Glucagon-like peptide-1 inhibits glucagon-induced glycogenolysis in perivenous hepatocytes specifically.
Hepatocytes form the hepatic acinus as a unit of microcirculation. Following the bloodstream, at least two different zones can be discerned: the periportal (PPH) and the perivenous (PVH) zones. Recently, we found that insulin inhibits glucagon-induced glycogenolysis in PVH specifically. We therefore investigated the region-specific functional effects of glucagon-like peptide-1 (GLP-1), which is known to have an insulin-like activity, on glucagon-induced glycogenolysis in isolated PPH and PVH prepared by the digitonin-collagenase method. GLP-1 inhibited 0.1 nM glucagon-induced increase in glucose release from the PVH of fed rats specifically (p < 0.01) and had an additive effect with insulin. Insulin binding did not differ between PPH and PVH of fed rats. GLP-1 did not displace [125I]-glucagon binding to the purified hepatic cell membrane. Thus, it is directly confirmed that GLP-1 has an insulin-like activity in the liver.
Ikezawa
Yoshihiro
Y
The 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; D002469:Cell Separation / Q000379:methods; D004072:Digitonin / Q000737:chemistry; D004357:Drug Synergism; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D005943:Gluconeogenesis / Q000187:drug effects*; D006503:Hepatic Veins / Q000166:cytology; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008112:Liver Glycogen / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D003012:Microbial Collagenase / Q000737:chemistry; D008833:Microcirculation / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D008112:Liver Glycogen; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D003012:Microbial Collagenase; D004072:Digitonin