Prevention of nutritionally induced diabetes by rosiglitazone in the gerbil Psammomys obesus

Hefetz, Simona; Ziv, Ehud; Jörns, Anne; Lenzen, Sigurd; Shafrir, Eleazar

doi:10.1002/dmrr.583

Cited by 9 publications

(4 citation statements)

References 42 publications

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“…Hefetz and colleagues also reported no change in the total lipid content in skeletal muscle from diabetic P. obesus following rosiglitazone treatment, although they did not examine the size distribution of the lipid droplets [40]. Interestingly, microscopy analysis of pancreatic sections revealed that rosiglitazone prevented the decrease in insulin immunostaining induced by the high energy diet and accelerated β-cell proliferation (measured by BrdU incorporation into nuclei) [40]. Based on these observations, Hefetz et al concluded that the major anti-diabetic action of rosiglitazone in P. obesus was by preventing the deterioration of pancreatic function.…”

Section: Discussionmentioning

confidence: 99%

“…Here we provide evidence to suggest that rosiglitazone treatment results in a reduction in lipid droplet size in skeletal muscle without a significant change in total IMCL. Hefetz and colleagues also reported no change in the total lipid content in skeletal muscle from diabetic P. obesus following rosiglitazone treatment, although they did not examine the size distribution of the lipid droplets [40]. Interestingly, microscopy analysis of pancreatic sections revealed that rosiglitazone prevented the decrease in insulin immunostaining induced by the high energy diet and accelerated β-cell proliferation (measured by BrdU incorporation into nuclei) [40].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of rosiglitazone on intramyocellular lipid accumulation in Psammomys obesus

Molero

Lee

Leizerman³

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of rosiglitazone on intramyocellular lipid accumulation in Psammomys obesus

Molero

Lee

Leizerman³

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Glucose metabolism in peripheral tissues was not the primary target of the beneficial effect of rosiglitazone, but rosiglitazone prevented the damage to pancreatic ␤-cells and loss of insulin, thus enabling insulin secretion to compensate for the peripheral insulin resistance (Hefetz et al 2006). Marquie and coworkers (1997) studied the oral agent S15261 (3-[2-[2-[4-[2-[␣-fluorenyl acetyl amino ethyl] enzoylosy] ethyl amino]1-methoxy ethyl] trifluoromethylbenzene), which also prevented the ␤-cell lesion in the HE diet-maintained Psammomys.…”

Section: Psammomys As a Model For Testing Antihyperglycemic Drugsmentioning

confidence: 98%

Nutritionally Induced Diabetes in Desert Rodents as Models of Type 2 Diabetes: Acomys cahirinus (Spiny Mice) and Psammomys obesus (Desert Gerbil)

Shafrir

Ziv²,

Kalman³

2006

ILAR Journal

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The dietary effects of hyperglycemia increasingly result in type 2 diabetes in humans. Two species, the spiny mice (Acomys cahirinus) and the desert gerbil (Psammomys obesus), which have different metabolic responses to such effects, are discussed. Spiny mice exemplify a pathway that leads to diabetes without marked insulin resistance due to low supply of insulin on abundant nutrition, possibly characteristic of a desert animal. They respond with obesity and glucose intolerance, beta-cell hyperplasia, and hypertrophy on a standard rodent diet supplemented with fat-rich seeds. The accompanying hyperglycemia and hyperinsulinemia are mild and intermittent but after a few months, the enlarged pancreatic islets suddenly collapse, resulting in loss of insulin and ketosis. Glucose and other secretagogues produce only limited insulin release in vivo and in vitro, pointing to the inherent disability of the beta-cells to respond with proper insulin secretion despite their ample insulin content. On a 50% sucrose diet there is marked lipogenesis with hyperlipidemia without obesity or diabetes, although beta-cell hypertrophy is evident. P.obesus is characterized by muscle insulin resistance and the inability of insulin to activate the insulin signaling on a high-energy (HE) diet. Insulin resistance imposes a vicious cycle of Hyperglycemia and compensatory hyperinsulinemia, leading to beta-cell failure and increased secretion of proinsulin. Ultrastructural studies reveal gradual disappearance of beta-cell glucokinase, GLUT 2 transporter, and insulin, followed by apoptosis of beta-cells. Studies using the non-insulin-resistant HE diet-fed animals maintained as a control group are discussed. The insulin resistance that is evident to date in the normoglycemic state on a low-energy diet indicates sparing of glucose fuel in muscles of a desert-adapted animal for the benefit of glucose obligatory tissues. Also discussed are the effect of Psammomys age on the disabetogenicity of the HE diet; the impaired function of several components of the insulin signal transduction pathway in muscles, which reduces the availability of GLUT4 transporter; the testing of several antidiabetic modalities for the prevention of nutritional diabetes in Psammomys; and various complications related to the diabetic condition.

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“…Another mechanism that might be involved in our study is based on the anti-oxidative activity of CBD [13,23], that very likely prevents beta cell destruction in the HE fed Psammomys. Vanadyl sulfate and rosiglitazone have also been found to be effective in preventing hyperglycemia and hyperinsulinemia [24,25], while nicotine treatment [26] caused decrease in food intake and body weight. An antidiabetic effect was also obtained by G protein kinase analogs [27] and electroacupuncture [28].…”

Section: Open Accessmentioning

confidence: 99%

Islet protection and amelioration of diabetes type 2 in Psammomys obesus by treatment with cannabidiol

Ziv¹,

Weiss²,

Patlas

et al. 2012

JDM

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Background and purpose: Cannabidiol (CBD), a non-psychoactive component of Cannabis sativa, has been shown by us, to have an anti-inflammatory effect in collagen-induced arthritis in DBA mice and in type 1 diabetes in NOD mice. As inflammation is a process involved in diabetes type 2, we administered CBD to Psammomys obesus (sand rats), a species which develops diabetes type 2 when fed high-energy (HE) diet, to investigate whether we can hinder the development of the disease. Experimental Approach: Male Psammomys obesus were kept on a high energy diet during the experiments. They were treated with CBD (i.p injection, 5 mg/kg, 5 times/week) for 4 weeks and kept (without CBD) for another 29 - 39 days. The weights of the animals as well as blood glucose and plasma insulin levels were determined and the morphology of the pancreatic islets was examined. Key results: CBD significantly reduced blood glucose levels in Psammomys obesus, without effecting body weight. Plasma insulin levels were significantly higher in the CBD-treated group. The most striking effect noted was the marked decrease of the destruction of pancreatic islets and beta cells. Conclusions and implications: CBD partially protects pancreatic islets and beta cells from destruction. CBD lowers significantly the blood glucose level and increases insulin level in Psammomys obesus with diabetes type 2, but does not lead to obesity. As CBD already has been administered to patients for other medical indications we propose its use as a therapeutic agent in diabetes type 2

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Prevention of nutritionally induced diabetes by rosiglitazone in the gerbil Psammomys obesus

Cited by 9 publications

References 42 publications

Effects of rosiglitazone on intramyocellular lipid accumulation in Psammomys obesus

Effects of rosiglitazone on intramyocellular lipid accumulation in Psammomys obesus

Nutritionally Induced Diabetes in Desert Rodents as Models of Type 2 Diabetes: Acomys cahirinus (Spiny Mice) and Psammomys obesus (Desert Gerbil)

Islet protection and amelioration of diabetes type 2 in <i>Psammomys obesus</i> by treatment with cannabidiol

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Prevention of nutritionally induced diabetes by rosiglitazone in the gerbil Psammomys obesus

Cited by 9 publications

References 42 publications

Effects of rosiglitazone on intramyocellular lipid accumulation in Psammomys obesus

Effects of rosiglitazone on intramyocellular lipid accumulation in Psammomys obesus

Nutritionally Induced Diabetes in Desert Rodents as Models of Type 2 Diabetes: Acomys cahirinus (Spiny Mice) and Psammomys obesus (Desert Gerbil)

Islet protection and amelioration of diabetes type 2 in &lt;i&gt;Psammomys obesus&lt;/i&gt; by treatment with cannabidiol

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Islet protection and amelioration of diabetes type 2 in <i>Psammomys obesus</i> by treatment with cannabidiol