Insulin inhibits glucagon-induced glycogenolysis normally in perivenous hepatocytes of Wistar fatty rats.
Wistar fatty (WF) rats are obese, hyperinsulinemic and hyperglycemic, and thus a model of type 2 diabetes mellitus. Since we have found that insulin specifically inhibits glucagon-induced glycogenolysis in perivenous hepatocytes (PVH) from normal rats, we examined the inhibitory effect of insulin on glucagon-induced glycogenolysis in PVH of hyperinsulinemic WF rats. Basal glucose release was 64.0+/-4.1 nmol/mgprotein/30 min from PVH of lean littermates (WL rats) and 137.0+/-19.3 nmol/mgprotein/30 min from that of WF rats (p<0.01). These were proportional to the glycogen content in PVH of WL and WF rats (56.7+/-7.2 and 131.0+/-20.3 microg/mgprotein, p<0.01), and increased to 109.0+/-8.8 and 225.8+/-17.9nmol/mgprotein/30min, respectively, with 0.1 nmol/l glucagon. When 10 nmol/l insulin was coincubated, 0.1 nmol/l glucagon-induced increase in glucose release decreased to 93.3+/-10.9 nmol/mgprotein/30 min in PVH of WL rats (p<0.01) and to 181+/-20.7 nmol/mgprotein/30 min in PVH of WF rats (p<0.01). Thus, insulin antagonized glucagon-induced glycogenolysis in PVH similarly between WL and WF rats, to 56.7+/-13.3% and to 46.1+/-7.5%, respectively. Thus, the antagonizing effect of insulin on glucagon-induced increase in glycogenolysis was preserved in PVH of hyperinsulinemic and hyperglycemic WF rats.
Ikezawa
Yoshihiro
Y
Third Department of Internal Medicine, Yamagata University School of Medicine, 2-2-2 IidaNishi, Yamagata 990-9585, Japan.
Yamatani
Keiichi
K
Ohnuma
Hiroshi
H
Daimon
Makoto
M
Manaka
Hideo
H
Sasaki
Hideo
H
D000818:Animals; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008112:Liver Glycogen / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D008112:Liver Glycogen; D005934:Glucagon