Angiotensin II Modulates Podocyte Glucose Transport

Abstract

Podocytes play a central role in the maintenance of the glomerular filtration barrier and are cellular targets of angiotensin II (AngII). Non-hemodynamic pathways of AngII signaling regulate cellular function and mediate podocyte abnormalities that are associated with various glomerulopathies, including diabetic kidney disease. In this study we investigated the capacity of AngII to modulate glucose uptake in mouse podocytes expressing the human AT1 receptor (AT1R+) after 5 days of exposure to normal (NG, 5.6 mmol/L) or to high (HG, 30 mmol/L) glucose. Short (30 min) as well as long-term (24 h) incubations with AngII markedly enhanced glucose transport in both NG and HG cells. In podocytes cultured under NG conditions, AngII inhibited insulin-stimulated glucose uptake. Regardless of the presence or absence of AngII, no effect of insulin on glucose uptake was observed in HG cells. Stimulation of glucose transport by AngII was mediated by protein kinase C and by phosphoinositide 3-kinase. Glucose dependent surface expression of the glucose transporters GLUT1, GLUT2, and GLUT4 was modulated by AngII in a time and glucose concentration dependent manner. Furthermore, despite its inhibitory effect on insulin's action, AngII elevated the number of podocyte insulin receptors in both NG and HG cultured cells. These findings demonstrate that AngII modulates podocyte basal, as well as insulin-dependent glucose uptake by regulating glucose transporters and insulin signaling.

Ketamine ameliorates depressive-like behaviors in mice through increasing glucose uptake regulated by the ERK/GLUT3 signaling pathway

“…Relevant studies have shown that GLUTs play a key role in the glucose uptake of astrocytes 30 , among which GLUT1, GLUT3, and GLUT4 play important roles 31 . Hence, in the current study, we detected the expression levels of GLUT1, GLUT3, and GLUT4 induced by ketamine in astrocytes.…”

One Molecule for Mental Nourishment and More: Glucose Transporter Type 1—Biology and Deficiency Syndrome

“…As Glut1 predominates in mesangial cells, as well as in podocytes, Glut1 activity alterations are deleterious in diabetic nephropathy, stimulating renal extracellular matrix production the most [ 87 , 88 ]. The GLUT1 Enh2 genetic variation, located within a binding site for the insulin-responsive transcription factor, is associated with albuminuria, matrix expansion and glomerulosclerosis [ 88 ].…”

“…The GLUT1 Enh2 genetic variation, located within a binding site for the insulin-responsive transcription factor, is associated with albuminuria, matrix expansion and glomerulosclerosis [ 88 ]. Podocytes enhance their glucose uptake but decrease their GLUT1 expression when exposed to mechanical stress, suggesting alternative glucose transporters during stress/injury [ 87 , 89 ].…”

Human Glucose Transporters in Renal Glucose Homeostasis

“…GLUT4 is expressed in the glomerulus [27], and in the mesangial cells and podocytes. Animal studies indicate that GLUT1, GLUT2, and GLUT4 expression in podocytes is modulated by angiotensin II [28]. The presence of the GLUT4 mRNA and protein were detected in the thick ascending limb of the loop of Henle (TAL), and it has been suggested that GLUT4 may be involved in managing the local resources in this segment [24].…”