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Background: Proinflammatory cytokines are one of the causes of diabetes mellitus. However, the exact molecular mechanism by which proinflammatory cytokines induce β-cell death remains to be clearly elucidated. Glucagon-like peptide-1 (GLP-1) affects the stimulation of insulin secretion and the preservation of β-cells. Additionally, it may exert an antiapoptotic effect on β cells; however,the mechanism underlying this effect has yet to be demonstrated. Therefore, we investigated the protective effects of GLP-1 in endoplasmic reticulum (ER)-mediated β-cell apoptosis using proinflammatory cytokines. Methods: To induce ER stress, hamster insulin-secreting tumor (HIT)-T15 cells were treated using a mixture of cytokines. Apoptosis was evaluated via MTT assay, Hoechst 33342 staining, and annexin/propidium iodide (PI) flow cytometry. The mRNA and protein expression levels of ER stress-related molecules were determined via PCR and Western blotting, respectively. Nitric oxide was measured with Griess reagent. The levels of inducible nitric oxide synthase (iNOS) mRNA and protein were analyzed via real-time PCR and Western blot, respectively. iNOS protein degradation was evaluated via immunoprecipitation. We pretreated HIT-T15 cells with exendin (Ex)-4 for 1 hour prior to the induction of stress. Results: We determined that Ex-4 exerted a protective effect through nitric oxide and the modulation of ER stress-related molecules (glucose-regulated protein [GRP]78, GRP94, and CCAAT/enhancer-binding protein homologous protein [CHOP]) and that Ex-4stimulates iNOS protein degradation via the ubiquitination pathway. Additionally, Ex-4 also induced the recovery of insulin2 mRNA expression in β cells. Conclusion: The results of this study indicate that GLP-1 may protect β cells against apoptosis through the ubiquitination pathway.

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기사명 저자명 페이지 원문 목차
Current understanding and treatment of primary hyperparathyroidism John I. Lew pp.109-117

No Significance of the Free Cortisol Index Compared to Total Cortisol in Critically Ill Patients Doo-Man Kim pp.118-119

No significance of the free cortisol index compared to total cortisol in critically ill patients Kyung Won Kim, Sang Wan Kim, Hee Joung Kim, Chan Soo Shin, Sung Jae Park, Gil Joon Suh, Seong Yeon Kim pp.120-125

제2형 당뇨병과 대장암과의 연관성 이병도, 배영필, 김봉건, 박종화, 김동현, 박자영, 최성호, 박희승, 이재승, 이창원, 김상수, 김보현, 최문기, 김인주 pp.126-132

Prevalence and characteristics of metabolically obese but normal weight and metabolically healthy but obese in middle-aged Koreans : the Chungju Metabolic disease Cohort(CMC) study Seung-Hwan Lee, Hee-Sung Ha, Young-Jun Park, Jin-Hee Lee, Hyeon-Woo Yim, Kun-Ho Yoon, Moo-Il Kang, Won-Chul Lee, Ho-Young Son, Yong-Moon Park, Hyuk-Sang Kwon pp.133-141

전염증성 사이토카인에 의해 유도된 베타세포 자연사에 대한 유비퀴틴화를 통한 GLP-1의 보호효과 임동미, 김주영, 이강우, 박근용, 김병준 pp.142-149

다발성 압박 골절을 동반한 임신 후 척추 골다공증 1예 이지은, 장진선, 고선희, 김민희, 임동준, 강무일, 차봉연, 홍숙희, 배자성, 류경식 pp.150-154

기립성저혈압으로 인한 실신으로 발현된 갈색세포종 1예 김지연, 김성우, 이승준, 김현숙, 정의달, 금윤섭 pp.155-159

(A)case of pituitary adenoma with simultaneous secretion of TSH and GH Eun Young Lee, Cheol Ryong Ku, Hyun Min Kim, Woo Kyoung Lee, Jung Soo Lim, Sena Hwang, Do Hwan Kim, Dong Yeob Shin, Eun Jig Lee pp.160-165

초음파와 Sestamibi 주사에 보이지 않았던 부갑상선 선종에 의한 원발성 부갑상선 기능항진증 1예 오경용, 최병호, 이유경, 김도환, 이현승, 김광준, 이시훈, 임승길 pp.166-170

새로운 MEN1 유전자 돌연변이가 증명된 가족성 제1형 다발내분비종양 1예 김민정, 김은희, 신미선, 김주희, 나희경, 박성준, 이상아, 고은희, 이우제, 송기호, 박중열, 이기업, 김구환, 유한욱, 김민선 pp.171-176

Mutational analysis of the NF1 gene in two families with neurofibromatosis 1 accompanied by pheochromocytoma Hyon-Seung Yi, Sei Hyun Kim, Jihoon Kim, Eun-Jin Bae, Suntaek Hong, Ie Byung Park, Yu Jin Kim, Sihoon Lee pp.177-184

참고문헌 (13건) : 자료제공( 네이버학술정보 )

참고문헌 목록에 대한 테이블로 번호, 참고문헌, 국회도서관 소장유무로 구성되어 있습니다.
번호 참고문헌 국회도서관 소장유무
1 Diabetes and Suppressors of Cytokine Signaling Proteins 네이버 미소장
2 Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. 네이버 미소장
3 Kaufman RJ, Scheuner D, Schroder M, Shen X, Lee K, Liu CY, Arnold SM: The unfolded protein response in nutrient sensing and differentiation. Nat Rev Mol Cell Biol 3:411-421, 2002 미소장
4 Protective Effects of Glucagon Like Peptide-1 on HIT-T15 beta Cell Apoptosis via ER Stress Induced by 2-deoxy-D-glucose 소장
5 Interleukin-1 plus gamma-interferon-induced pancreatic beta-cell dysfunction is mediated by beta-cell nitric oxide production. 네이버 미소장
6 Cytokine-mediated induction of anti-apoptotic genes that are linked to nuclear factor kappa-B (NF-κB) signalling in human islets and in a mouse beta cell line 네이버 미소장
7 Free fatty acids and cytokines induce pancreatic beta-cell apoptosis by different mechanisms: role of nuclear factor-kappaB and endoplasmic reticulum stress. 네이버 미소장
8 Anti-inflammatory action of exendin-4 in human islets is enhanced by phosphodiesterase inhibitors: potential therapeutic benefits in diabetic patients 네이버 미소장
9 Identification of novel cytokine-induced genes in pancreatic beta-cells by high-density oligonucleotide arrays. 네이버 미소장
10 Inflammatory cytokine signaling in insulin producing beta-cells enhances the colocalization correlation coefficient between L-type voltage-dependent calcium channel and calcium-sensing receptor. 네이버 미소장
11 TNF-alpha and IFN-gamma potentiate the deleterious effects of IL-1 beta on mouse pancreatic islets mainly via generation of nitric oxide. 네이버 미소장
12 Kang JH, Chang SY, Jang HJ, Kim DB, Ryu GR, Ko SH, Jeong IK, Jo YH, Kim MJ: Exendin-4 inhibits interleukin-1beta-induced iNOS expression at the protein level, but not at the transcriptional and posttranscriptional levels, in RINm5F beta-cells. J Endocrinol 202:65-75, 2009 미소장
13 Themes and variations on ubiquitylation. 네이버 미소장

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