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Glucose-dependent insulinotropic polypeptide - a new link in the development of obesity

https://doi.org/10.14341/omet2015116-19

Abstract

Objective. Glucose-dependent insulinotropic polypeptide (GIP) as well as glucagon-like peptide-1 (GLP-1) is intestinal incretin hormone that stimulates insulin secretion in response to feeding. Much evidence of GIP contribution to obesity development has been found recently.

Aim. The aim of the study was to evaluate glucose-stimulated GIP and GLP-1 secretion in people with type 2 diabetes (T2D) risk factors and different body mass index (BMI).

Materials and methods. Total GIP and GLP-1 secretion was estimated in 127 patients with T2D risk factors during OGTT (75 g glucose) on 0, 30 and 120 minutes.

Results. Patients with BMI≥ 35 kg/m2 had significantly higher fasting and stimulated GIP levels than participants with less BMI. GIP secretion was also higher in patients was insulinresistance, estimated by HOMA-IR, comparing to non-insulinresistant patients. Difference in GLP-1 secretion in patients within several BMI groups was nonsignificant.

Conclusion. Our results suggest GIP is related to obesity degree, that means it can play a role in lipid metabolism and obesity development. 

About the Authors

Ekaterina Alekseevna Shestakova
Endocrinology Research Centre
Russian Federation
PhD, researcher at the Interventional Cardiology Department


Aleksandr Victorovich Il'in
Endocrinology Research Centre
Russian Federation
Head of the Laboratory


Marina Vladimirovna Shestakova
Endocrinology Research Centre
Russian Federation
MD, PhD. professor., corresponding member of  Russian Academy of Sciences, Director of Institute of Diabetes  Head of the Endocrinology and Diabetology Department at Pediatric Faculty of The First Sechenov Moscow State Medical University


Ivan Ivanovich Dedov
Endocrinology Research Centre
Russian Federation
MD, Ph.D, academician of the Russian Academy of Sciences, Director


References

1. Baggio LL, Drucker DJ. Biology of Incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131-57. PMID:17498508 doi: 10.1053/j.gastro.2007.03.054.

2. Holst JJ. On the Physiology of GIP and GLP-1. Hormone and Metabolic Research. 2004;36(11/12):747-54. PMID:15655703 doi: 10.1055/s-2004-826158.

3. Meier JJ, Nauck MA. Glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide. Best Practice & Research Clinical Endocrinology & Metabolism. 2004;18(4):587-606. PMID:15533777 doi: 10.1016/j.beem.2004.08.007.

4. Дедов И.И., Шестакова М.В. Инкретины: новая веха в лечении сахарного диабета 2 типа. - М.: Дипак; 2010. 92 с. [Dedov II, Shestakova MV. Inkretiny: novaya vekha v lechenii sakharnogo diabeta 2 tipa. Moscow: Dipak; 2010. (In Russ).]

5. Green BD, Flatt PR. Incretin hormone mimetics and analogues in diabetes therapeutics. Best Practice & Research Clinical Endocrinology & Metabolism. 2007;21(4):497-516. PMID:18054732 doi: 10.1016/j.beem.2007.09.003.

6. Yip RGC, Boylan MO, Kieffer TJ, Wolfe MM. Functional GIP Receptors Are Present on Adipocytes. Endocrinology. 1998;139(9):4004-7. PMID:9724057 doi: 10.1210/endo.139.9.6288.

7. Carr RD, Larsen MO, Jelic K, Lindgren O, Vikman J, Holst JJ, et al. Secretion and Dipeptidyl Peptidase-4-Mediated Metabolism of Incretin Hormones after a Mixed Meal or Glucose Ingestion in Obese Compared to Lean, Nondiabetic Men. The Journal of Clinical Endocrinology & Metabolism. 2010;95(2):872-8. PMID:20008019 doi: 10.1210/jc.2009-2054.

8. Muscelli E, Mari A, Casolaro A, Camastra S, Seghieri G, Gastaldelli A, et al. Separate Impact of Obesity and Glucose Tolerance on the Incretin Effect in Normal Subjects and Type 2 Diabetic Patients. Diabetes. 2007;57(5):1340-8. PMID:18162504 doi: 10.2337/db07-1315.

9. Toft-Nielsen M-B, Damholt MB, Madsbad S, Hilsted LM, Hughes TE, Michelsen BK, et al. Determinants of the Impaired Secretion of Glucagon-Like Peptide-1 in Type 2 Diabetic Patients. The Journal of Clinical Endocrinology & Metabolism. 2001;86(8):3717-23. PMID:11502801 doi: 10.1210/jcem.86.8.7750.

10. Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nature Medicine. 2002;8(7):738-42. PMID:12068290 doi: 10.1038/nm727.

11. Gault VA, Irwin N, Green BD, McCluskey JT, Greer B, Bailey CJ, et al. Chemical Ablation of Gastric Inhibitory Polypeptide Receptor Action by Daily (Pro3)GIP Administration Improves Glucose Tolerance and Ameliorates Insulin Resistance and Abnormalities of Islet Structure in Obesity-Related Diabetes. Diabetes. 2005;54(8):2436-46. PMID:16046312 doi: 10.2337/diabetes.54.8.2436.

12. Gault VA, McClean PL, Cassidy RS, Irwin N, Flatt PR. Chemical gastric inhibitory polypeptide receptor antagonism protects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat and cafeteria diets. Diabetologia. 2007;50(8):1752-62. PMID:17558485 doi: 10.1007/s00125-007-0710-4.

13. Irwin N, McClean PL, O’Harte FPM, Gault VA, Harriott P, Flatt PR. Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist (Pro3)GIP prevents the development of diabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice. Diabetologia. 2007;50(7):1532-40. PMID:17486314 doi: 10.1007/s00125-007-0692-2.

14. McClean PL, Irwin N, Cassidy RS, Holst JJ, Gault VA, Flatt PR. GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet. AJP: Endocrinology and Metabolism. 2007;293(6):E1746-E55. PMID:17848629 doi: 10.1152/ajpendo.00460.2007.

15. Bartolomucci A, Fulurija A, Lutz TA, Sladko K, Osto M, Wielinga PY, et al. Vaccination against GIP for the Treatment of Obesity. PLoS ONE. 2008;3(9):e3163. PMID:18779862 doi: 10.1371/journal.pone.0003163.

16. Holst JJ, Knop FK, Vilsboll T, Krarup T, Madsbad S. Loss of Incretin Effect Is a Specific, Important, and Early Characteristic of Type 2 Diabetes. Diabetes Care. 2011;34(Supplement_2):S251-S7. PMID:21525464 doi: 10.2337/dc11-s227.

17. Knop FK, Aaboe K, Vilsbøll T, Vølund A, Holst JJ, Krarup T, et al. Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity. Diabetes, Obesity and Metabolism. 2012;14(6):500-10. PMID:22171657 doi: 10.1111/j.1463-1326.2011.01549.x.

18. Vilsbøll T, Krarup T, Sonne J, Madsbad S, Vølund A, Juul AG, et al. Incretin Secretion in Relation to Meal Size and Body Weight in Healthy Subjects and People with Type 1 and Type 2 Diabetes Mellitus. The Journal of Clinical Endocrinology & Metabolism. 2003;88(6):2706-13. PMID:12788877 doi: 10.1210/jc.2002-021873.


Review

For citations:


Shestakova E.A., Il'in A.V., Shestakova M.V., Dedov I.I. Glucose-dependent insulinotropic polypeptide - a new link in the development of obesity. Obesity and metabolism. 2015;12(1):16-19. (In Russ.) https://doi.org/10.14341/omet2015116-19

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