• 西安交通大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院普外科(陜西西安 710061);

目的  研究胃袖帶切除術(shù)(sleeve gastrectomy,SG)對GK大鼠2型糖尿?。╰ype 2 diabetes mellitus,T2DM)的治療作用及其可能機理。
方法  將13只12周齡的GK大鼠隨機分為2組:SG組7只和假手術(shù)組(SO組) 6只,分別行SG術(shù)和假手術(shù)。于術(shù)前及術(shù)后1、4、10和26周測量2組大鼠的體質(zhì)量、24h進(jìn)食量、空腹血糖值、血清胰高血糖素樣肽-1 (glucagon-like peptide-1,GLP-1)和血清生長激素釋放肽(Ghrelin)濃度;于術(shù)后10周檢測2組大鼠的糞便能量含量,并進(jìn)行口服葡萄糖耐量實驗(OGTT)和胰島素耐受性實驗(ITT)。
結(jié)果 ?、袤w質(zhì)量:各時點2組大鼠的體質(zhì)量比較差異均無統(tǒng)計學(xué)意義(P>0.05);與術(shù)前比較,術(shù)后1周2組大鼠的體質(zhì)量均降低
(P<0.01),術(shù)后10和26周的體質(zhì)量均增加(P<0.01)。②24h進(jìn)食量:與SO組比較,術(shù)后4和10周SG組大鼠的24h進(jìn)食量均較低(P<0.05)。與術(shù)前比較,SG組大鼠術(shù)后1、4及10周的進(jìn)食量均較低(P<0.05),SO組大鼠術(shù)后1周的進(jìn)食量低于術(shù)前(P<0.05)。③空腹血糖值:與SO組比較,術(shù)后各時點SG組大鼠的空腹血糖值均較低(P<0.01)。與術(shù)前比較,SG組大鼠術(shù)后各時點的空腹血糖值均較低(P<0.01),而SO組大鼠僅術(shù)后1周明顯低于術(shù)前(P<0.01)。④血清GLP-1水平:與SO組比較,術(shù)后4、10及26周SG組大鼠的血清GLP-1水平均較高(P<0.05)。與術(shù)前比較,術(shù)后4、10及26周SG組大鼠的血清GLP-1水平較高(P<0.05),而術(shù)后SO組大鼠的血清GLP-1水平無明顯變化(P>0.05)。⑤血清Ghrelin水平:與SO組比較,術(shù)后各時點SG組大鼠的血清Ghrelin水平均較低(P<0.01)。與術(shù)前比較,術(shù)后各時點SG組大鼠的血清Ghrelin水平均較低(P<0.001),而SO組大鼠的血清Ghrelin水平無明顯變化(P>0.05)。⑥曲線下面積(AUC):SG組大鼠的AUC (OGTT和ITT)均較SO組低(P<0.01)。
結(jié)論  SG術(shù)可以明顯降低GK大鼠的空腹血糖值,改善葡萄糖耐量及增強胰島素敏感性,該作用可能是GLP-1、Grelin等多種胃腸道激素共同作用的結(jié)果。SG術(shù)可能是潛在的非肥胖型T2DM的治療方法。

引用本文: 張仕運,孫學(xué)軍,鄭見寶,王煒,劉棟,陳南征,賀賽,周培華,王孝瓏. 胃袖帶切除術(shù)對GK大鼠2型糖尿病的影響及其機理△. 中國普外基礎(chǔ)與臨床雜志, 2013, 20(12): 1363-1368. doi: 復(fù)制

1. Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus:a review of current trends[J]. Oman Med J, 2012, 27(4):269-273.
2. Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus[J]. Ann Surg, 1995, 222(3):339-350.
3. Salehi M, Prigeon RL, D’Alessio DA. Gastric bypass surgery enhances glucagon-like peptide 1-stimulated postprandial insulin secretion in humans[J]. Diabetes, 2011, 60(9):2308-2314.
4. Ramos AC, Galvão Neto MP, de Souza YM, et al. Laparoscopic duodenal-jejunal exclusion in the treatment of type 2 diabetes mellitus in patients with BMI<30 kg/m2 (LBMI)[J]. Obes Surg, 2009, 19(3):307-312.
5. Lemanu DP, Srinivasa S, Singh PP, et al. Laparoscopic sleeve gastrectomy:its place in bariatric surgery for the severely obese patient[J]. N Z Med J, 2012, 125(1359):41-49.
6. Galli J, Li LS, Glaser A, et al. Genetic analysis of non-insulin dependent diabetes mellitus in the GK rat[J]. Nat Genet, 1996, 12(1):31-37.
7. Li F, Zhang G, Liang J, et al. Sleeve gastrectomy provides a bettercontrol of diabetes by decreasing ghrelin in the diabetic Goto-Kakizaki rats[J]. J Gastrointest Surg, 2009, 13(12):2302-2308.
8. de Bona Castelan J, Bettiol J, d’Acampora AJ, et al. Sleeve gastrectomy model in Wistar rats[J]. Obes Surg, 2007, 17(7):957-961.
9. Pruessner JC, Kirschbaum C, Meinlschmid G, et al. Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change[J]. Psychoneuroendocrinology, 2003, 28(7):916-931.
10. Pata G, Crea N, Di Betta E, et al. Biliopancreatic diversion with transient gastroplasty and duodenal Switch:long-term results of a multicentric study[J]. Surgery, 2013, 153(3):413-422.
11. 張曉娟, 杜涓, 杜瀟, 等. 腹腔鏡下胃轉(zhuǎn)流術(shù)治療肥胖型2型糖尿病的療效分析[J]. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(12):1272-1277.
12. Bradley D, Conte C, Mittendorfer B, et al. Gastric bypass and banding equally improve insulin sensitivity and β cell function[J].J Clin Invest, 2012, 122(12):4667-4674.
13. Guidone C, Manco M, Valera-Mora E, et al. Mechanisms ofrecovery from type 2 diabetes after malabsorptive bariatric surgery[J]. Diabetes, 2006, 55(7):2025-2031.
14. Jiménez A, Casamitjana R, Flores L, et al. Long-term effects of sleeve gastrectomy and Roux-en-Y gastric bypass surgery on type 2 diabetes mellitus in morbidly obese subjects[J]. Ann Surg, 2012, 256(6):1023-1029.
15. Jørgensen NB, Jacobsen SH, Dirksen C, et al. Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with type 2 diabetes and normal glucose tolerance[J]. Am J Physiol Endocrinol Metab, 2012, 303(1):122-131.
16. Nadreau E, Baraboi ED, Samson P, et al. Effects of the biliopan-creatic diversion on energy balance in the rat[J]. Int J Obes, 2006,30(3):419-429.
17. Koivisto VA. Insulin therapy in typeⅡ diabetes[J]. Diabetes Care,1993, 16 Suppl 3:29-39.
18. Knudsen LB. Glucagon-like peptide-1:the basis of a new class of treatment for type 2 diabetes[J]. J Med Chem, 2004, 47(17):4128-4134.
19. Chronaiou A, Tsoli M, Kehagias I, et al. Lower ghrelin levels and exaggerated postprandial peptide-YY, glucagon-like peptide-1, and insulin responses, after gastric fundus resection, in patients undergoing Roux-en-Y gastric bypass:a randomized clinical trial[J]. Obes Surg, 2012, 22(11):1761-1770.
20. 鄧治洲, 王烈, 林憶陽, 等. 胃轉(zhuǎn)流術(shù)對非肥胖型2型糖尿病的療效觀察及其對胰高血糖素樣肽-1的影響[J]. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(6):466-469.
21. Wang TT, Hu SY, Gao HD, et al. Ileal transposition controls diabetes as well as modified duodenal jejunal bypass with betterlipid lowering in a nonobese rat model of type Ⅱ diabetes by incre-asing GLP-1[J]. Ann Surg, 2008, 247(6):968-975.
22. Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes[J]. Ann Surg, 2006, 244(5):741-749.
23. Cummings DE, Overduin J. Gastrointestinal regulation of food intake[J]. J Clin Invest, 2007, 117(1):13-23.
24. Kageyama H, F unahashi H, Hirayama M, et al. Morphological analysis of ghrelin and its receptor distribution in the rat pancreas[J]. Regul Pept, 2005, 126(1-2):67-71.
25. Dezaki K, Kakei M, Yada T. Ghrelin uses Galphai2 and activatesvoltage-dependent K+ channels to attenuate glucose-induced Ca2+ signaling and insulin release in islet beta-cells:novel signal transduction of ghrelin[J]. Diabetes, 2007, 56(9):2319-2327.
26. Dimitriadis E, Daskalakis M, Kampa M, et al. Alterations in gut hormones after laparoscopic sleeve gastrectomy:a prospectiveclinical and laboratory investigational study[J]. Ann Surg, 2013,257(4):647-654.
27. 朱占永, 嚴(yán)玲玲, 吳丹, 等. 胃袖狀切除對GK大鼠血糖、ghrelin和胰高血糖素樣肽-1水平的影響[J]. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(6):603-609.
28. Koshy AA, Bobe AM, Brady MJ. Potential mechanisms by which bariatric surgery improves systemic metabolism[J]. Transl Res, 2013, 161(2):63-72.
  1. 1. Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus:a review of current trends[J]. Oman Med J, 2012, 27(4):269-273.
  2. 2. Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus[J]. Ann Surg, 1995, 222(3):339-350.
  3. 3. Salehi M, Prigeon RL, D’Alessio DA. Gastric bypass surgery enhances glucagon-like peptide 1-stimulated postprandial insulin secretion in humans[J]. Diabetes, 2011, 60(9):2308-2314.
  4. 4. Ramos AC, Galvão Neto MP, de Souza YM, et al. Laparoscopic duodenal-jejunal exclusion in the treatment of type 2 diabetes mellitus in patients with BMI<30 kg/m2 (LBMI)[J]. Obes Surg, 2009, 19(3):307-312.
  5. 5. Lemanu DP, Srinivasa S, Singh PP, et al. Laparoscopic sleeve gastrectomy:its place in bariatric surgery for the severely obese patient[J]. N Z Med J, 2012, 125(1359):41-49.
  6. 6. Galli J, Li LS, Glaser A, et al. Genetic analysis of non-insulin dependent diabetes mellitus in the GK rat[J]. Nat Genet, 1996, 12(1):31-37.
  7. 7. Li F, Zhang G, Liang J, et al. Sleeve gastrectomy provides a bettercontrol of diabetes by decreasing ghrelin in the diabetic Goto-Kakizaki rats[J]. J Gastrointest Surg, 2009, 13(12):2302-2308.
  8. 8. de Bona Castelan J, Bettiol J, d’Acampora AJ, et al. Sleeve gastrectomy model in Wistar rats[J]. Obes Surg, 2007, 17(7):957-961.
  9. 9. Pruessner JC, Kirschbaum C, Meinlschmid G, et al. Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change[J]. Psychoneuroendocrinology, 2003, 28(7):916-931.
  10. 10. Pata G, Crea N, Di Betta E, et al. Biliopancreatic diversion with transient gastroplasty and duodenal Switch:long-term results of a multicentric study[J]. Surgery, 2013, 153(3):413-422.
  11. 11. 張曉娟, 杜涓, 杜瀟, 等. 腹腔鏡下胃轉(zhuǎn)流術(shù)治療肥胖型2型糖尿病的療效分析[J]. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(12):1272-1277.
  12. 12. Bradley D, Conte C, Mittendorfer B, et al. Gastric bypass and banding equally improve insulin sensitivity and β cell function[J].J Clin Invest, 2012, 122(12):4667-4674.
  13. 13. Guidone C, Manco M, Valera-Mora E, et al. Mechanisms ofrecovery from type 2 diabetes after malabsorptive bariatric surgery[J]. Diabetes, 2006, 55(7):2025-2031.
  14. 14. Jiménez A, Casamitjana R, Flores L, et al. Long-term effects of sleeve gastrectomy and Roux-en-Y gastric bypass surgery on type 2 diabetes mellitus in morbidly obese subjects[J]. Ann Surg, 2012, 256(6):1023-1029.
  15. 15. Jørgensen NB, Jacobsen SH, Dirksen C, et al. Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with type 2 diabetes and normal glucose tolerance[J]. Am J Physiol Endocrinol Metab, 2012, 303(1):122-131.
  16. 16. Nadreau E, Baraboi ED, Samson P, et al. Effects of the biliopan-creatic diversion on energy balance in the rat[J]. Int J Obes, 2006,30(3):419-429.
  17. 17. Koivisto VA. Insulin therapy in typeⅡ diabetes[J]. Diabetes Care,1993, 16 Suppl 3:29-39.
  18. 18. Knudsen LB. Glucagon-like peptide-1:the basis of a new class of treatment for type 2 diabetes[J]. J Med Chem, 2004, 47(17):4128-4134.
  19. 19. Chronaiou A, Tsoli M, Kehagias I, et al. Lower ghrelin levels and exaggerated postprandial peptide-YY, glucagon-like peptide-1, and insulin responses, after gastric fundus resection, in patients undergoing Roux-en-Y gastric bypass:a randomized clinical trial[J]. Obes Surg, 2012, 22(11):1761-1770.
  20. 20. 鄧治洲, 王烈, 林憶陽, 等. 胃轉(zhuǎn)流術(shù)對非肥胖型2型糖尿病的療效觀察及其對胰高血糖素樣肽-1的影響[J]. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(6):466-469.
  21. 21. Wang TT, Hu SY, Gao HD, et al. Ileal transposition controls diabetes as well as modified duodenal jejunal bypass with betterlipid lowering in a nonobese rat model of type Ⅱ diabetes by incre-asing GLP-1[J]. Ann Surg, 2008, 247(6):968-975.
  22. 22. Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes[J]. Ann Surg, 2006, 244(5):741-749.
  23. 23. Cummings DE, Overduin J. Gastrointestinal regulation of food intake[J]. J Clin Invest, 2007, 117(1):13-23.
  24. 24. Kageyama H, F unahashi H, Hirayama M, et al. Morphological analysis of ghrelin and its receptor distribution in the rat pancreas[J]. Regul Pept, 2005, 126(1-2):67-71.
  25. 25. Dezaki K, Kakei M, Yada T. Ghrelin uses Galphai2 and activatesvoltage-dependent K+ channels to attenuate glucose-induced Ca2+ signaling and insulin release in islet beta-cells:novel signal transduction of ghrelin[J]. Diabetes, 2007, 56(9):2319-2327.
  26. 26. Dimitriadis E, Daskalakis M, Kampa M, et al. Alterations in gut hormones after laparoscopic sleeve gastrectomy:a prospectiveclinical and laboratory investigational study[J]. Ann Surg, 2013,257(4):647-654.
  27. 27. 朱占永, 嚴(yán)玲玲, 吳丹, 等. 胃袖狀切除對GK大鼠血糖、ghrelin和胰高血糖素樣肽-1水平的影響[J]. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(6):603-609.
  28. 28. Koshy AA, Bobe AM, Brady MJ. Potential mechanisms by which bariatric surgery improves systemic metabolism[J]. Transl Res, 2013, 161(2):63-72.