Insulin Resistance Induced by Loop Diuretics and Hyperosmolarity in Perfused Rat Liver
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Freimut Schliess
, Stephan vom Dahl and Dieter Häussinger
Abstract
Insulininduced cell swelling was recently suggested to reflect an independent signal for metabolic insulin effects such as inhibition of hepatic proteolysis, which is transmitted at the level of autophagosome formation via p38 activation [Häussinger et al., Gastroenterology 116 (1999), 921 935]. Here, the role of insulininduced cell swelling in the overall context of insulin signalling towards proteolysis inhibition was studied in perfused rat liver. Loop diuretics and hyperosmolarity, which impair insulinstimulated cell swelling, strongly blunt Erk-2 and p38 activation as well as proteolysis inhibition by insulin, but are without effect on insulininduced tyrosine phosphorylation of IRβ and IRS-1. Inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) also block insulininduced cell swelling, MAP kinase activation and proteolysis inhibition, but the antiproteolytic response to hypoosmolarity remains unaffected. We suggest that PI3-kinasemediated cell swelling induced by insulin is required to amplify the insulin signal to MAP kinases and thus proteolysis regulation. The perturbation of insulininduced cell swelling may be of pathophysiological relevance for the development of insulin resistance in clinical situations associated with hyperosmotic dehydration and loop diuretic treatment.
Copyright © 2001 by Walter de Gruyter GmbH & Co. KG
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- Functional Genomics in HIV-1 Virus Replication: Protein-Protein Interactions as a Basis for Recruiting the Host Cell Machinery for Viral Propagation
- On the Characterization of the Putative S20-Thx Operon of Thermus thermophilus
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