二甲雙胍對糖脂中毒的大鼠胰島β細胞胰島素分泌功能的保護作用_《華西醫學》

作者：

四川大學華西醫院內分泌科,四川成都 610041;

關鍵詞：

二甲雙胍胰島β細胞糖毒性脂毒性

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目的:觀察二甲雙胍對慢性暴露于高糖和高游離脂肪酸的大鼠離體胰島細胞胰島素分泌功能的影響。方法:將大鼠離體胰島細胞培養于5.5~16.7 mmol/L葡萄糖或5.5 mmol/L軟脂酸中48 h,再加入不同濃度二甲雙胍(0~5 mg/L)培養24 h。收集各組胰島細胞,加入5.5~16.7 mmol/L葡萄糖刺激培養1 h。收集培養液,用放免法測定其基礎及葡萄糖刺激的胰島素分泌(GSIS)水平。結果:低糖組(5.5 mmol/L葡萄糖)用不同濃度二甲雙胍(0~5 mg/L)處理后的β細胞基礎及葡萄糖刺激的胰島素分泌無顯著性差異(P gt;0.05);高糖(16.7 mmol/L葡萄糖)及高脂(0.5 mmol/L棕櫚酸)組β細胞基礎胰島素分泌較對照組明顯增高(P lt;0.01),GSIS較對照組明顯降低(P lt;0.01);用2.5~5 mg/L二甲雙胍干預后,高糖及高脂組β細胞基礎胰島素分泌較未治療組明顯降低(P lt;0.01),GSIS較未治療組明顯增高(P lt;0.01)。結論:低糖環境下,二甲雙胍對β細胞胰島素分泌功能無明顯影響;慢性高糖及高脂可致β細胞胰島素分泌功能受損;而2.5~5 mg/L二甲雙胍能改善糖脂毒性所致β細胞胰島素分泌功能異常。提示二甲雙胍降糖效果除了其外周作用外,可能對糖脂中毒的β細胞具有直接保護作用。

引用本文： 王煜,李秀鈞,鄔云紅,童南偉,趙鐵耘,李潔,趙桂芝. 二甲雙胍對糖脂中毒的大鼠胰島β細胞胰島素分泌功能的保護作用. 華西醫學, 2009, 24(4): 920-922. doi: 復制

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14.	邵建華,高妍,袁振芳,等.游離脂肪酸對基礎狀態β細胞胰島素分泌和前胰島素原mRNA表達的影響[J].北京醫科大學學報,1998,30(2):127-130..
15.	邵建華,袁振芳,李長紅,等.游離脂肪酸促進基礎狀態胰島細胞生長和分泌胰島素[J].中華內科雜志,1997,36(12):831-832.

1. 任艷,李秀鈞,田浩明,等.成都地區65個糖尿病家系的流行病學調查[J].中華內科雜志,2003,42(7):496-497..
2. 任艷,李秀鈞,田浩明,等.線粒體糖尿病家系基因突變的遺傳學篩查[J].中華醫學遺傳雜志,2003,9(3):181-185..
3. MCGARRY J D. Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes[J]. Diabetes,2002,51(1):7-18..
4. CUSI K, DEFRONZO R A. Metformin:a review of its metabolic effects[J]. Diabetes Rev,1998,6:89..
5. PATANE G, PIRO S, RABUAZZO A M, et al. Metformin restores insulin secretion altered by chroni exposure to free fatty acids o high glucose: a direct metformin effect on pancreatic β-cell[J]. Diabetes,2000,49:7350..
6. PIERO MARCHETTI, SILVIA D G, LORELLA M, et al. Pancreatic islets from type 2 diabetes patients have functional defects and increased apoptosis that are ameliorated by metformin[J]. J Clin Endocrinol,2004,89:5535-5541..
7. LUPI R, DEL GUERRA S, TELLINI C, et al. The biguanide compound metformin prevents desensitization of human pancreatic islets induced by high glucose[J]. Eur J Pharmacol,1999,364(2-3):205-209..
8. KNUDSEN P, KOFOD H, LERNMARK A, et al. L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase[J]. Am J Physiol,1983,245(4):E338-E346..
9. NIELSEN J H, MANDRUP-POULSEN T, NERUP J. Direct effects of cyclosporin A on human pancreatic β-cells[J]. Diabetes,1986,35(9):1049-1052.〖ZK)〗.
10. BOYD AE 3RD. Sulfonylurea receptors, ion channels, and fruit flies[J]. Diabetes,1988,37(7):847-850..
11. LUPI R, MARCHETTI P, GIANNARELLI R, et al. Effects of glibenclamide and metformin (alone or in combination) on insulin release from isolated human pancreatic islets[J]. Acta Diabetol,1997,34(1):46-48..
12. BODEN G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM[J]. Diabetes,1997,46:3-10..
13. YOSHIKAWA H, TAJIRI Y, SAKO Y, et al. Effect of free fatty acids on β cell functions: a possible involvement of peroxisome proliferatoractivated receptors α or pancreatic/duodenal homeobox[J]. Metabolism,2001,50:613-618..
14. 邵建華,高妍,袁振芳,等.游離脂肪酸對基礎狀態β細胞胰島素分泌和前胰島素原mRNA表達的影響[J].北京醫科大學學報,1998,30(2):127-130..
15. 邵建華,袁振芳,李長紅,等.游離脂肪酸促進基礎狀態胰島細胞生長和分泌胰島素[J].中華內科雜志,1997,36(12):831-832.

《華西醫學》

二甲雙胍對糖脂中毒的大鼠胰島β細胞胰島素分泌功能的保護作用

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《華西醫學》

二甲雙胍對糖脂中毒的大鼠胰島β細胞胰島素分泌功能的保護作用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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