Open AccessRelationship of Glycogen Synthase and Glycogen Phosphorylase to Protein Phosphatase 2C and cAMP‐Dependent Protein Kinase in Liver of Obese Rhesus Monkeys
Author(s) -
Ortmeyer H. K.
Publication year - 1997
Publication title -
obesity research
Language(s) - English
Resource type - Journals
eISSN - 1550-8528
pISSN - 1071-7323
DOI - 10.1002/j.1550-8528.1997.tb00583.x
Subject(s) - medicine , glycogen phosphorylase , endocrinology , glycogen synthase , basal (medicine) , glycogen , gsk 3 , phosphatase , enzyme assay , protein kinase a , dephosphorylation , enzyme , kinase , chemistry , diabetes mellitus , biochemistry
Abstract ORTMEYER HK. Relationship of glycogen synthase and glycogen phosphorylase to protein phosphatase 2C and cAMP‐dependent protein kinase in liver of obese rhesus monkeys. The regulation of glycogen synthase (GS) and glycogen phosphorylase (GP) activity by phosphorylation/ dephosphorylation has been proposed to be via changes in activities of several different protein (serine/ threonine) phosphatases and kinases, including protein phosphatase (PP) 1/2A, PP2C, and cAMP‐dependent protein kinase (PKA). In order to determine whether PP1/2A, PP2C, and/or PKA activities are related to GS and/or GP activities, these enzymes were measured in freeze‐clamped liver biopsies obtained under basal fasting conditions from 16 obese monkeys. Four monkeys were normoglycemic and normoinsulinemic, five were hyperinsulinemic, and seven had type 2 diabetes (NIDDM). Liver glycogen and glucose 6‐phosphate (G6P) contents were also determined. Basal enzyme activities and basal substrate concentrations were not significantly different between the three groups of obese monkeys; however, there were several significant linear relationships observed when the monkeys were treated as one group. Therefore, multiple regression was used to determine the correlation between key variables. GS fractional activity was correlated to GP fractional activity ( p <0. 05) and to PP2C activity (p=0. 005) (adjusted R 2 ,53%). GP independent activity was correlated to GS independent activity ( p <0. 07) and to PKA fractional activity ( p =0. 005) (adjusted R 2 ,64%). PP2C activity was correlated to GS fractional activity ( p <0. 0005) and to PP1/2A activity G7<0. 0001) (adjusted R 2 ,83%). PKA fractional activity was correlated to GP total activity ( p <0. 0005) and to age ( p =0. 001) (adjusted R2 82%). G6P content was correlated to glycogen content ( p <0. 05) and to PP2C activity ( p =0. 0005) (adjusted R 2 ,73%). In conclusion, PP2C and PKA are involved in the regulation of GS and GP activity in the basal state in liver of obese monkeys with a wide range of glucose tolerance.