Kidney Proximal Tubule GLUT2-More than Meets the Eye.

Tubulopathy plays a central role in the pathophysiology of diabetic kidney disease (DKD). Under diabetic conditions, the kidney proximal tubule cells (KPTCs) are exposed to an extensive amount of nutrients, most notably glucose; these nutrients deteriorate KPTCs function and promote the development and progression of DKD. Recently, the facilitative glucose transporter 2 (GLUT2) in KPTCs has emerged as a central regulator in the pathogenesis of DKD.

Opposite physiological and pathological mTORC1-mediated roles of the CB1 receptor in regulating renal tubular function.

Activation of the cannabinoid-1 receptor (CBR) and the mammalian target of rapamycin complex 1 (mTORC1) in the renal proximal tubular cells (RPTCs) contributes to the development of diabetic kidney disease (DKD). However, the CBR/mTORC1 signaling axis in the kidney has not been described yet. We show here that hyperglycemia-induced endocannabinoid/CBR stimulation increased mTORC1 activity, enhancing the transcription of the facilitative glucose transporter 2 (GLUT2) and leading to the development of DKD in mice; this effect was ameliorated by specific RPTCs ablation of GLUT2.

Effects of Environmental Heat Load on Endocannabinoid System Components in Adipose Tissue of High Yielding Dairy Cows.

Environmental heat load (HL) adversely affects the performance of dairy cows. The endocannabinoid system (ECS) regulates metabolism and the stress response, thus we hypothesized that HL may affect the ECS of dairy cows. Our objective was to determine the levels of endocannabinoids (eCBs) and gene and protein expressions of the ECS components in adipose tissue (AT) and plasma of early postpartum (PP) and late-lactation cows.

Dual inhibition of cannabinoid CB receptor and inducible NOS attenuates obesity-induced chronic kidney disease.

Background And Purpose: Obesity, an important risk factor for developing chronic kidney disease (CKD), affects the kidneys by two main molecular signalling pathways: the endocannabinoid/CB receptor system, whose activation in obesity promotes renal inflammation, fibrosis, and injury, and the inducible NOS (iNOS), which generates ROS resulting in oxidative stress. Hence, a compound that inhibits both peripheral CB receptors and iNOS may serve as an effective therapeutic agent against obesity-induced CKD.

Experimental Approach: Here, we describe the effect of a novel peripherally restricted, orally bioavailable dual CB receptor/iNOS antagonist, MRI-1867 (3 mg·kg ), in ameliorating obesity-induced CKD, and compared its metabolic and renal efficacies to a stand-alone peripheral CB receptor antagonist (JD5037; 3 mg·kg ), iNOS antagonist (1400W; 10 mg·kg ), and pair feeding.