Hepatic expression of a targeting subunit of protein phosphatase-1 in streptozotocin-diabetic rats reverses hyperglycemia and hyperphagia despite depressed glucokinase expression.

Journal Article

Glycogen-targeting subunits of protein phosphatase-1 (PP-1) are scaffolding proteins that facilitate the regulation of key enzymes of glycogen metabolism by PP-1. In the current study, we have tested the effects of hepatic expression of GMDeltaC, a truncated version of the muscle-targeting subunit isoform, in rats rendered insulin-deficient via injection of a single moderate dose of streptozotocin (STZ). Three key findings emerged. First, GMDeltaC expression in liver was sufficient to fully normalize blood glucose levels (from 335 +/- 31 mg/dl prior to viral injection to 109 +/- 28 mg/dl 6 days after injection) and liver glycogen content in STZ-injected rats. Second, this normalization occurred despite very low levels of liver glucokinase expression in the insulin-deficient STZ-injected rats. Finally, the hyperphagia induced by STZ injection was completely reversed by GMDeltaC expression in liver. In contrast to these findings with GMDeltaC, overexpression of another targeting subunit, GL, in STZ-injected rats caused a large increase in liver glycogen stores but only a transient decrease in food intake and blood glucose levels. The surprising demonstration of a glucose-lowering effect of GMDeltaC in the background of depressed hepatic glucokinase expression suggests that controlled stimulation of liver glycogen storage may be an effective mechanism for improving glucose homeostasis, even when normal pathways of glucose disposal are impaired.

Full Text

Duke Authors

Cited Authors

  • Yang, R; Newgard, CB

Published Date

  • June 27, 2003

Published In

Volume / Issue

  • 278 / 26

Start / End Page

  • 23418 - 23425

PubMed ID

  • 12697773

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M213112200

Language

  • eng

Conference Location

  • United States