Dataset Information

Comparative Analysis of CTRP-Mediated Effects on Cardiomyocyte Glucose Metabolism: Cross Talk between AMPK and Akt Signaling Pathway.

ABSTRACT: C1q/tumor necrosis factor -alpha-related proteins (CTRPs) have been shown to mediate protective cardiovascular effects, but no data exists on their effects on glucose and fatty acid (FA) metabolism in cardiomyocytes. In the present study, adult rat cardiomyocytes and H9C2 cardiomyoblasts were stimulated with various recombinant CTRPs. Glucose or FA uptake, expression of genes involved in glucose or FA metabolism and the role of the AMP-activated protein kinase (AMPK) and Akt were investigated. Although most CTRPs induced an increase in phosphorylation of AMPK and Akt in cardiomyocytes, mainly CTRP2, 7, 9 and 13 induced GLUT1 and GLUT4 translocation and glucose uptake in cardiomyocytes, despite high structural similarities among CTRPs. AMPK inhibition reduced the CTRPs-mediated activation of Akt, while Akt inhibition did not impair AMPK activation. In addition, CTRP2, 7, 9 and 13 mediated strong effects on the expression of enzymes involved in glucose or FA metabolism. Loss of adiponectin receptor 1, which has been suggested to be involved in CTRP-induced signal transduction, abolished the effects of some but not all CTRPs on glucose metabolism. Targeting the AMPK signaling pathway via CTRPs may offer a therapeutic principle to restore glucose homeostasis by acting on glucose uptake independent of the Akt pathway.

SUBMITTER: Li L

PROVIDER: S-EPMC8070942 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundA positive association between diabetes and breast cancer has been identified by various epidemiological and clinical studies. However, the possible molecular interactions between the two heterogeneous diseases have not been fully determined yet. There are several underlying mechanisms which may increase the risk of breast cancer in diabetic patients.IntroductionIn this study, we focused on the role of O-GlcNAc transferase (OGT) enzyme in the regulation of phosphatidylinositol-3 kinase (PI3K) pathway through activation/deactivation of Akt protein. The efficiency of insulin signaling in adipocytes is reduced as a result of OGT overexpression which further attenuates Akt signaling; as a result, the efficiency of insulin signaling is reduced by downregulation of insulin-responsive genes. On the other hand, increased expression of OGT results in Akt activation in breast cancer cells, leading to enhanced cell proliferation and inhibition of the apoptosis. However, the interplay amongst these signaling pathways is still under investigation.MethodsIn this study, we used Petri nets (PNs) to model and investigate the role of PI3K and OGT pathways, acting as key players in crosstalk between diabetes and breast cancer, resulting in progression of these chronic diseases. Moreover, in silico perturbation experiments were applied on the model to analyze the effects of anti-cancer agents (shRNA and BZX) and anti-diabetic drug (Metformin) on the system.ResultsOur PN model reflects the alterations in protein expression and behavior and the correlation between breast cancer and diabetes. The analysis proposed two combination therapies to combat breast cancer progression in diabetic patients including combination of OGTmRNA silencing and OGT inhibitor (BZX) as first combination and BZX and Metformin as the second.ConclusionThe PN model verified that alterations in O-GlcNAc signaling affect both insulin resistance and breast cancer. Moreover, the combination therapy for breast cancer patients consisting of anti-diabetic drugs such as Metformin along with OGT inhibitors, for example BZX, can produce better treatment regimens.

Dataset Information

Comparative Analysis of CTRP-Mediated Effects on Cardiomyocyte Glucose Metabolism: Cross Talk between AMPK and Akt Signaling Pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure