Abstract
Our experiment investigated the mRNA expression of intestinal gonadotropin-releasing hormone (GnRH), proglucagon (PG), and glucagon-like peptide 1 receptor (GLP-1R) in the jejunum, ileum, and colon of rats fed with high-fat diet and Goto-Kakizaki (GK) rats and revealed the physiological role of intestinal GnRH. We found that the GnRH and PG mRNA levels in high-cholesterol (HCh) diet were higher than in the control. However, the GnRH receptor (GnRHR) and GLP-1R mRNA levels did not differ significantly between HCh and control. The GnRH, PG, and GLP-1R mRNA levels in GK rats were lower, respectively, than those in control rats, while the GnRHR levels did not differ significantly between GK rats and control rats. There were no difference in GnRH, PG, GnRHR, and GLP-1R mRNA levels in the ileum and colon tissue between HCh and control rats. The GnRH mRNA levels of GK rats were lower than those in control rats; however, the PG, GLP-1R, and GnRHR levels did not differ significantly between GK and control rats. The GLP-1R mRNA levels of GK rats were lower than those in control rats. The GnRH mRNA expression showed positive correlation with PG mRNA expression in different intestinal sections. The GnRH level in the jejunum showed a significant effect on blood glucose level, while the PG level in the jejunum showed a significant effect on insulin level. This may imply that, compared with the ileum and colon, the jejunum had greater impact on glucose metabolism; furthermore, GnRH might interact with intestinal GLP-1 and GLP-2 through the paracrine and autocrine ways and then regulate glucose metabolism and insulin secretion.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12022-009-9086-y/MediaObjects/12022_2009_9086_Fig1_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12022-009-9086-y/MediaObjects/12022_2009_9086_Fig2_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12022-009-9086-y/MediaObjects/12022_2009_9086_Fig3_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12022-009-9086-y/MediaObjects/12022_2009_9086_Fig4_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12022-009-9086-y/MediaObjects/12022_2009_9086_Fig5_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12022-009-9086-y/MediaObjects/12022_2009_9086_Fig6_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12022-009-9086-y/MediaObjects/12022_2009_9086_Fig7_HTML.gif)
Similar content being viewed by others
References
Moore B, Eille ES, Abram JH. On the treatment of diabetes mellitus by acid extract of duodenal mucous membrane. Biochem J 1:28–38, 1906.
Nauck MA, Homberger E, Siegel EG, Allen RC, Eaton RP, Ebert R, Creutzfeldt W. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 63:492–8, 1986.
Nauck MA, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29:46–52, 1986.
Adachi T, Tanaka T, Takemoto K, Koshimizn TA, Hirasawa A, Tsujimoto G. Free fatty acids administered into the colon promote the secretion of glucagons-like peptide-1 and insulin. Biochem Biophys Res Commun 340:332–7, 2006.
Partriti A, Facchiano E, Annetti C, Aisa MC, Galli F, Fanelli C, Donini A. Early improvement of glucose tolerance after ileal transposition in a non-obese type 2 diabetes rat model. Obes Surg 15:1258–64, 2005.
Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg 239:1–11, 2004.
Rubino F, Forgione A, Cummings D, Vix M, Gnuli D, Mingrone G, Castagneto M, Marescaux J. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the roximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg 244:741–9, 2006.
Laferrère B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, Kovack B, Bawa B, Koshy N, Lee H, Yapp K, Olivan B. 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 93:2479–85, 2008.
Huang QW, Zhang ZL. Study of distribution on GnRH immunity activity cell and nerves in gastroenteropancreatic system. Acta Anatomica Sinica 21:20–30, 1990.
Huang QW, **ang ZH, Meng L. Study of distribution on GnRH mRNA-positive epithelial cells and nerve cells in rat gastroenteropancreatic system. Acta Anatomica Sinica 27:35–7, 1996.
Huang QW, Yao B, Sun L, Pu RL, Wang L, Zhang RQ. Immunohistochemical and in situ hybridization of gonadotropin releasing hormone (GnRH) and its receptor in rat digestive tract. Life Sci 68:1727–34, 2001.
Yao B, Huang QW, Pu RL, Sun L. In situ hybridization study of gonadotropin releasing hormone receptor mRNA in rat digestive tract. Acta Anatomica Sinica 31:248–52, 2000.
Yao B, Huang W, Huang Y, Chui Y, Wang Y, Li H, Pu R, Wan L, Zhang R. A study on the localization and distribution of GnRH and its receptor in rat. Life Sci 72:2895–904, 2003.
Gao B, Ji QH, Huang WQ. Immunohistochemical localization of glucagon, gonadotropin releasing hormone receptor in rat digestive tract. Chinese Journal of Anatomy 27:372–9, 2004.
Smith MR. Osteoporosis and obesity in men receiving hormone therapy for prostate cancer. J Urol 172:S52–6, 2004.
Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab 91:1305–8, 2006.
Palomba S, Russo T, Orio Jr F, Sammartino A, Sbano FM, Nappi C, Colao A, Mastrantonio P, Lombardi G, Zullo F. Lipid, glucose and lomocysteine metabolism in women treated with a GnRH agonist with or without raloxifene. Hum Reprod 19:415–21, 2004.
Tietz NW. Textbook of clinical chemistry. New York: Saunders; 1986.
Mello de Mello MA, de Souza CT, Braga LR, dos Santos JW, Ribeiro IA, Gobatto CA. Glucose tolerance and insulin action in monosodium glutamate (MSG) obese exercise-trained rats. Physiol Chem Phys Med NMR 33:63–71, 2001.
Portha B. Programmed disorders of beta-cell development and function as one cause for type 2 diabetes? The GK rat paradigm. Diabetes Metab Res Rev 21:495–504, 2005.
Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 87: 1409–39, 2007.
Gautier JF, Fetita S, Sobngwi E, Salaun-Martin C. Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. Diabetes Metab 31:233–42, 2005.
Bojanowska E. Physiology and pathophysiology of glucagon-like peptide-1 (GLP-1): the role of GLP-1 in the pathogenesis of diabetes mellitus, obesity, and stress. Med Sci Monit 11:RA271–8, 2005.
Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, Barakat HA, deRamon RA, Israel G, Dolezal JM, Lynis D. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 222:339–50, 1995.
Pories WJ, Albrecht RJ. Etiology of type II diabetes mellitus: role of the foregut. World J Surg 25:527–31, 2001.
Rubino F, Gagner M. Potential of surgery for curing type 2 diabetes mellitus. Ann Surg 236:554–9, 2002.
Rubino F. Is type 2 diabetes an operable intestinal disease? A provocative yet reasonable hypothesis. Diabetes Care 31: S290–6, 2008.
Ansari MA, Dhar M, Spieker S. Modulation of diabetes with gonadotropin-releasing hormone antagonists in the nonobese mouse model of autoimmune diabetes. Endocrinology 145:337–42, 2004.
Klier M, Schusdziarra V, Pfeiffer EF. Effect of luteinizing hormone-releasing hormone upon insulin release from rat islets in vitro. FEBS Lett 121:363–4, 1980.
Acknowledgements
This work was supported by a grant of the National Natural Science Foundation of China (30870948) “Eleventh five-year plan AIDS and viral hepatitis prevention and treatment of infectious diseases and other major special major science and technology”—Early-Warning System for Tuberculosis (no. 2008ZX100(03-008)) and Investigation on Methodology for Estimation and Prediction of HIV/AIDS Epidemic (no. 2008ZX10100(01-003)).
Conflict of interest statement
We declare that we have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Li Wang and **g Wu equally contributed to this work.
Rights and permissions
About this article
Cite this article
Wang, L., Wu, J., Cao, H. et al. The Correlation Between Intestinal Gonadotropin-Releasing Hormone (GnRH) and Proglucagon in Hyperlipidemic Rats and Goto-Kakizaki (GK) Rats. Endocr Pathol 20, 227–234 (2009). https://doi.org/10.1007/s12022-009-9086-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12022-009-9086-y