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Published in: Obesity Surgery 9/2011

01-09-2011 | Animal Research

Roux-en-Y Gastric Bypass-Induced Improvement of Glucose Tolerance and Insulin Resistance in Type 2 Diabetic Rats Are Mediated by Glucagon-Like Peptide-1

Authors: Yuan Liu, Yong Zhou, Yong Wang, Donghua Geng, Jingang Liu

Published in: Obesity Surgery | Issue 9/2011

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Abstract

Background

The aim of this study was to investigate the effects of Roux-en-Y gastric bypass (RYGB) on glucose tolerance and insulin resistance in type 2 diabetic rats and the possible mechanisms involved in this process.

Methods

Thirty Goto-Kakizaki (GK) rats were randomly divided into three groups: RYGB operation, sham operation, and food restriction groups. Ten Wistar rats were used as non-diabetic control. The body weight and food consumption of rats were recorded 1 week before or every week after surgery. The fasting blood sugar and oral glucose tolerance test were performed using blood glucose meter. The levels of plasma insulin or glucagon-like peptide-1 (GLP-1) were evaluated by enzyme-linked immunosorbent assay. The insulin resistance was quantified using homeostasis model assessment method. The expression of GLP-1 receptor, Bcl-2, Bax, and caspase-3 was determined by Western blotting.

Results

Our results revealed that RYGB efficiently improved both glucose tolerance and insulin resistance in GK diabetic rats by upregulating GLP-1/GLP-1R expression. In addition, GLP-1R agonist exendin-4 dose-dependently increased insulin secretion in RIN-m5F cells and regulated the proliferation and apoptosis of these cells.

Conclusions

RYGB provides a valuable therapeutic option for patients with type 2 diabetes. GLP-1 may contribute to the regulation of pancreatic β-cell function through its receptor following RYGB.
Literature
1.
go back to reference Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005;365(9467):1333–46.PubMedCrossRef Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005;365(9467):1333–46.PubMedCrossRef
2.
go back to reference DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131(4):281–303.PubMed DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131(4):281–303.PubMed
3.
go back to reference Schauer PR et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003;238(4):467–84. discussion 84–5.PubMed Schauer PR et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003;238(4):467–84. discussion 84–5.PubMed
4.
go back to reference Pories WJ et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222(3):339–50. discussion 350–2.PubMedCrossRef Pories WJ et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222(3):339–50. discussion 350–2.PubMedCrossRef
5.
go back to reference Rubino F et al. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg. 2004;240(2):236–42.PubMedCrossRef Rubino F et al. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg. 2004;240(2):236–42.PubMedCrossRef
6.
go back to reference Cummings DE, Overduin J, Foster-Schubert KE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab. 2004;89(6):2608–15.PubMedCrossRef Cummings DE, Overduin J, Foster-Schubert KE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab. 2004;89(6):2608–15.PubMedCrossRef
7.
go back to reference Mojsov S et al. Preproglucagon gene expression in pancreas and intestine diversifies at the level of post-translational processing. J Biol Chem. 1986;261(25):11880–9.PubMed Mojsov S et al. Preproglucagon gene expression in pancreas and intestine diversifies at the level of post-translational processing. J Biol Chem. 1986;261(25):11880–9.PubMed
9.
go back to reference Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368(9548):1696–705.PubMedCrossRef Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368(9548):1696–705.PubMedCrossRef
10.
go back to reference Gerdes J et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984;133(4):1710–5.PubMed Gerdes J et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984;133(4):1710–5.PubMed
11.
go back to reference Marzo I et al. The permeability transition pore complex: a target for apoptosis regulation by caspases and bcl-2-related proteins. J Exp Med. 1998;187(8):1261–71.PubMedCrossRef Marzo I et al. The permeability transition pore complex: a target for apoptosis regulation by caspases and bcl-2-related proteins. J Exp Med. 1998;187(8):1261–71.PubMedCrossRef
12.
go back to reference Kindel TL et al. Duodenal–jejunal exclusion improves glucose tolerance in the diabetic, Goto-Kakizaki rat by a GLP-1 receptor-mediated mechanism. J Gastrointest Surg. 2009;13(10):1762–72.PubMedCrossRef Kindel TL et al. Duodenal–jejunal exclusion improves glucose tolerance in the diabetic, Goto-Kakizaki rat by a GLP-1 receptor-mediated mechanism. J Gastrointest Surg. 2009;13(10):1762–72.PubMedCrossRef
13.
go back to reference Korner J et al. Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. J Clin Endocrinol Metab. 2005;90(1):359–65.PubMedCrossRef Korner J et al. Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. J Clin Endocrinol Metab. 2005;90(1):359–65.PubMedCrossRef
14.
go back to reference Korner J et al. Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels. Obesity (Silver Spring). 2006;14(9):1553–61.CrossRef Korner J et al. Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels. Obesity (Silver Spring). 2006;14(9):1553–61.CrossRef
15.
go back to reference Patriti A et al. The enteroinsular axis and the recovery from type 2 diabetes after bariatric surgery. Obes Surg. 2004;14(6):840–8.PubMedCrossRef Patriti A et al. The enteroinsular axis and the recovery from type 2 diabetes after bariatric surgery. Obes Surg. 2004;14(6):840–8.PubMedCrossRef
16.
17.
go back to reference Pories WJ, Albrecht RJ. Etiology of type II diabetes mellitus: role of the foregut. World J Surg. 2001;25(4):527–31.PubMedCrossRef Pories WJ, Albrecht RJ. Etiology of type II diabetes mellitus: role of the foregut. World J Surg. 2001;25(4):527–31.PubMedCrossRef
18.
go back to reference Rubino F, Gagner M. Potential of surgery for curing type 2 diabetes mellitus. Ann Surg. 2002;236(5):554–9.PubMedCrossRef Rubino F, Gagner M. Potential of surgery for curing type 2 diabetes mellitus. Ann Surg. 2002;236(5):554–9.PubMedCrossRef
19.
go back to reference Patriti A et al. Early improvement of glucose tolerance after ileal transposition in a non-obese type 2 diabetes rat model. Obes Surg. 2005;15(9):1258–64.PubMedCrossRef Patriti A et al. Early improvement of glucose tolerance after ileal transposition in a non-obese type 2 diabetes rat model. Obes Surg. 2005;15(9):1258–64.PubMedCrossRef
20.
go back to reference Deacon CF et al. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes. 1995;44(9):1126–31.PubMedCrossRef Deacon CF et al. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes. 1995;44(9):1126–31.PubMedCrossRef
Metadata
Title
Roux-en-Y Gastric Bypass-Induced Improvement of Glucose Tolerance and Insulin Resistance in Type 2 Diabetic Rats Are Mediated by Glucagon-Like Peptide-1
Authors
Yuan Liu
Yong Zhou
Yong Wang
Donghua Geng
Jingang Liu
Publication date
01-09-2011
Publisher
Springer-Verlag
Published in
Obesity Surgery / Issue 9/2011
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI
https://doi.org/10.1007/s11695-011-0388-z

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