| First Author | Ali ES | Year | 2021 |
| Journal | Am J Physiol Cell Physiol | Volume | 321 |
| Issue | 1 | Pages | C187-C198 |
| PubMed ID | 34106786 | Mgi Jnum | J:312202 |
| Mgi Id | MGI:6720714 | Doi | 10.1152/ajpcell.00020.2021 |
| Citation | Ali ES, et al. (2021) Impaired Ca(2+) signaling due to hepatic steatosis mediates hepatic insulin resistance in Alstrom syndrome mice that is reversed by GLP-1 analog treatment. Am J Physiol Cell Physiol 321(1):C187-C198 |
| abstractText | Ca(2+) signaling plays a critical role in the regulation of hepatic metabolism by hormones including insulin. Changes in cytoplasmic Ca(2+) regulate synthesis and posttranslational modification of key signaling proteins in the insulin pathways. Emerging evidence suggests that hepatocyte intracellular Ca(2+) signaling is altered in lipid-loaded liver cells isolated from obese rodent models. The mechanisms of altered Ca(2+)-insulin and insulin-Ca(2+) signaling pathways in obesity remain poorly understood. Here, we show that the kinetics of insulin-initiated intracellular (initial) Ca(2+) release from endoplasmic reticulum is significantly impaired in steatotic hepatocytes from obese Alstrom syndrome mice. Furthermore, exenatide, a glucagon-like peptide-1 (GLP-1) analog, reversed lipid-induced inhibition of intracellular Ca(2+) release kinetics in steatotic hepatocytes, without affecting the total content of intracellular Ca(2+) released. Exenatide reversed the lipid-induced inhibition of intracellular Ca(2+) release, at least partially, via lipid reduction in hepatocytes, which then restored hormone-regulated cytoplasmic Ca(2+) signaling and insulin sensitivity. This data provides additional evidence for the important role of Ca(2+) 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. |
