosolic acid on dietary hypercholesterolemia and hepatic steatosis in KK-Ay diabetic mice

Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes

To Model a Psychiatric Disorder in Animals Schizophrenia As a Reality Test

Contact Info

Product

Resources

About