S15261, A NOVEL AGENT FOR THE TREATMENT OF INSULIN RESISTANCE. STUDIES ON PSAMMOMYS OBESUS

Life Sciences ◽  
1997 ◽  
Vol 61 (18) ◽  
pp. 1741-1753 ◽  
Author(s):  
G Marquié ◽  
T El Madani ◽  
M.L Solera ◽  
J Duhault ◽  
J Espinal ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Psammomys Obesus ◽  
Novel Agent

scholarly journals Intestinal and hepatic cholesterol transporters in Psammomys Obesus, a model of insulin resistance and type 2 diabetes

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Genevieve Lalonde ◽  
Edgard Delvin ◽  
Mounib Elchebly ◽  
Alain Theophile Sane ◽  
Marie Lambert ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Psammomys Obesus ◽  
Hepatic Cholesterol ◽  
Cholesterol Transporters

Increased hepatic lipogenesis in insulin resistance and Type 2 diabetes is associated with AMPK signalling pathway up-regulation in Psammomys obesus

2009 ◽  
Vol 29 (5) ◽  
pp. 283-292 ◽  
Author(s):  
Ali Ben Djoudi Ouadda ◽  
Emile Levy ◽  
Ehud Ziv ◽  
Geneviève Lalonde ◽  
Alain T. Sané ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Protein Expression ◽  
Body Weight Gain ◽  
Binding Protein ◽  
Regulatory Element ◽  
Mrna Levels ◽  
Psammomys Obesus ◽  
Element Binding Protein

AMPK (AMP-activated protein kinase) has been suggested to be a central player regulating FA (fatty acid) metabolism through its ability to regulate ACC (acetyl-CoA carboxylase) activity. Nevertheless, its involvement in insulin resistance- and TD2 (Type 2 diabetes)-associated dyslipidaemia remains enigmatic. In the present study, we employed the Psammomys obesus gerbil, a well-established model of insulin resistance and TD2, in order to appreciate the contribution of the AMPK/ACC pathway to the abnormal hepatic lipid synthesis and increased lipid accumulation in the liver. Our investigation provided evidence that the development of insulin resistance/diabetic state in P. obesus is accompanied by (i) body weight gain and hyperlipidaemia; (ii) elevations of hepatic ACC-Ser79 phosphorylation and ACC protein levels; (iii) a rise in the gene expression of cytosolic ACC1 concomitant with invariable mitochondrial ACC2; (iv) an increase in hepatic AMPKα-Thr172 phosphorylation and protein expression without any modification in the calculated ratio of phospho-AMPKα to total AMPKα; (v) a stimulation in ACC activity despite increased AMPKα phosphorylation and protein expression; and (vi) a trend of increase in mRNA levels of key lipogenic enzymes [SCD-1 (stearoyl-CoA desaturase-1), mGPAT (mitochondrial isoform of glycerol-3-phosphate acyltransferase) and FAS (FA synthase)] and transcription factors [SREBP-1 (sterol-regulatory-element-binding protein-1) and ChREBP (carbohydrate responsive element-binding protein)]. Altogether, our findings suggest that up-regulation of the AMPK pathway seems to be a natural response in order to reduce lipid metabolism abnormalities, thus supporting the role of AMPK as a promising target for the treatment of TD2-associated dyslipidaemia.

Changing pattern of prevalence of insulin resistance in Psammomys obesus, a model of nutritionally induced type 2 diabetes

Metabolism ◽  
1999 ◽  
Vol 48 (12) ◽  
pp. 1549-1554 ◽  
Author(s):  
Ehud Ziv ◽  
Eleazar Shafrir ◽  
Rony Kalman ◽  
Susy Galer ◽  
Hanoch Bar-On
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Psammomys Obesus

scholarly journals A hypercaloric diet induces hepatic oxidative stress, infiltration of lymphocytes, and mitochondrial reshuffle in Psammomys obesus, a murine model of insulin resistance

2019 ◽  
Vol 342 (5-6) ◽  
pp. 209-219 ◽  
Author(s):  
Ouahiba Sihali-Beloui ◽  
Djamila Aroune ◽  
Fella Benazouz ◽  
Adile Hadji ◽  
Salima El-Aoufi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Murine Model ◽  
Psammomys Obesus ◽  
Hepatic Oxidative Stress ◽  
Hypercaloric Diet

Vascular responses to α-adrenergic stimulation and depolarization are enhanced in insulin-resistant and diabetic Psammomys obesus

2003 ◽  
Vol 81 (7) ◽  
pp. 704-710 ◽  
Author(s):  
M Zoltowska ◽  
J St-Louis ◽  
E Ziv ◽  
B Sicotte ◽  
E E Delvin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vascular Reactivity ◽  
Vascular Complications ◽  
Psammomys Obesus ◽  
Adrenergic Stimulation ◽  
Endothelial Lining ◽  
Insulin Resistant ◽  
Group A ◽  
Group B ◽  
Endothelium Dependent Relaxation

Since vascular complications often accompany diabetes, we examined the influence of the endothelial lining on vascular reactivity in Psammomys obesus, a desert gerbil that acquires insulin resistance and diabetes when exposed to a laboratory diet. Vasoconstriction to phenylephrine and depolarizing KCl, as well as carbachol endothelium-dependent relaxation, were assessed in rings of thoracic aortae obtained from three groups: (i) group A, normoglycemic–normoinsulinemic; (ii) group B, normoglycemic–hyperinsulinemic, and (iii) group C, hyperglycemic–hyperinsulinemic animals. As expected, marked hypertriglyceridemia and hypercholesterolemia characterized groups B and C, which developed enhanced contractile responsiveness to phenylephrine and KCl compared with controls (group A). Furthermore, both experimental groups displayed a significant decrease in endothelium-dependent relaxation to carbachol. Altered lipid profiles are considered to play some role in the observed modification of aortic reactivity. Overall, our data indicate that vascular contractile responsiveness is enhanced early in the development of insulin resistance and diabetes in the female P. obesus.Key words: insulin resistance, diabetes, vascular reactivity, LDL-cholesterol, hypertriglyceridemia.

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

2001 ◽  
Vol 35 (4) ◽  
pp. 346-352 ◽  
Author(s):  
R. Kalman ◽  
E. Ziv ◽  
E. Shafrir ◽  
H. Bar-On ◽  
R. Perez
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Body Weight ◽  
High Energy ◽  
Low Energy ◽  
Albino Rats ◽  
Human Populations ◽  
Psammomys Obesus ◽  
Pima Indians

Animal models for insulin resistance and type 2 diabetes are required for the study of the mechanism of these phenomena and for a better understanding of diabetes complications in human populations. Type 2 diabetes is a syndrome that affects 5-10% of the adult population. Hyperinsulinaemia, hypertriglyceridaemia, decreased high-density lipoprotein (HDL) cholesterol levels, obesity and hypertension, all form a cluster of risk factors that increase the risk of coronary artery disease, and are known as insulin resistance syndrome or syndrome X. The gerbil, Psammomys obesus is characterized by primary insulin resistance and is a well-defined model for dietary induced type 2 diabetes. Weanling Psammomys and Albino rats were held individually for several weeks on high energy (HE) and low energy (LE) diets in order to determine the development of metabolic changes leading to diabetes. Feeding Psammomys on HE diet resulted in hyperglycaemia (303 ± 40 mg/dl), hyperinsulinaemia (194 ± 31 µU/ml) and a moderate elevation in body weight, obesity and plasma triglycerides. Albino rats on HE diet demonstrated an elevation in plasma insulin (30 ± 4 µU/ml), hypertriglyceridaemia (170 µ 11 mg/dl), an elevation in body weight and obesity, but maintained normoglycaemia (98 µ 6 mg/dl). Psammomys represent a model that is similar to human populations, with primary insulin resistance expressed in young age, which leads to a high percentage of adult type 2 diabetes. Examples for such populations are the Pima Indians, Australian Aborigines and many other Third World populations. The results indicate that the metabolism of Psammomys is well adapted towards life in a low energy environment, where Psammomys takes advantage of its capacity for a constant accumulation of adipose tissue that will serve for maintenance and breeding in periods of scarcity. This metabolism known as 'thrifty metabolism', is compromised at a high nutrient intake.

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