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Updated: Sep 27, 2026

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Glucagon-like peptide-1 inhibits glucagon-induced glycogenolysis in perivenous hepatocytes specifically
Yoshihiro Ikezawa1, Keiichi Yamatani, Hiroshi Ohnuma
1The Third Department of Internal Medicine, Yamagata University School of Medicine, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
Abstract:
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.
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