Ca2+ entry through SOCs (store-operated Ca2+ channels; SOCE) is substantially inhibited in steatotic liver cells through a mechanism involving protein kinase C (PKC). Inhibition of Ca2+ entry enhances...

Yousuf A. Khan (YAK) Lab - Studying RNA folding, interactions, and cellular effects using Molecular and Cellular Physiology, Structural Biology, and Machine Learning at Stanford University

Ribonucleotide reductase subunit M2-mediated dGTP and dCTP production promotes resistance to standard-of-care chemotherapy in GBM.

Ca2+ signaling plays a critical role in the regulation of hepatic metabolism by hormones including insulin. Changes in cytoplasmic Ca2+ regulate synthesis and posttranslational modification of key signaling proteins in the insulin pathways. Emerging evidence suggests that hepatocyte intracellular Ca2+ signaling is altered in lipid-loaded liver cells isolated from obese rodent models. The mechanisms of altered Ca2+-insulin and insulin-Ca2+ signaling pathways in obesity remain poorly understood. Here, we show that the kinetics of insulin-initiated intracellular (initial) Ca2+ release from endoplasmic reticulum is significantly impaired in steatotic hepatocytes from obese Alström syndrome mice. Furthermore, exenatide, a glucagon-like peptide-1 (GLP-1) analog, reversed lipid-induced inhibition of intracellular Ca2+ release kinetics in steatotic hepatocytes, without affecting the total content of intracellular Ca2+ released. Exenatide reversed the lipid-induced inhibition of intracellular Ca2+ release, at least partially, via lipid reduction in hepatocytes, which then restored hormone-regulated cytoplasmic Ca2+ signaling and insulin sensitivity. This data provides additional evidence for the important role of Ca2+ signaling pathways in obesity-associated impaired hepatic lipid homeostasis and insulin signaling. It also highlights a potential advantage of GLP-1 analogs when used to treat type 2 diabetes associated with hepatic steatosis.

Hepatic steatosis, the first step in nonalcoholic fatty liver disease (NAFLD), can arise from various pathophysiological conditions. While lipid metabolism in the liver is normally balanced such that ...

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths in men, and the sixth in women. Non-alcoholic fatty liver disease …

Hepatic steatosis, the first step in nonalcoholic fatty liver disease (NAFLD), can arise from various pathophysiological conditions. While lipid metabolism in the liver is normally balanced such that ...

Hepatic steatosis, the first step in nonalcoholic fatty liver disease (NAFLD), can arise from various pathophysiological conditions. While lipid metabolism in the liver is normally balanced such that ...

Nucleotides are the fundamental building blocks for the preservation of life. As monomeric units, purine and pyrimidine nucleotides are polymerized into RNA and DNA. Mammalian cells require extracellu...

Costas Lyssiotis, Ph.D., co-director of the Rogel and Blondy Center for Pancreatic Cancer at the Rogel Cancer Center, was one of six researchers to receive inaugural grants from the Stephenson Global ...

People living with type 1 diabetes have significantly increased cardiovascular risk compared with the general population. Traditional risk factors include hypertension, dyslipidaemia, and obesity. How...

Shan et al. demonstrate that itaconate promotes proinflammatory cytokine production and NLRP3 inflammasome activation in alveolar macrophages, contrasting its anti-inflammatory role in BMDMs. Itaconat...

Mitochondrial ROS is necessary for the release of a critical anti-inflammatory cytokine.

Mitochondria are metabolic hubs that communicate with other organelles via metabolite-, lipid-, and signaling-molecule exchange facilitated by membrane contact sites (MCSs). MCSs, regulated by tetheri...

Mitochondria are metabolic hubs that communicate with other organelles via metabolite-, lipid-, and signaling-molecule exchange facilitated by membrane contact sites (MCSs). MCSs, regulated by tetheri...

Nucleoside metabolism regulates immune cell development and function, but the therapeutic implications of this link have yet to be fully realized. Evidence f...

SLC35B1, initially thought to be a nucleotide sugar transporter, is an essential ATP/ADP exchanger that imports ATP into the endoplasmic reticulum through a unique stepwise translocation mechanism.

Lysosomal phospholipase PLA2G15 was identified as a physiological BMP hydrolase whose activity depends on unique esterification and stereochemistry of BMP and offers a potential therapeutic targe...

Redox regulators are emerging as critical mediators of lung tumorigenesis. NRF2 and its negative regulator KEAP1 are commonly mutated in human lung ca…