Effects of gastric bypass on FoxO1 expression in the liver and pancreas of diabetic rats

Abstract Aim: To explore the mechanism by which gastric bypass surgery (GBS) ameliorates type 2 diabetes mellitus (T2DM) by investigating whether FoxO1 (a transcription factor that plays a crucial role in the regulation of glycolipid metabolism) expression is altered in the liver and pancreatic islet cells in a rat model of GBS-treated T2DM. Methods: Sprague-Dawley rats were randomly divided into four groups (n = 10 rats each): diabetic rats treated by GBS (DM + GBS), diabetic rats subjected to sham operation (DM + sham), normal control rats (control), and diabetic rats without surgery (DM). Fasting levels of blood glucose (BG), insulin, and glucagon-like peptide-1 (GLP-1) were measured in all groups before and 4, 8, 16, and 24 weeks after operation. Rats were killed 24 weeks after surgery. Liver and pancreas expressions of FoxO1 were investigated by immunohistochemistry and Western blotting analyses. Results: In the DM + GBS group, fasting BG before and 24 weeks after surgery decreased from 20.2 ± 2.1 to 7.7 ± 1.1 mmol/L, respectively; fasting insulin showed no change (2.9 ± 0.1 and 3.0 ± 0.1 mU/L, respectively); and fasting GLP-1 increased from 8.7 ± 0.9 to 23.5 ± 0.2 pmol/L, respectively. Fasting BG levels after surgery in the DM + GBS group were significantly lower than those in the DM + sham and DM groups. FoxO1 expression levels in the liver and pancreatic islets of the DM + GBS group were reduced compared to those in the DM + sham and DM groups. FoxO1 in the pancreatic β-cells was expressed mainly in the cytoplasm. Conclusions: Gastric bypass may improve type 2 diabetes mellitus by changing FoxO1 expression in the liver and pancreatic islet cells.

[1]  S. El-Hasani,et al.  Durability of Roux-en-Y gastric bypass surgery: a meta-regression study. , 2015, Annals of surgery.

[2]  T. Kitamura,et al.  FoxO1 Gain of Function in the Pancreas Causes Glucose Intolerance, Polycystic Pancreas, and Islet Hypervascularization , 2012, PloS one.

[3]  T. Kitamura,et al.  Overexpression of FoxO1 in the hypothalamus and pancreas causes obesity and glucose intolerance. , 2012, Endocrinology.

[4]  N. Abumrad,et al.  Hepatic and Peripheral Insulin Sensitivity and Diabetes Remission at 1 Month After Roux-en-Y Gastric Bypass Surgery in Patients Randomized to Omentectomy , 2011, Diabetes Care.

[5]  W. Gu,et al.  Glucagon-Like Peptide 1 Inhibits the Sirtuin Deacetylase SirT1 to Stimulate Pancreatic β-Cell Mass Expansion , 2011, Diabetes.

[6]  M. Nakazato,et al.  Glucagon-like peptide-1 and candesartan additively improve glucolipotoxicity in pancreatic β-cells. , 2011, Metabolism: clinical and experimental.

[7]  A. Morabito,et al.  Long-term Prevention of Mortality in Morbid Obesity Through Bariatric Surgery. A Systematic Review and Meta-analysis of Trials Performed With Gastric Banding and Gastric Bypass , 2011, Annals of surgery.

[8]  K. Kaestner,et al.  FoxOs Function Synergistically to Promote Glucose Production* , 2010, The Journal of Biological Chemistry.

[9]  Yu Bai,et al.  Roux-en-Y gastric bypass promotes expression of PDX-1 and regeneration of beta-cells in Goto-Kakizaki rats. , 2010, World journal of gastroenterology.

[10]  K. Dou,et al.  Prevalence of diabetes among men and women in China. , 2010, The New England journal of medicine.

[11]  P. Roach,et al.  Molecular Characterization of Insulin-Mediated Suppression of Hepatic Glucose Production In Vivo , 2010, Diabetes.

[12]  M. Jensen,et al.  Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. , 2009, The American journal of medicine.

[13]  J. Teixeira,et al.  Do Incretins Play a Role in the Remission of Type 2 Diabetes after Gastric Bypass Surgery: What are the Evidence? , 2009, Obesity surgery.

[14]  Jing Li,et al.  The Characterization of High-Fat Diet and Multiple Low-Dose Streptozotocin Induced Type 2 Diabetes Rat Model , 2009, Experimental diabetes research.

[15]  F. Horber,et al.  Severe Recurrent Hypoglycemia after Gastric Bypass Surgery , 2008, Obesity surgery.

[16]  L. N. Valenti,et al.  Increased Expression and Activity of the Transcription Factor FOXO1 in Nonalcoholic Steatohepatitis , 2007, Diabetes.

[17]  T. Kitamura,et al.  Role of FoxO Proteins in Pancreatic β Cells , 2007 .

[18]  S. Ikramuddin,et al.  Hyperinsulinemic Hypoglycemia Developing Late after Gastric Bypass , 2007, Obesity surgery.

[19]  D. Accili,et al.  Transcription Factor FoxO1 Mediates Glucagon-Like Peptide-1 Effects on Pancreatic β-Cell Mass , 2006, Diabetes.

[20]  K. Heidenreich,et al.  FoxO1 Regulates Multiple Metabolic Pathways in the Liver , 2006, Journal of Biological Chemistry.

[21]  R. Batterham,et al.  Gut Hormone Profiles Following Bariatric Surgery Favor an Anorectic State, Facilitate Weight Loss, and Improve Metabolic Parameters , 2006, Annals of surgery.

[22]  S. Woods,et al.  Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats. , 2005, American journal of physiology. Endocrinology and metabolism.

[23]  Henry Buchwald,et al.  Bariatric surgery: a systematic review and meta-analysis. , 2004, JAMA.

[24]  A. Patriti,et al.  Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. , 2004, Annals of surgery.

[25]  D. Cummings,et al.  Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. , 2004, The Journal of clinical endocrinology and metabolism.

[26]  L. Kuller,et al.  Effect of Laparoscopic Roux-En Y Gastric Bypass on Type 2 Diabetes Mellitus , 2003 .

[27]  J. Holst,et al.  Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes. , 2003, The Journal of clinical endocrinology and metabolism.

[28]  Y. Kido,et al.  The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. , 2002, The Journal of clinical investigation.

[29]  D. Accili,et al.  The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. , 2001, The Journal of clinical investigation.

[30]  B. Charbonnel,et al.  Managing type 2 diabetes in France: the ECODIA survey. , 2000, Diabetes & metabolism.

[31]  M. Greenberg,et al.  Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor , 1999, Cell.

[32]  W. Pories,et al.  The Effectiveness of Gastric Bypass Over Gastric Partition in Morbid Obesity: Consequence of Distal Gastric and Duodenal Exclusion , 1982, Annals of surgery.

[33]  T Szkudelski,et al.  The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. , 2001, Physiological research.