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Published in: Surgical Endoscopy 7/2013

01-07-2013

Changes in GIP gene expression following bariatric surgery

Authors: Erin Moran-Atkin, Fred Brody, Sidney W. Fu, Marcos Rojkind

Published in: Surgical Endoscopy | Issue 7/2013

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Abstract

Background

After bariatric surgery, there is a significant improvement in type 2 diabetes (T2D). T2D has been linked to incretins, including glucose-dependent insulinotropic polypeptide (GIP). Analysis of bariatric surgery patients may help to understand the link between GIP and T2D.

Methods

Twenty-three morbidly obese patients underwent Roux-en-Y gastric bypass (RYGB) or gastric banding. Overall, there were 12 RYGB (5 T2D; 7 nondiabetic) patients and 11 gastric band (7 T2D; 4 nondiabetic) patients. Preoperative and postoperative blood samples were collected. Total RNA was extracted, cDNA synthesized, and real-time quantitative PCR were used to quantify gene expression. Student’s t test was used for statistical analysis.

Results

Postoperatively, T2D resolved or improved in 83.3 % (10/12) of the diabetic patients. Six (4 RYGB, 2 bands) patients discontinued hypoglycemic medications and four (3 RYGB, 1 band) patients discontinued the majority of their hypoglycemic agents. The remaining two diabetic patients (bands) showed no improvement. Postoperative GIP gene expression increased 4.36-fold (p = 0.02) in diabetic RYGB patients, whereas diabetic band patients increased 1.4-fold (p = 0.25). All diabetic patients with either resolution or improvement of T2D, had a 3.4-fold increase (p = 0.01) but nonresponders decreased 0.69-fold (p = 0.41). Nondiabetic RYGB patients increased 2.21-fold (p = 0.07) versus a 0.81-fold (p = 0.37) decrease of nondiabetic band patients.

Conclusions

This is one of the initial studies that show a significant increase in GIP gene expression following a RYGB. This increase correlates with the clinical resolution of T2D. The anatomical changes after RYGB may account for these changes. Based on this data, GIP may be a key peptide in the “foregut hypothesis” for resolution of T2D.
Literature
1.
4.
go back to reference Cowie CC, Rust KF, Byrd-Holt DD, Eberhardt MS, Flegal KM, Engelgau MM, Saydah SH, Williams DE, Geiss LS, Gregg EW (2006) Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health And Nutrition Examination Survey 1999–2002. Diabetes Care 29:1263–1268. doi:10.2337/dc06-0062 PubMedCrossRef Cowie CC, Rust KF, Byrd-Holt DD, Eberhardt MS, Flegal KM, Engelgau MM, Saydah SH, Williams DE, Geiss LS, Gregg EW (2006) Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health And Nutrition Examination Survey 1999–2002. Diabetes Care 29:1263–1268. doi:10.​2337/​dc06-0062 PubMedCrossRef
5.
go back to reference Hickey MS, Pories WJ, MacDonald KG Jr, Cory KA, Dohm GL, Swanson, Israel RG, Barakat HA, Considine RV, Caro JF, Houmard JA (1998) A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut? Ann Surg 227:637–644; discussion 643–644PubMedCrossRef Hickey MS, Pories WJ, MacDonald KG Jr, Cory KA, Dohm GL, Swanson, Israel RG, Barakat HA, Considine RV, Caro JF, Houmard JA (1998) A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut? Ann Surg 227:637–644; discussion 643–644PubMedCrossRef
6.
go back to reference Rubino F, Forgione A, Cummings DE, Vix M, Gnuli D, Mingrone G, Castagneto M, Marescaux J (2006) The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg 244:741–749. doi:10.1097/01.sla.0000224726.61448.1b PubMedCrossRef Rubino F, Forgione A, Cummings DE, Vix M, Gnuli D, Mingrone G, Castagneto M, Marescaux J (2006) The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg 244:741–749. doi:10.​1097/​01.​sla.​0000224726.​61448.​1b PubMedCrossRef
8.
go back to reference Nauck MA, Homberger E, Siegel EG, Allen RC, Eaton RP, Ebert R, Creutzfeldt W (1986) Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 63:492–498PubMedCrossRef Nauck MA, Homberger E, Siegel EG, Allen RC, Eaton RP, Ebert R, Creutzfeldt W (1986) Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 63:492–498PubMedCrossRef
9.
go back to reference Saxena R, Hivert MF, Langenberg C, Tanaka T, Pankow JS, Vollenweider P, Lyssenko V, Bouatia-Naji N, Dupuis J, Jackson AU, Kao WH, Li M, Glazer NL, Manning AK, Luan J, Stringham HM, Prokopenko I, Johnson T, Grarup N, Boesgaard TW, Lecoeur C, Shrader P, O’Connell J, Ingelsson E, Couper DJ, Rice K, Song K, Andreasen CH, Dina C, Kottgen A, Le Bacquer O, Pattou F, Taneera J, Steinthorsdottir V, Rybin D, Ardlie K, Sampson M, Qi L, van Hoek M, Weedon MN, Aulchenko YS, Voight BF, Grallert H, Balkau B, Bergman RN, Bielinski SJ, Bonnefond A, Bonnycastle LL, Borch-Johnsen K, Bottcher Y, Brunner E, Buchanan TA, Bumpstead SJ, Cavalcanti-Proenca C, Charpentier G, Chen YD, Chines PS, Collins FS, Cornelis M, J Crawford G, Delplanque J, Doney A, Egan JM, Erdos MR, Firmann M, Forouhi NG, Fox CS, Goodarzi MO, Graessler J, Hingorani A, Isomaa B, Jorgensen T, Kivimaki M, Kovacs P, Krohn K, Kumari M, Lauritzen T, Levy-Marchal C, Mayor V, McAteer JB, Meyre D, Mitchell BD, Mohlke KL, Morken MA, Narisu N, Palmer CN, Pakyz R, Pascoe L, Payne F, Pearson D, Rathmann W, Sandbaek A, Sayer AA, Scott LJ, Sharp SJ, Sijbrands E, Singleton A, Siscovick DS, Smith NL, Sparso T, Swift AJ, Syddall H, Thorleifsson G, Tonjes A, Tuomi T, Tuomilehto J, Valle TT, Waeber G, Walley A, Waterworth DM, Zeggini E, Zhao JH, GIANT consortium, MAGIC investigators, Illig T, Wichmann HE, Wilson JF, van Duijn C, Hu FB, Morris AD, Frayling TM, Hattersley AT, Thorsteinsdottir U, Stefansson K, Nilsson P, Syvanen AC, Shuldiner AR, Walker M, Bornstein SR, Schwarz P, Williams GH, Nathan DM, Kuusisto J, Laakso M, Cooper C, Marmot M, Ferrucci L, Mooser V, Stumvoll M, Loos RJ, Altshuler D, Psaty BM, Rotter JI, Boerwinkle E, Hansen T, Pedersen O, Florez JC, McCarthy MI, Boehnke M, Barroso I, Sladek R, Froguel P, Meigs JB, Groop L, Wareham NJ, Watanabe RM (2010) Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet 42:142–148, doi:10.1038/ng.521 Saxena R, Hivert MF, Langenberg C, Tanaka T, Pankow JS, Vollenweider P, Lyssenko V, Bouatia-Naji N, Dupuis J, Jackson AU, Kao WH, Li M, Glazer NL, Manning AK, Luan J, Stringham HM, Prokopenko I, Johnson T, Grarup N, Boesgaard TW, Lecoeur C, Shrader P, O’Connell J, Ingelsson E, Couper DJ, Rice K, Song K, Andreasen CH, Dina C, Kottgen A, Le Bacquer O, Pattou F, Taneera J, Steinthorsdottir V, Rybin D, Ardlie K, Sampson M, Qi L, van Hoek M, Weedon MN, Aulchenko YS, Voight BF, Grallert H, Balkau B, Bergman RN, Bielinski SJ, Bonnefond A, Bonnycastle LL, Borch-Johnsen K, Bottcher Y, Brunner E, Buchanan TA, Bumpstead SJ, Cavalcanti-Proenca C, Charpentier G, Chen YD, Chines PS, Collins FS, Cornelis M, J Crawford G, Delplanque J, Doney A, Egan JM, Erdos MR, Firmann M, Forouhi NG, Fox CS, Goodarzi MO, Graessler J, Hingorani A, Isomaa B, Jorgensen T, Kivimaki M, Kovacs P, Krohn K, Kumari M, Lauritzen T, Levy-Marchal C, Mayor V, McAteer JB, Meyre D, Mitchell BD, Mohlke KL, Morken MA, Narisu N, Palmer CN, Pakyz R, Pascoe L, Payne F, Pearson D, Rathmann W, Sandbaek A, Sayer AA, Scott LJ, Sharp SJ, Sijbrands E, Singleton A, Siscovick DS, Smith NL, Sparso T, Swift AJ, Syddall H, Thorleifsson G, Tonjes A, Tuomi T, Tuomilehto J, Valle TT, Waeber G, Walley A, Waterworth DM, Zeggini E, Zhao JH, GIANT consortium, MAGIC investigators, Illig T, Wichmann HE, Wilson JF, van Duijn C, Hu FB, Morris AD, Frayling TM, Hattersley AT, Thorsteinsdottir U, Stefansson K, Nilsson P, Syvanen AC, Shuldiner AR, Walker M, Bornstein SR, Schwarz P, Williams GH, Nathan DM, Kuusisto J, Laakso M, Cooper C, Marmot M, Ferrucci L, Mooser V, Stumvoll M, Loos RJ, Altshuler D, Psaty BM, Rotter JI, Boerwinkle E, Hansen T, Pedersen O, Florez JC, McCarthy MI, Boehnke M, Barroso I, Sladek R, Froguel P, Meigs JB, Groop L, Wareham NJ, Watanabe RM (2010) Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet 42:142–148, doi:10.​1038/​ng.​521
12.
go back to reference Pories WJ, MacDonald KG Jr, Morgan EJ, Sinha MK, Dohm GL, Swanson MS, Barakat HA, Khazanie PG, Leggett-Frazier N, Long SD (1992) Surgical treatment of obesity and its effect on diabetes: 10-year follow-up. Am J Clin Nutr 55:582S–585SPubMed Pories WJ, MacDonald KG Jr, Morgan EJ, Sinha MK, Dohm GL, Swanson MS, Barakat HA, Khazanie PG, Leggett-Frazier N, Long SD (1992) Surgical treatment of obesity and its effect on diabetes: 10-year follow-up. Am J Clin Nutr 55:582S–585SPubMed
15.
go back to reference Trumper A, Trumper K, Trusheim H, Arnold R, Goke B, Horsch D (2001) Glucose-dependent insulinotropic polypeptide is a growth factor for beta (INS-1) cells by pleiotropic signaling. Mol Endocrinol 15:1559–1570PubMedCrossRef Trumper A, Trumper K, Trusheim H, Arnold R, Goke B, Horsch D (2001) Glucose-dependent insulinotropic polypeptide is a growth factor for beta (INS-1) cells by pleiotropic signaling. Mol Endocrinol 15:1559–1570PubMedCrossRef
16.
17.
go back to reference Rubino F, Gagner M, Gentileschi P, Kini S, Fukuyama S, Feng J, Diamond E (2004) The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg 240:236–242PubMedCrossRef Rubino F, Gagner M, Gentileschi P, Kini S, Fukuyama S, Feng J, Diamond E (2004) The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg 240:236–242PubMedCrossRef
18.
go back to reference Clements RH, Gonzalez QH, Long CI, Wittert G, Laws HL (2004) Hormonal changes after Roux-en Y gastric bypass for morbid obesity and the control of type-II diabetes mellitus. Am Surg 70:1–4; discussion 4–5PubMed Clements RH, Gonzalez QH, Long CI, Wittert G, Laws HL (2004) Hormonal changes after Roux-en Y gastric bypass for morbid obesity and the control of type-II diabetes mellitus. Am Surg 70:1–4; discussion 4–5PubMed
19.
go back to reference Laferrere B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, Kovack B, Bawa B, Koshy N, Lee H, Yapp K, Olivan B (2008) Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab 93:2479–2485. doi:10.1210/jc.2007-2851 PubMedCrossRef Laferrere B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, Kovack B, Bawa B, Koshy N, Lee H, Yapp K, Olivan B (2008) Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab 93:2479–2485. doi:10.​1210/​jc.​2007-2851 PubMedCrossRef
Metadata
Title
Changes in GIP gene expression following bariatric surgery
Authors
Erin Moran-Atkin
Fred Brody
Sidney W. Fu
Marcos Rojkind
Publication date
01-07-2013
Publisher
Springer-Verlag
Published in
Surgical Endoscopy / Issue 7/2013
Print ISSN: 0930-2794
Electronic ISSN: 1432-2218
DOI
https://doi.org/10.1007/s00464-012-2764-8

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