Role of glucose, insulin, and glucagon in glycogen mobilization in human hepatocytes.
This study investigated the role of glucose, insulin, and glucagon in the activation of glycogen catabolism in cultured human hepatocytes. Basal glycogenolysis in unstimulated human hepatocytes was low (only 19% of initial glycogen content was degraded in a 4-h incubation) and insensitive to changes in external glucose concentration (from 10 to 0 mM). Both glycogenolysis and glucose output could be significantly stimulated by 35 ng/L glucagon or 10(5) pM dibutyryl cAMP; half-maximal effect was found with 28 x 10(2) ng/L glucagon and 4 x 10(5) pM dibutyryl cAMP. After a 3-h exposure to 35 x 10(3) ng/L glucagon, greater than 90% of glycogen content of human hepatocytes was mobilized. This caused a 4.6-fold increase in the rate of glucose output to the medium compared with nonstimulated cells. About 85% of degraded glycogen rendered glucose to the medium. Insulin (10(4) pM) was able to totally suppress basal glycogenolysis; insulin was also essential to reverse the action of glucagon in hepatocytes incubated with glucagon, whereas glucose alone, even at postprandial concentration, was unable to reverse glucagon action. In summary, these experiments show that the mobilization of glycogen stores of human hepatocytes, as it occurs during the postabsorptive periods in humans, is largely dependent on the presence of glucagon and is not simply due to a decrease of external glucose. Insulin, on the other hand, was essential to suppress both basal and glucagon-activated glycogenolysis.
Pilar López
M
M
Research Center, Hospital La Fe, Valencia, Spain.
Gómez-Lechón
M J
MJ
Castell
J V
JV
D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000494:pharmacology / Q000502:physiology*; D005947:Glucose / Q000502:physiology*; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D007328:Insulin; D003994:Bucladesine; D006003:Glycogen; D005934:Glucagon; D005947:Glucose