Abstract
In the present study, the effect of streptozotocin-induced diabetes on the cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) enteric nervous structures was investigated within the porcine stomach. To induce diabetes, the pigs were administered intravenously streptozotocin at a dose of 150 mg/kg of body weight. A significant decrease of the number of CART-LI perikarya was observed in the myenteric plexus of the gastric antrum, corpus, and pylorus in the experimental group. In contrast, submucous plexus was devoid of CART-positive neuronal cells both in control and experimental animals. In the control group, the highest densities of CART-LI nerve fibers were observed in the circular muscle layer of antrum and slightly less nerve fibers were present in the muscle layer of corpus and pylorus. In turn, submucous layer of all studied stomach regions revealed relatively smaller number of CART-positive nerve fibers. Diabetes caused statistically significant decrease in the expression of CART-LI nerve fibers only in the antrum circular muscle layer. Also, no changes in the CART-like immunoreactivity in the intraganglionic nerve fibers were observed. The obtained results suggest that acute hyperglycemia produced significant reduction of the CART expression in enteric perikarya throughout entire stomach as well as decrease of density the CART-LI fibers in circular muscle layer of the antrum. Additionally, we suggest that CART might be involved in the regulation of stomach function especially in the gastric motility.
Similar content being viewed by others
References
Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15(7):539–553
Ballmann M, Conlon JM (1985) Changes in the somatostatin, substance P and vasoactive intestinal polypeptide content of the gastrointestinal tract following streptozotocin-induced diabetes in the rat. Diabetologia 28(6):355–358
Bannerman PG, Mirsky R, Jessen KR (1997) Analysis of enteric neurons, glia and their interactions using explant cultures of the myenteric plexus. Dev Neurosci 9(4):201–227
Belai A, Burnstock G (1990) Changes in adrenergic and peptidergic nerves in the submucous plexus of streptozocin-diabetic rat ileum. Gastroenterology 98(6):1427–1436
Belai A, Lincoln J, Milner P, Crowe R, Loesch A, Burnstock G (1985) Enteric nerves in diabetic rats: increase in vasoactive intestinal polypeptide but not substance P. Gastroenterology 89(5):967–976
Belai A, Calcutt NA, Carrington AL, Diemel LT, Tomlinson DR, Burnstock G (1996) Enteric neuropeptides in streptozotocin-diabetic rats; effects of insulin and aldose reductase inhibition. J Auton Nerv Syst 58(3):163–169
Bulc M, Gonkowski S, Landowski P, Kamińska B, Całka J (2014) Immunohistochemical distribution of cocaine and amphetamine regulatory peptide-like immunoreactive (CART-LI) nerve fibers in the circular muscle layer and their relationship to other peptides in the human caecum. Acta Histochem 116(6):1029–1036
Burliński PJ (2012) Inflammation- and axotomy-induced changes in cocaine- and amphetamine-regulated transcript peptide-like immunoreactive (CART-LI) nervous structures in the porcine descending colon. Pol J Vet Sci 15(3):517–524
Chandrasekharan B, Srinivasan S (2007) Diabetes and the enteric nervous system. Neurogastroenterol Motil 19(12):951–960
Clerc N, Furness JB (2004) Intrinsic primary afferent neurones of the digestive tract. Neurogastroenterol Motil 16(Suppl 1):24–27
Demedts I, Masaoka T, Kindt S, De Hertogh G, Geboes K, Farré R, Vanden Berghe P, Tack J (2013) Gastrointestinal motility changes and myenteric plexus alterations in spontaneously diabetic biobreeding rats. J Neurogastroenterol Motil 19(2):161–170
Deshpande AD, Harris-Hayes M, Schootman M (2008) Epidemiology of diabetes and diabetes-related complications. Phys Ther 88(11):1254–1264
Douglass J, Daoud S (1996) Characterization of the human cDNA and genomic DNA encoding CART: a cocaine- and amphetamine-regulated transcript. Gene 169(2):241–245
Edwards JL, Vincent AM, Cheng HT, Feldman EL (2008) Diabetic neuropathy: mechanisms to management. Pharmacol Ther 120(1):1–34
Ekblad E (2006) CART in the enteric nervous system. Peptides 27(8):2024–2030
Ekblad E, Kuhar M, Wierup N, Sundler F (2003) Cocaine- and amphetamine-regulated transcript: distribution and function in rat gastrointestinal tract. Neurogastroenterol Motil 15(5):545–557
Ellis LM, Mawe GM (2003) Distribution and chemical coding of cocaine- and amphetamine-regulated transcript peptide (CART)-immunoreactive neurons in the guinea pig bowel. Cell Tissue Res 312(3):265–274
Furlan MM, de Miranda Neto MH, Sant’ana Dde M, Molinari SL (1999) Number and size of myenteric neurons of the duodenum of adult rats with acute diabetes. Arq Neuropsiquiatr 57(3B):740–745
Furness JB (2006) The organisation of the autonomic nervous system: peripheral connections. Auton Neurosci 130(1–2):1–5
Furness JB (2012) The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 69:286–294
Furness JB, Kunze WA, Clerc N (1999) Nutrient tasting and signaling mechanisms in the gut II. The intestine as a sensory organ: neural, endocrine, and immune responses. Am J Physiol 277(5 Pt 1):G922–G928
Gatopoulou A, Papanas N, Maltezos E (2012) Diabetic gastrointestinal autonomic neuropathy: current status and new achievements for everyday clinical practice. Eur J Intern Med 23(6):499–505
Gonkowski S, Całka J (2012) Changes in pituitary adenylate cyclase-activating peptide 27-like immunoreactive nervous structures in the porcine descending colon during selected pathological processes. J Mol Neurosci 48(3):777–787
Gonkowski S, Burliński P, Skobowiat C, Majewski M, Arciszewski MB, Radziszewski P, Całka J (2009) Distribution of cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) nerve structures in the porcine large intestine. Acta Vet Hung 4:509–520
Gonkowski S, Kamińska B, Landowski P, Całka J (2013) Immunohistochemical distribution of cocaine- and amphetamine-regulated transcript peptide - like immunoreactive (CART-LI) nerve fibers and various degree of co-localization with other neuronal factors in the circular muscle layer of human descending colon. Histol Histopathol 7:851–858
Grüssner R, Nakhleh R, Grüssner A, Tomadze G, Diem P, Sutherland D (1993) Streptozotocin-induced diabetes mellitus in pigs. Horm Metab Res 25(4):199–203
Gunnarsdóttir A, Wierup N, Larsson LT, Kuhar MJ, Ekblad E (2007) CART-peptide immunoreactivity in enteric nerves in patients with Hirschsprung’s disease. Eur J Pediatr Surg 17(3):184–189
Jaworski JN, Jones DC (2006) The role of CART in the reward/reinforcing properties of psychostimulants. Peptides 27(8):1993–2004
Jenkinson KM, Reid JJ (2000) Altered non-adrenergic non-cholinergic neurotransmission in gastric fundus from streptozotocin-diabetic rats. Eur J Pharmacol 401(2):251–258
Kasacka I, Piotrowska Z (2012) Evaluation of density and distribution of CART-immunoreactive structures in gastrointestinal tract of hypertensive rats. Biofactors 38(6):407–415
Kasacka I, Piotrowska Z, Car H, Janiuk I, Lebkowski W (2012) Cocaine- and amphetamine-regulated transcript: identification and distribution in human gastrointestinal tract. J Biol Regul Homeost Agents 26(3):419–428
King AJ (2012) The use of animal models in diabetes research. Br J Pharmacol 3:877–894
Lenzen S (2008) The mechanisms of alloxan and streptozotocin inducted diabetes. Diabetologia 51(2):216–226
Palus K, Rytel L (2013) Co-localisation of cocaine- and amphetamine-regulated transcript peptide and vasoactive intestinal polypeptide in the myenteric plexus of the porcine transverse colon. Folia Morphol (Warsz) 72(4):328–332
Rees DA, Alcolado JC (2005) Animal models of diabetes mellitus. Diabet Med 22(4):359–370
Swindle MM, Makin A, Herron AJ, Clubb Jr FJ, Frazier KS (2012) Swine as models in biomedical research and toxicology testing. Vet Pathol 49(4):738
Thomas CC, Philipson LH (2015) Update on diabetes classification. Med Clin N Am 99(1):1–16
Verma N, Rettenmeier AW, Schmitz-Spanke S (2011) Recent advances in the use of Sus scrofa (pig) as a model system for proteomic studies. Proteomics 11(4):776–793
Vicentic A, Jones DC (2007) The CART (cocaine- and amphetamine-regulated transcript) system in appetite and drug addiction. J Pharmacol Exp Ther 320(2):499–506
Wierup N, Sundler F (2006) CART is a novel islet regulatory peptide. Peptides 27(8):2031–2036
Wierup N, Gunnarsdóttir A, Ekblad E, Sundler F (2007) Characterisation of CART-containing neurons and cells in the porcine pancreas, gastro-intestinal tract, adrenal and thyroid glands. BMC Neurosci 8:51
Wojtkiewicz J, Gonkowski S, Bladowski M, Majewski M (2012) Characterization of cocaine- and amphetamine- regulated transcript-like immunoreactive (CART-LI) enteric neurons in the porcine small intestine. Acta Vet Hung 60(3):371–381
Wrzos HF, Cruz A, Polavarapu R, Shearer D, Ouyang A (1997) Nitric oxide synthase (NOS) expression in the myenteric plexus of streptozotocin-diabetic rats. Dig Dis Sci 42(10):2106–2110
Zacharko-Siembida A, Arciszewski MB (2014) Immunoreactivity to cocaine- and amphetamine-regulated transcript in the enteric nervous system of the pig and wild boar stomach. Anat Histol Embryol 43(1):48–55
Acknowledgments
This study was financed by a statutory grant No. 528-0523.0802.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bulc, M., Gonkowski, S. & Całka, J. Expression of Cocaine and Amphetamine Regulated Transcript (CART) in the Porcine Intramural Neurons of Stomach in the Course of Experimentally Induced Diabetes Mellitus. J Mol Neurosci 57, 376–385 (2015). https://doi.org/10.1007/s12031-015-0618-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-015-0618-2