Psammomys obesus and the albino rat-two different models of nutritional                insulin resistance, representing two different types of human                populations

Kalman, Ronny; Ziv, Ehud; Shafrir, Eleazar; Bar‐On, Hanoch; Pérez, Roald Gómez

doi:10.1258/0023677011911949

Cited by 16 publications

(16 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The nutritionally induced diabetes in Psammomys obesus is analogous to forms of Type 2 diabetes seen in several human population groups such as the Native American Pima Indians and the Australian Aborigines [22]. The course of diabetes in those animals is characterised by an initial stage of hyperinsulinaemia, followed by hyperinsulinaemic hyperglycaemia and a hypoinsulinaemic phase associated with ketosis and ultimate death.…”

Section: Discussionmentioning

confidence: 90%

“…Female Psammomys gerbils were bred at the Hebrew University-Hadassah Medical School Animal Farm and housed in individual polypropylene cages. Animals from the diabetes-prone line [22] were weaned at 3 weeks of age and started on a low-energy diet (2.4 kcal/g, 16.7% protein; Koffolk, Petach Tikva, Israel). Animals were subsequently randomised to a high-energy diet (3.0 kcal/g, 23.4% protein; Tekled Global, Madison, Wis., USA) or kept on the low-energy diet.…”

Section: Animal Models Of Diabetesmentioning

confidence: 99%

See 1 more Smart Citation

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

Anis¹,

Leshem²,

Reuveni³

et al. 2004

Diabetologia

Self Cite

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

Section: Discussionmentioning

confidence: 90%

Section: Animal Models Of Diabetesmentioning

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, both of these animal models develop diabetes rapidly after the initiation of the diabetogenic treatment which makes these models difficult for use in the testing of preventative treatments. Furthermore, despite their polygenic obesity, these animal models still present etiologic disparities such as the need for pharmaceutically induced ␤-cell destruction in the HFD streptozotocintreated rat and the extreme diet sensitivity expressed in the sand rat, with younger animals developing hyperglycemia within 14 days after initiation of a high-energy diet (23).…”

Section: Discussionmentioning

confidence: 99%

Development and characterization of a novel rat model of type 2 diabetes mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat

Cummings

Digitale

Stanhope³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

101

162

View full text Add to dashboard Cite

(T2DM) is increasing, creating a need for T2DM animal models for the study of disease pathogenesis, prevention, and treatment. The purpose of this project was to develop a rat model of T2DM that more closely models the pathophysiology of T2DM in humans. The model was created by crossing obese Sprague-Dawley rats with insulin resistance resulting from polygenic adult-onset obesity with Zucker diabetic fatty-lean rats that have a defect in pancreatic ␤-cell function but normal leptin signaling. We have characterized the model with respect to diabetes incidence; age of onset; longitudinal measurements of glucose, insulin, and lipids; and glucose tolerance. Longitudinal fasting glucose and insulin data demonstrated progressive hyperglycemia (with fasting and fed glucose concentrations Ͼ250 and Ͼ450 mg/dl, respectively) after onset along with hyperinsulinemia resulting from insulin resistance at onset followed by a progressive decline in circulating insulin concentrations, indicative of ␤-cell decompensation. The incidence of diabetes in male and female rats was 92 and 43%, respectively, with an average age of onset of 6 mo in males and 9.5 mo in females. Results from intravenous glucose tolerance tests, pancreas immunohistochemistry, and islet insulin content further support a role for ␤-cell dysfunction in the pathophysiology of T2DM in this model. Diabetic animals also exhibit glycosuria, polyuria, and hyperphagia. Thus diabetes in the UC Davis-T2DM rat is more similar to clinical T2DM in humans than in other existing rat models and provides a useful model for future studies of the pathophysiology, treatment, and prevention of T2DM. diabetic rodent model; hyperglycemia; insulin; ␤-cell TYPE 2 DIABETES MELLITUS (T2DM) is a devastating metabolic disease presently affecting at least 16 million people in the United States alone (33, 49). The prevalence of T2DM is also increasing in children and adolescents (42). With the increasing incidence of T2DM, the identification of preventative measures has become crucial, necessitating the development of effective preclinical models for studying approaches for both diabetes prevention and treatment.The most commonly used rodent models of T2DM include the Zucker diabetic fatty (ZDF) rat, the Otsuka Long Evans Tokushima fatty (OLETF) rat, and the db/db mouse, all of which exhibit obesity-associated insulin resistance and impaired ␤-cell function, resulting in diabetes (5, 25, 38). While these animal models have contributed substantially to understanding the pathophysiology and treatment of T2DM and its complications, the basic mechanisms underlying the pathogenesis of diabetes in these models do not correspond with what occurs in most human patients with T2DM. These differences in etiology are likely to hinder effective translational research.Obesity and insulin resistance in most animal models of T2DM result from monogenic mutations that are rare in human and animal populations and present multiple problems in terms of applying these models to clinical T2DM. For example, mutat...

show abstract

“…Female P. obesus gerbils of the diabetes-prone (DP) line [12,14] , bred at the Animal Facility of the Hebrew University-Hadassah Medical School were used in the experiments, performed according to the regulations of the Institutional Animal Care Committee. Psammomys were housed in polypropylene cages in a room with 12 h light on/light off cycle at 22 ° C and humidity of 55%.…”

Section: Animals and Experimental Protocolmentioning

confidence: 99%

Pregnancy Outcome in the <i>Psammomys obesus</i> Gerbil on Low- and High-Energy Diets

Patlas

Avgil²,

Ziv³

et al. 2006

Neonatology

View full text Add to dashboard Cite

Introduction: Diabetes mellitus (DM) during pregnancy is associated with an increased risk for poor reproduction and a high rate of congenital malformations. The gerbil Psammomys obesus is a unique model for nutritionally induced Type 2 DM (T2DM) that enabled us to study the outcome of uncontrolled T2DM during pregnancy. Methods: Female Psammomys on low-energy (LE) or high energy (HE) diet were studied. The blood glucose levels and weights of pregnant animals were determined. The offspring from the different groups were followed-up to weaning. Results: Most of the HE-diet animals were diabetic (77%). There were no differences in the pregnancy rates in animals on both diets (32.7% in HE vs. 38.3% in LE). Pregnancy of the HE-diet group was longer than the LE-diet group (26.7 vs. 26.1 days), and litter average was reduced (2.7 vs. 3.0). At birth, the offspring of the HE-diet dams weighed less (5.2 vs. 7.2 g) and had smaller crown rump length (4.0 vs. 4.6 cm) These offspring also presented a 1–3 days delay in neuro-developmental parameters (first turn over, hair appearance, eye-opening and response to noise). However, from the fourth week of life they became diabetic, and from the third week they weighed more than the LE offspring. Conclusion: HE-diet caused diabetes, maternal complications and altered reproduction in Psammomys animals. The offspring of diabetic Psammomys presented birth weight and length changes as well as developmental delay.

show abstract

Psammomys obesus and the albino rat-two different models of nutritional insulin resistance, representing two different types of human populations

Cited by 16 publications

References 9 publications

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

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

Development and characterization of a novel rat model of type 2 diabetes mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat

Pregnancy Outcome in the <i>Psammomys obesus</i> Gerbil on Low- and High-Energy Diets

Contact Info

Product

Resources

About