Novel CB1 receptor antagonist BAR-1 modifies pancreatic islet function and clinical parameters in prediabetic and diabetic mice.

Nutrition & Diabetes
Lesly Nava-MolinaAlonso Vilches-Flores

Abstract

Cannabinoid receptor antagonists have been suggested as a novel treatment for obesity and diabetes. We have developed a synthetic cannabinoid receptor antagonist denominated BAR-1. As the function and integrity of a β-cell cellular structure are important keys for diabetes onset, we evaluated the effects of pharmacological administration of BAR-1 on prediabetic and diabetic rodents. CD-1 mice fed a hypercaloric diet or treated with streptozotocin were treated with 10 mg/kg BAR-1 for 2, 4 or 8 weeks. Body weight, oral glucose tolerance test, HbA1c, triglycerides and insulin in serum were measured. In isolated islets, we evaluated stimulated secretion and mRNA expression, and relative area of islets in fixed pancreases. Docking analysis of BAR-1 was complemented. BAR-1 treatment slowed down weight gain in prediabetic mice. Fasting glucose-insulin relation also decreased in BAR-1-treated mice and glucose-stimulated insulin secretion was increased in isolated islets, without effects in oral test. Diabetic mice treated with BAR-1 showed a reduced glucose and a partial recovery of islet integrity. Gene expression of insulin and glucagon showed biphasic behaviour, increasing after 4 weeks of BAR-1 administration; however, after 8 week...Continue Reading

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Citations

Oct 23, 2020·Current Hypertension Reports·Carmen NavarreteEduardo Muñoz
Mar 18, 2021·European Biophysics Journal : EBJ·Anna SobiepanekTomasz Kobiela

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Methods Mentioned

BETA
PCR
enzyme-linked immunosorbent assay
ELISA
reverse-transcription PCR

Software Mentioned

AutoDock Tools
Gaussian
ScopeImage
Linux
AutoDock4
Visual Molecular Dynamics programme ( VMD
Discovery studio
GaussView

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