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Protective Role of Glucagon-like Peptide-1 Against Glucosamine-induced Cytotoxicity in Pancreatic Beta Cells

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Author(s)
Yu-Kyung KimJae-Hyung ParkSung-Hee ParkBora LimWon-Ki BaekSung-Il SuhJung-Geun LimGyeong Ryul RyuDae-Kyu Song
Keimyung Author(s)
Park, Jae HyungSong, Dae KyuBaek, Won KiSuh, Seong IlLim, Jeong Geun
Department
Dept. of Physiology (생리학)
Dept. of Microbiology (미생물학)
Dept. of Neurology (신경과학)
Journal Title
Cellular Physiology and Biochemistry
Issued Date
2010
Volume
25
Issue
2-3
Abstract
High doses of glucosamine have been known to induce apoptosis of pancreatic beta cells. The mechanism for this phenomenon has not been clearly elucidated. We aimed to explore the potential mechanisms for glucosamine toxicity in the rat insulinoma cell line INS-1 and in rat native beta cells. We also investigated whether glucagon-like peptide (GLP)-1 could be protective against glucosamine. Glucosamine exhibited dose-dependent inhibition of cell survival and an increase in the cell population at the sub-G1 phase. Glucosamine was revealed to inhibit cellular glucose uptake, resulting in the activation of AMP-activated protein kinase (AMPK). Accordingly, phosphorylation of P70S6K and ribosomal protein S6 (S6RP) was decreased. Protein glycosylation appeared not to be involved in this cytotoxicity. Pretreatment with GLP-1 alleviated glucosamine-mediated inhibition of glucose uptake and lessened AMPK activation, thus allowing recovery of the phosphorylation levels of P70S6K and S6RP. The effect of GLP-1 was blocked by the adenylyl cyclase inhibitor MDL12330A but not by the protein kinase A inhibitor H89. Taken together, these data demonstrate that glucosamine may inhibit beta-cell survival by diminishing cellular glucose uptake independent of glycosylation. This glucosamine toxicity can be blocked by GLP-1, which leads to recovery of the glucose uptake through a PKA-independent, cAMP-dependent mechanism.
Keimyung Author(s)(Kor)
박재형
송대규
백원기
서성일
임정근
Publisher
School of Medicine
Citation
Yu-Kyung Kim et al. (2010). Protective Role of Glucagon-like Peptide-1 Against Glucosamine-induced Cytotoxicity in Pancreatic Beta Cells. Cellular Physiology and Biochemistry, 25(2–3), 211–220. doi: 10.1159/000276555
Type
Article
ISSN
1015-8987
Source
https://www.karger.com/Article/Abstract/276555
DOI
10.1159/000276555
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35386
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. School of Medicine (의과대학) > Dept. of Neurology (신경과학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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