Review article: role of glucagon-like peptide-1 receptor agonists in non-alcoholic steatohepatitis, obesity and diabetes-what hepatologists need to know.

Background: Non-alcoholic steatohepatitis (NASH) is characterised by hepatic lipid accumulation, cell injury, inflammation and fibrosis. Insulin resistance, a hallmark of type 2 diabetes (T2D) and obesity, is a key pathogenic driver of NASH. Other than difficult-to-maintain lifestyle changes, there are no approved treatments for NASH.

Abrogation of insulin-like growth factor-I (IGF-I) and insulin action by mevalonic acid depletion: synergy between protein prenylation and receptor glycosylation pathways.

The vasculoprotective effects of hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors (statins) correlate with cholesterol lowering. HMG-CoA reductase inhibitors also disrupt cellular processes by the depletion of isoprenoids and dolichol. Insulin and insulin-like growth factor (IGF) signaling appear particularly prone to such disruption as intracellular receptor processing requires dolichol for correct N-glycosylation, whereas downstream signaling through Ras requires the appropriate prenylation (farnesol).

Caspase-mediated Cleavage of Insulin Receptor Substrate.

Apoptosis is an important mechanism for maintaining tissue homeostasis. The efficient induction and execution of apoptosis are essential for cell clearance in specific developmental situations. Insulin-like growth factor (IGF)-I is a survival factor for epithelial cells in the mammary gland, and its withdrawal or inhibition leads to apoptosis.

Insulin-like growth factor binding protein 5 and apoptosis in mammary epithelial cells.

Insulin-like growth factors (IGFs) are important survival signals that can protect a range of cell types from apoptosis. Although IGF bioavailability is modulated by high affinity interactions with IGF-binding proteins (IGFBPs), there is currently no experimental evidence that IGFBPs regulate the survival function of IGFs in the mammary gland. We have examined IGFBP expression during mammary gland development and studied the effects of IGFBPs on IGF-mediated survival and signalling in mammary epithelial cells in culture.

Insulin-like growth factors and insulin-like growth factor binding proteins in mammary gland function.

Insulin-like growth factor (IGF)-mediated proliferation and survival are essential for normal development in the mammary gland during puberty and pregnancy. IGFs interact with IGF-binding proteins and regulate their function. The present review focuses on the role of IGFs and IGF-binding proteins in the mammary gland and describes how modulation of their actions occurs by association with hormones, other growth factors and the extracellular matrix.

Cell-matrix interactions during development and apoptosis of the mouse mammary gland in vivo.

Epithelial cell survival is dependent on extracellular signals provided by both soluble factors and by adhesion. In the mammary gland, extensive apoptosis of epithelial cells occurs rapidly when lactation ceases, but the mechanism of apoptosis induction is not known. In tissue culture, mammary epithelial cells require laminin as a survival ligand and specific beta1 integrins are necessary to suppress apoptosis.

The intestinal epithelial stem cell.

This article considers the role of the adult epithelial stem cell, with particular reference to the intestinal epithelial stem cell. Although the potential of adult stem cells has been revealed in a number of recent publications, the organization and control of the stem cell hierarchy in epithelial tissues is still not fully understood. The intestinal epithelium is an excellent model in which to study such hierarchies, having a distinctive polarity and high rate of cell proliferation and migration.