MAD2-Dependent Insulin Receptor Endocytosis Regulates Metabolic Homeostasis

Diabetes, Journal Year: 2023, Volume and Issue: 72(12), P. 1781 - 1794

Published: Sept. 19, 2023

Insulin activates insulin receptor (IR) signaling and subsequently triggers IR endocytosis to attenuate signaling. Cell division regulators MAD2, BUBR1, p31comet promote on stimulation. Here, we show that genetic ablation of the IR-MAD2 interaction in mice delays endocytosis, increases levels, prolongs action at cell surface. This turn causes a defect clearance circulating unexpectedly increasing glucagon which alters glucose metabolism modestly. Disruption serum fatty acid concentrations hepatic fat accumulation fasted male mice. Furthermore, disruption distinctly changes metabolic transcriptomic profiles liver adipose tissues. Our findings establish function provide insights into functions endocytosis.

Language: Английский

---

Role of Oxidative Stress and Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in Nonalcoholic Fatty Liver Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11271 - 11271

Published: July 10, 2023

Nonalcoholic fatty liver disease (NAFLD) has become a widely studied subject due to its increasing prevalence and links diseases such as type 2 diabetes obesity. It severe complications, including nonalcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, portal hypertension that can lead transplantation in some cases. To better prevent treat this pathology, it is important understand underlying physiology. Here, we identify two main factors play crucial role the pathophysiology of NAFLD: oxidative stress key carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). We discuss linking these NAFLD pathophysiology.

Language: Английский

---

Intact ketogenesis predicted reduced risk of moderate-severe metabolic-associated fatty liver disease assessed by liver transient elastography in newly diagnosed type 2 diabetes

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Hepatic ketogenesis is a key metabolic pathway that regulates energy homeostasis. Some related controversies exist regarding the pathogenesis of metabolic-associated fatty liver disease (MAFLD). We aimed to investigate whether intact ketogenic capacity could reduce risk MAFLD based on transient electrography (TE) in patients with newly diagnosed type 2 diabetes (T2D).

Language: Английский

---

Cell-specific regulation of insulin action and hepatic fibrosis by CEACAM1

Metabolism and Target Organ Damage, Journal Year: 2024, Volume and Issue: 4(4)

Published: Sept. 26, 2024

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has reached an epidemic rise worldwide. is a constellation broad range and histopathologic abnormalities. It begins with hepatic steatosis progresses to steatohepatitis (MASH), including fibrosis, apoptosis, cell injury. Despite ample research effort, the pathogenesis not been fully delineated. Whereas insulin resistance implicated in early stages disease, its role fibrosis remains controversial. We have focused our studies on carcinoembryonic antigen-related adhesion molecule 1 (CEACAM1) hepatocytes endothelial cells histopathological dysregulation MASH. Patients MASH exhibit lower CEACAM1 progressive decline as stage advances. In mice, conditional deletion impairs clearance cause hyperinsulinemia-driven even when mice are fed regular chow diet. contrast, causes inflammation-driven without adversely affecting metabolism (mice remain insulin-sensitive do develop steatosis). Thus, this review provides vivo evidence that supports or discards injury fibrosis.

Language: Английский

---

Involvement of a battery of investigated genes in lipid droplet pathophysiology and associated comorbidities

Adipocyte, Journal Year: 2024, Volume and Issue: 13(1)

Published: Sept. 27, 2024

Lipid droplets (LDs) are highly specialized energy storage organelles involved in the maintenance of lipid homoeostasis by regulating flux within white adipose tissue (WAT). The physiological function adipocytes and LDs can be compromised mutations several genes, leading to NEFA-induced lipotoxicity, which ultimately manifests as metabolic complications, predominantly form dyslipidemia, ectopic fat accumulation, insulin resistance. In this review, we delineate effects deficiencies genes -

Language: Английский

---