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

Title
Protective Role of Glucagon-like Peptide-1 Against Glucosamine-induced Cytotoxicity in Pancreatic Beta Cells
Authors
Yu-Kyung KimJae-Hyung ParkSung-Hee ParkBora LimWon-Ki BaekSung-Il SuhJung-Geun LimGyeong Ryul RyuDae-Kyu Song
Keimyung Author(s)
박재형; 송대규; 백원기; 서성일; 임정근
Department
Dept. of Physiology (생리학); Dept. of Microbiology (미생물학); Dept. of Neurology (신경과학); Chronic Disease Research Center (만성질환연구센터)
Keywords
Glucosamine toxicity; Glucagon-like peptide 1; AMP-activated protein kinase; Glucose uptake; Pancreatic beta cell
Issue Date
2010
Publisher
School of Medicine
Citation
Cellular Physiology and Biochemistry, Vol.25(2-3) : 211-220, 2010
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.
URI
http://www.karger.com/Article/Pdf/276555http://kumel.medlib.dsmc.or.kr/handle/2015.oak/17047
ISSN
1015-8987
Appears in Collections:
1. 연구논문 > 1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
1. 연구논문 > 1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. 연구논문 > 1. School of Medicine (의과대학) > Dept. of Neurology (신경과학)
1. 연구논문 > 3. Researcher Institutues (부설연구소) > Chronic Disease Research Center (만성질환연구센터)
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