Glucagon stimulates phosphorylation of different peptides in isolated periportal and perivenous hepatocytes

Abstract

The perivenous and periportal zones of the liver acinus differ in enzyme complements and capacities for gluconeogenesis, glycolysis and other metabolic processes. The biochemical factors governing this metabolic zonation are still poorly understood. Glueagon-mediated protein phosphorylation is an important factor in the regulation of hepatic metabolism. Here we show, by comparing the 32P-lahelling pattern of isolated periportal and perivenous hepatocytes, that glucagon promotes the phosphorylation of zone-specific peptides as well as three common peptides (glycogen phosphorylase, glycogen synthase and pyruvate kinase) in the two cell types. We propose that the zone-specific phosphorylation of peptides is an important factor governing the shortterm zonation of metabolic processes in the liver.

Glucagon, cyclic AMP, and hepatic glucose mobilization: A half‐century of uncertainty

“…Effects produced by concentrations above 100 pM are mediated by the activation of both the PLC/IP3 and AC/cAMP pathways simultaneously. The data are adapted from Aggarwal et al (1995), Ekdahl and Ekman (1987), Fleig et al (1984), Marks and Parker Botelho, (1986) and Staddon and Hansford (1989). See also El‐Maghrabi et al (1982), Felíu et al (1976), Ikezawa et al (1998) and Studer et al (1984).…”

“…Glycogen synthase (GS) is a promiscuous target. It can be phosphorylated and inhibited not only by PKA or CaMK, but also by PhosK, PKC, and glycogen synthase kinase, among others (Aggarwal et al, 1995; Camici et al, 1984; Ciudad et al, 1984; Imazu et al, 1984; Juhl et al, 1983; Marks & Parker Botelho, 1986; Rothermel et al, 1984; Staddon & Hansford, 1989; Wang et al, 1986).…”

“…. (1976),El-Maghrabi et al (1982), Felíu et al (1976 ↑ GS phosphorylation 1Aggarwal et al (1995) ↓ GS activity 6Marks and Parker Botelho (1986) andRothermel, Jastor, et al (1984) …”