The Protective Effect of Metformin on Rat Pancreatic β Cell Dysfunction Induced by High Glucose or High Free Fatty Acids_West China Medical Journal

Authors：

Department of Endocrinology, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

Keywords：

二甲双胍; 胰岛β细胞; 糖毒性; 脂毒性

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

目的:观察二甲双胍对慢性暴露于高糖和高游离脂肪酸的大鼠离体胰岛细胞胰岛素分泌功能的影响。方法:将大鼠离体胰岛细胞培养于5.5~16.7 mmol/L葡萄糖或5.5 mmol/L软脂酸中48 h,再加入不同浓度二甲双胍(0~5 mg/L)培养24 h。收集各组胰岛细胞,加入5.5~16.7 mmol/L葡萄糖刺激培养1 h。收集培养液,用放免法测定其基础及葡萄糖刺激的胰岛素分泌(GSIS)水平。结果:低糖组(5.5 mmol/L葡萄糖)用不同浓度二甲双胍(0~5 mg/L)处理后的β细胞基础及葡萄糖刺激的胰岛素分泌无显著性差异(P gt;0.05);高糖(16.7 mmol/L葡萄糖)及高脂(0.5 mmol/L棕榈酸)组β细胞基础胰岛素分泌较对照组明显增高(P lt;0.01),GSIS较对照组明显降低(P lt;0.01);用2.5~5 mg/L二甲双胍干预后,高糖及高脂组β细胞基础胰岛素分泌较未治疗组明显降低(P lt;0.01),GSIS较未治疗组明显增高(P lt;0.01)。结论:低糖环境下,二甲双胍对β细胞胰岛素分泌功能无明显影响;慢性高糖及高脂可致β细胞胰岛素分泌功能受损;而2.5~5 mg/L二甲双胍能改善糖脂毒性所致β细胞胰岛素分泌功能异常。提示二甲双胍降糖效果除了其外周作用外,可能对糖脂中毒的β细胞具有直接保护作用。

Citation： WANG Yu,LI Xiujun,WU Yunhong,et al. The Protective Effect of Metformin on Rat Pancreatic β Cell Dysfunction Induced by High Glucose or High Free Fatty Acids. West China Medical Journal, 2009, 24(4): 920-922. doi: Copy

1.	任艳,李秀钧,田浩明,等.成都地区65个糖尿病家系的流行病学调查[J].中华内科杂志,2003,42(7):496-497..
2.	任艳,李秀钧,田浩明,等.线粒体糖尿病家系基因突变的遗传学筛查[J].中华医学遗传杂志,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.	邵建华,高妍,袁振芳,等.游离脂肪酸对基础状态β细胞胰岛素分泌和前胰岛素原mRNA表达的影响[J].北京医科大学学报,1998,30(2):127-130..
15.	邵建华,袁振芳,李长红,等.游离脂肪酸促进基础状态胰岛细胞生长和分泌胰岛素[J].中华内科杂志,1997,36(12):831-832.

1. 任艳,李秀钧,田浩明,等.成都地区65个糖尿病家系的流行病学调查[J].中华内科杂志,2003,42(7):496-497..
2. 任艳,李秀钧,田浩明,等.线粒体糖尿病家系基因突变的遗传学筛查[J].中华医学遗传杂志,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. 邵建华,高妍,袁振芳,等.游离脂肪酸对基础状态β细胞胰岛素分泌和前胰岛素原mRNA表达的影响[J].北京医科大学学报,1998,30(2):127-130..
15. 邵建华,袁振芳,李长红,等.游离脂肪酸促进基础状态胰岛细胞生长和分泌胰岛素[J].中华内科杂志,1997,36(12):831-832.

West China Medical Journal

The Protective Effect of Metformin on Rat Pancreatic β Cell Dysfunction Induced by High Glucose or High Free Fatty Acids

Abstract Full text Figures/Tables Video References Cited by

Format

Content