Beneficial effect of a chronic treatment with rimonabant on pancreatic function and β-cell morphology in Zucker Fatty rats

Duvivier, Valérie; Delafoy-Plasse, Laure; Delion, Véronique; Lechevalier, Patricia; Bail, Jean-Christophe Le; Guillot, Etienne; Pruniaux, Marie-Pierre; Galzin, Anne-Marie

doi:10.1016/j.ejphar.2009.05.024

Cited by 28 publications

(36 citation statements)

References 34 publications

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“…Moreover, chronic CB1R antagonism improved insulin sensitivity in rats with diet-induced obesity compared to pair-fed and ad libitum-fed controls [32]. Finally, chronic CB1 antagonism treatment of male obese Zucker rats reduced glucose-stimulated insulin secretion, whereas glucose tolerance was unchanged during an oral glucose tolerance test (OGTT) [33]. Chronic CB1R antagonism may improve glucose tolerance through an increased insulin-mediated glucose transport in skeletal muscles, as a 7-day treatment with the CB1R antagonist led to increase in vitro insulin stimulation of glucose transport activity in the soleus muscle of leptin-deficient obese mice [34].…”

Section: Discussionmentioning

confidence: 99%

Effect of CB1-Antagonist (AM251) on Metabolic Syndrome (Prophylactic and Therapeutic)

Alrawashdeh¹,

Ahmed²,

Madi³

et al. 2018

J Drug Metab Toxicol

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The present study was designed to investigate the possible prophylactic and therapeutic effect of cannabinoid receptors type1 (CB1) antagonist (AM251) on fructose-induced metabolic syndrome in rats, through administration of high fructose diet for 12 weeks. Prophylactic treatment by CB1-antagonist (AM251) significantly returned triglyceride, inflammatory, oxidative stress parameters and liver enzymes to the normal values while it significantly improved blood pressure, glucose, insulin, and IR and lipid profile but not significantly returned to the normal values. Interestingly, it significantly decreased body weight to values less than corresponding normal group. Histopathological findings confirmed that CB1-antagonist (AM251) in both prophylactic and therapeutic group improved histopathological changes of the liver and aorta induced by high fructose (60%) diet, with no drug had the upper hand of improvement of these histopathological changes.

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Section: Discussionmentioning

confidence: 99%

Effect of CB1-Antagonist (AM251) on Metabolic Syndrome (Prophylactic and Therapeutic)

Alrawashdeh¹,

Ahmed²,

Madi³

et al. 2018

J Drug Metab Toxicol

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“…No significant difference was observed in the glucose areas under the curve (AUCs); however, the concentration of insulin during the GTT was lower (Fig. 1H) (25) led to similar improvements in insulinemia, glucose tolerance, and ␤-cell rest. KCOs possess a distinct but transient signature effect in the GTT after acute exposure.…”

Section: Chronic Administration Of Rimonabant and Ibipinabant Lead Tomentioning

confidence: 98%

“…Our data suggest a potential lead in this regard; however, we ackowlege that additional work is needed to determine the extent to which a KCO mechanism contributes to chronic improvements in insulinemia with rimonabant and ibipinibant. Although rimonabant, diazoxide, and NN414 treatments have led to similar improvements in insulinemia, pancreatic function, and/or morphology in Zucker rats (1,3,4,6,8,16,25), caution is warranted in interpreting all of the chronic positive effects of rimonabant and ibipinabant on insulinemia as being mediated through direct K ATP channel opening at this time.…”

Section: E547mentioning

confidence: 99%

“…In rodents this was associated with a histomorphological phenomenon termed ␤-cell rest, which is associated with prevention of progression from obesity to diabetes conversion (25). The mechanism by which rimonabant led to improvements in insulinemia and ␤-cell rest has not been determined.…”

mentioning

confidence: 99%

“…improvements in insulinemia, glycemic control, adiponectin, homeostatic model assessment method to quantify insulin resistance (HOMA-IR), atherogenic profile, and cardiovascular risk factors, along with markers of improved ␤-cell function and rest (21,25,61,75,78). Given this potential, in 2006, it was even approved in several countries for, among other indications, obesity and diabetes prevention.…”

mentioning

confidence: 99%

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Some cannabinoid receptor ligands and their distomers are direct-acting openers of SUR1 K_ATP channels

Lynch

Zhou

Show-Ling

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Here, we examined the chronic effects of two cannabinoid receptor-1 (CB1) inverse agonists, rimonabant and ibipinabant, in hyperinsulinemic Zucker rats to determine their chronic effects on insulinemia. Rimonabant and ibipinabant (10 mg·kg−1·day−1) elicited body weight-independent improvements in insulinemia and glycemia during 10 wk of chronic treatment. To elucidate the mechanism of insulin lowering, acute in vivo and in vitro studies were then performed. Surprisingly, chronic treatment was not required for insulin lowering. In acute in vivo and in vitro studies, the CB1 inverse agonists exhibited acute K channel opener (KCO; e.g., diazoxide and NN414)-like effects on glucose tolerance and glucose-stimulated insulin secretion (GSIS) with approximately fivefold better potency than diazoxide. Followup studies implied that these effects were inconsistent with a CB1-mediated mechanism. Thus effects of several CB1 agonists, inverse agonists, and distomers during GTTs or GSIS studies using perifused rat islets were unpredictable from their known CB1 activities. In vivo rimonabant and ibipinabant caused glucose intolerance in CB1 but not SUR1-KO mice. Electrophysiological studies indicated that, compared with diazoxide, 3 μM rimonabant and ibipinabant are partial agonists for K channel opening. Partial agonism was consistent with data from radioligand binding assays designed to detect SUR1 KATP KCOs where rimonabant and ibipinabant allosterically regulated 3H-glibenclamide-specific binding in the presence of MgATP, as did diazoxide and NN414. Our findings indicate that some CB1 ligands may directly bind and allosterically regulate Kir6.2/SUR1 KATP channels like other KCOs. This mechanism appears to be compatible with and may contribute to their acute and chronic effects on GSIS and insulinemia.

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Contribution of Phospholipid, Sphingolipids, and Cholesterol‐Derived Lipid Mediators in the Pathogenesis of Metabolic Syndrome and Neurological Disorders

Farooqui

2013

Metabolic Syndrome and Neurological Disorders

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Beneficial effect of a chronic treatment with rimonabant on pancreatic function and β-cell morphology in Zucker Fatty rats

Cited by 28 publications

References 34 publications

Effect of CB1-Antagonist (AM251) on Metabolic Syndrome (Prophylactic and Therapeutic)

Effect of CB1-Antagonist (AM251) on Metabolic Syndrome (Prophylactic and Therapeutic)

Some cannabinoid receptor ligands and their distomers are direct-acting openers of SUR1 K_ATP channels

Contribution of Phospholipid, Sphingolipids, and Cholesterol‐Derived Lipid Mediators in the Pathogenesis of Metabolic Syndrome and Neurological Disorders

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Beneficial effect of a chronic treatment with rimonabant on pancreatic function and β-cell morphology in Zucker Fatty rats

Cited by 28 publications

References 34 publications

Effect of CB1-Antagonist (AM251) on Metabolic Syndrome (Prophylactic and Therapeutic)

Effect of CB1-Antagonist (AM251) on Metabolic Syndrome (Prophylactic and Therapeutic)

Some cannabinoid receptor ligands and their distomers are direct-acting openers of SUR1 KATP channels

Contribution of Phospholipid, Sphingolipids, and Cholesterol‐Derived Lipid Mediators in the Pathogenesis of Metabolic Syndrome and Neurological Disorders

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Product

Resources

About

Some cannabinoid receptor ligands and their distomers are direct-acting openers of SUR1 K_ATP channels