Hiperglikemia Tidak Menyebabkan Perubahan Bobot Badan dan Jumlah Neuron Mienterik Nitrergik Usus Halus Tikus Wistar (Rattus norvegicus)


Amelia Hana(1*), Pudji Astuti(2), Yuda Heru Fibrianto(3), Sarmin Sarmin(4), Claude Mona Airin(5), Tauhid Tauhid(6)

(1) Fakultas Kedokteran Hewan Universitas Gadjah Mada, Yogyakarta
(2) Fakultas Kedokteran Hewan Universitas Gadjah Mada, Yogyakarta
(3) Fakultas Kedokteran Hewan Universitas Gadjah Mada, Yogyakarta
(4) Fakultas Kedokteran Hewan Universitas Gadjah Mada, Yogyakarta
(5) Fakultas Kedokteran Hewan Universitas Gadjah Mada, Yogyakarta
(6) Fakultas Kedokteran Hewan Universitas Gadjah Mada, Yogyakarta
(*) Corresponding Author


Digestive dysfunction is a common symptom of diabetes. Diabetes can lead to the loss of enteric neurons as well as nerve dysfunction and gastrointestinal complications. There has been no complete report of mienteric nitrergic of small intestines on hyperglycaemia condition, so the purpose of this study was to assess changes of nitrergic neural profile of small intestines on hyperglycemic Wistar strain rats (Rattus norvegicus). Twelve rats were adapted for 3 days, then they were randomly divided into 3 groups namely group I (K-1, as control), group II (K-2), and group III (K-3). Before treatment all rats were fasted for 12 hours, rats K-1 were induced with 1.0 ml of buffer citrate single peritoneal dose; rats K-2 were induced with 40 mg streptozotocin (STZ)/ kg body weight of single peritoneal dose; and rats K-3 were induced with 45 mg STZ /kg body weight of single peritoneal dose. On the 1st and 5th days after STZ induction, blood was collected through the coccigea vein to measure blood glucose levels and weigh the weight. On the day 5th the rats were uthanated with a high dose of ketamine, dissected and taken small intestines (duodenum, jejunum, and ileum) for staining with Nicotinamide Adenine Dinucleotide Phosphate-diaphorase (NADPH-d). Morphometric changes of nitrergic neurons of the small intestine segments were observed. The results showed that on the 5th day increased blood glucose levels of the K-2 and K-3 groups were significantly higher than K-1 (P <0.01). The weight of three groups did not show any significant improvement difference (P> 0.05). The number of neurons in the duodenum, jejunum and ileum of K-2 group increased higher than that of K-1 and K-3 groups. These results indicate that in hyperglycaemic states, the number of nitrergic neurons increases (K-2 group), and there is a significant decrease in the number of neurons (group K-3) compared with K-1 and K-2 groups (P <0.01). The results of this study concluded, that the STZ induction treatment causes hyperglycemia. Hyperglycemia does not affect to the body weight and the number of  nitrergic neurons of small intestines in Wistar strain rats (Rattus norvegicus).


Rat; Streptozotocin; Hyperglycemia; Small intestine; Nitrergic neurons

Full Text:



Akbarzadeh, A.D., Norouzian, M.R., Mehrabi, S.h., Jamshidi, A., Farhangi, A.A., Verdi, S.M.A., Mofidian, and B.L. Rad. 2007. Induction of Diabetes By Streptozotocin In Rats. J.Clin. Biochemistry. 22(2)60-64.

Anitha, M., Gondha, C., Sutliff, R., Parsadanian, A., Mwangi, S., Sitaraman, S.V., and Srinivasan, S. 2006. GDNF Rescues Hyperglycemia-Induced Diabetic Enteric Neuropathy Throught Activation of The P13K/AKT Pathway. J.Clin.Invest. 116(2):344-56. Abstract

Bagyanszki, M. And Bodi, N. 2012. Diabetes-Related Alterations In The Enteric Nervous System And Its Microenvironment. World. Diabetes. 3(5):80-93

Cellek, S., N.A. Foxwell and S. Moncada, 2003. Two phases of nitrergic neuropathy in streptozotocin-induced diabetic rats. Diabetes, 52: 2353-2362. DOI: 10.2337/diabetes.52.9.2353; PMID 12941776.

Dawson, V.L., 1995. Nitric oxide: Role in neurotoxicity. Clin. Exp. Pharmacol. Physiol., 22: 305-308. DOI: 10.1111/j.1440-1681.1995.tb02005.x.

Demedts, I., Masaoka, T., Kindt. S., De Hertogh, G., Geboes, K., Farr, R., Berghe, P.V., and Tack, J. 2013. Gastrointestinal Motility Changes and Myenteric Plexus Alterations In Spontaneously Diabetic Biobreeding Rats. J. Neurogastroenterol Motil. 19(2):161-170.

Fregonesi, C.E.P.T, Miranda-Neto, M.H., Molinari, S.L., and Zanoni, J.N. 2001. Quantitative Study of The Myenteric Plexus of The Stomach of Rats With Streptozotocin-Induced Diabetes. Arq. Neuropsiquiatr. 59(1):50-53.

James, P., and McFadden, R. 2004. Understanding The Processes Behind The Regulation of Blood Glucose. 100(16):56-58. Pdf. https://www.nursingtimes.net

Lee, H.S. and Y.S. Nam, 2006. Immunohistochemical localization of calcium binding proteins and some neurotransmitters in myenteric plexus of goat stomach. J. Vet. Sci., 7: 315-319. DOI: 10.4142/jvs.2006.7.4.315; PMID 17106220.

Miranda NMH, Fregonesi CEPT, Molinari SL, Alves AMP , Defani MA, Zanoni JN, Bazotte RB. 2004. Evaluation of The Nitrergic Myenteric Neurons in The Distal Colon of Diabetic Rats Treated With Acetyl-l-Carnitine. J Morphol Sci 21 (2): 105-110

Neto, M.H.M., Fregonesi, C.E.P.T., Molinari, S.L., Alves, A.M.P., Defani, M.A., Zanoni, J.N., Bazotte, R.B. 2004. Evaluation of The Nitrergic Neurons In The Distal Colon of Diabetic Rats Treated With Acetyl_L-Carnitine. Braz.J.moephol.Sci. 21(2):105-110.

Neunlist, M., P. Aubert, C. Toquet, T. Oreshkova, J. Barouk, P.A. Lehur, M. Schemann and J.P. Galmiche, 2003. Changes in chemical coding of myenteric neurones in ulcerative colitis. Gut, 52: 84-90. DOI: 10.1136/gut.52.1.84; PMID PMC1773507.

Oliveira, J.M.A. and J. Gonçalves, 2010. Guanylate cyclase regulates ileal longitudinal muscle contractions induced by neurogenic nitrergic activity in the rat. Clin. Exp. Pharmacol. Physiol., 37: 375-377. DOI: 10.1111/j.1440-1681.2009.05271.x; PMID 19671068.

Pereira, M.A.S., Liberati, A.P., Souza, I.D.S, and Zanoi, J.N. 2009. Density and Morphometry of Overall Myenteric Neurons opulation From The Duodenum of Diabetic Rats (Rattus norvegicus) Under Ascorbic Acid Supplementation. Int. J. Morphol., 27(2):413-418.

Ramos-Vara, J.A., 2005. Technical aspects of immunohistochemistry. Vet. Pathol., 42: 405-426. DOI: 10.1354/vp.42-4-405; PMID 16006601.

Schmidt, R.E., 2001. Neuronal preservation in the sympathetic ganglia of rats with chronic streptozotocin-induced diabetes. Brain Res., 921: 256-259. DOI: 10.1016/S0006-8993(01)03155-9; PMID 11720733.

Semra, Y.K., M. Wang, N.J. Peat, N.C. Smith, H.R. Shotton and J. Lincoln, 2006. Selective susceptibility of different populations of sympathetic neurons to diabetic neuropathy in vivo is reflected by increased vulnerability to oxidative stress in vitro. Neurosci. Lett., 407: 199-204. DOI: 10.1016/j.neulet.2006.08.045; PMID 16973273.

Semra, Y.K., N.C. Smith and J. Lincoln, 2004. Comparative effects of high glucose on different adult sympathetic neurons in culture. Neuroreport, 15: 2321-2325. DOI: 10.1097/00001756-200410250-00004; PMID 15640748.

Silverio, S.M., Mari, R.B., Clebis, N.K., Scoz, J.R., Germano, R.M., Agreste, F., Bombonato, P.P., and Stabille, S.R. 2008. Assessment of NADPH-Diaphorase Stained Myenteric Neurons of The Jejunum of Diabetic Rats Supplemented With Ascorbic Acid. J. Pesq.Vet.Bras. 28(2)

Skundric, D.S., and Lisak, R.P. 2003. Role of Neuropoietic Cytokines in Development and Progression of Diabetic Polyneuropathy : Fom Glucose Metabolism to Neurodegeneration. Exp Diabesity Res. 4(4),303-12.

Tolkovsky, A., 2002. Apoptosis in diabetic neuropathy. Int. Rev. Neurobiol., 50: 145-159. DOI: 10.1016/S0074-7742(02)50076-3; PMID 12198809.

Watkins, C.C., A. Sawa, S. Jaffrey, S. Blackshaw, R.K. Barrow, S.H. Snyder and C.D. Ferris, 2000. Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy. J. Clin. Invest., 106: 373-384. DOI: 10.1172/jci8273; PMID 10930440.

Zafar, M. And Naqvi, S.N.H. 2010. Effect of STZ-Induced Diabetes on The Relative Weights of Kidney, Liver and Pancreas InAlbino Rats : A Comparative Study. Int. J. Morphol., 28(1)135-142.

Zanoni, J.N., Pereira, P.G.C and Pereira, M.A.S. 2009. Analysis of Myenteric Neurons of The Cecum of Diabetic Rats After Supplementation With Ascorbic Acid. Int. J. Morphol. 27(2):387-392.

DOI: https://doi.org/10.22146/jsv.38409

Article Metrics

Abstract views : 2269 | views : 1686


  • There are currently no refbacks.

Copyright (c) 2018 Jurnal Sain Veteriner

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Jurnal Sain Veteriner Indexed by


Copyright of JSV (Jurnal Sain Veteriner) ISSN 0126-0421 (print), ISSN 2407-3733 (online).

Fakultas Kedokteran Hewan, Universitas Gadjah Mada

Jl. Fauna No.2, Karangmalang, Yogyakarta

Phone: 0274-560862

Fax: 0274-560861

Email: jsv_fkh@ugm.ac.id

HP. 0895363078367

Jurnal Sain Veteriner is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.


web stats View My Stats