Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 May;75(5):1666–1670. doi: 10.1172/JCI111874

Diarrhea in streptozocin-treated rats. Loss of adrenergic regulation of intestinal fluid and electrolyte transport.

E B Chang, R M Bergenstal, M Field
PMCID: PMC425509  PMID: 2987308

Abstract

Diarrhea was noted in rats with streptozocin-induced chronic diabetes. We have investigated the possibility that this diarrhea is a consequence of altered neuronal control of water and electrolyte absorption in the intestinal epithelium. In particular, we examined noradrenergic control because alpha-2-adrenergic agonists are known to stimulate intestinal fluid absorption. When compared with nondiabetic littermates, chronically diabetic rats exhibited significant impairment of fluid absorption by the ileum and colon, but not the jejunum. This impairment of intestinal fluid absorption was not found in either insulin-treated or untreated acutely diabetic (7 d) animals. Mucosal histology appeared normal in all of the above groups. Mucosal norepinephrine stores in the jejunum and ileum of chronically diabetic rats were estimated in vitro by the short-circuit current (Isc) response to tyramine, an agent that effectively releases stored norepinephrine. Pargyline was added to inhibit enzymatic destruction of the added tyramine. In chronically diabetic rats, the Isc response to tyramine was significantly decreased in ileum, but not in jejunum. However, when these responses were expressed as a fraction of the maximal Isc tissue response to exogenously added epinephrine, significant decreases were noted in both ileum and jejunum. In tissues from acutely diabetic rats, Isc responses to tyramine and epinephrine were no different from controls. When sympathetic denervation was produced in nondiabetic rats by treatment with 6-OH-dopamine, the pattern of impaired fluid absorption that developed was the same as that observed in chronically diabetic rats. We conclude that impaired intestinal mucosal absorption of fluid and electrolytes slowly develops in rats made diabetic with streptozocin and that this absorptive impairment is due to a loss of normally present noradrenergic innervation of enterocytes.

Full text

PDF
1666

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BENNETT W. A., BERGE K. G., SPRAGUE R. G. The intestinal tract in diabetic diarrhea; a pathologic study. Diabetes. 1956 Jul-Aug;5(4):289–294. doi: 10.2337/diab.5.4.289. [DOI] [PubMed] [Google Scholar]
  2. BINGHAM J. R., INGELFINGER F. J., SMITHWICK R. H. The effects of sympathectomy on the motility of the human gastrointestinal and biliary tracts. Gastroenterology. 1950 May;15(1 1):6–13. [PubMed] [Google Scholar]
  3. Blanc M. H., Rhie F. H., Dunn P. J., Soeldner J. S. The determination of glycosylated hemoglobins in rats using high pressure liquid chromatography. Metabolism. 1981 Apr;30(4):317–322. doi: 10.1016/0026-0495(81)90108-6. [DOI] [PubMed] [Google Scholar]
  4. Chang E. B., Field M., Miller R. J. Enterocyte alpha 2-adrenergic receptors: yohimbine and p-aminoclonidine binding relative to ion transport. Am J Physiol. 1983 Jan;244(1):G76–G82. doi: 10.1152/ajpgi.1983.244.1.G76. [DOI] [PubMed] [Google Scholar]
  5. Chang E. B., Field M., Miller R. J. alpha 2-Adrenergic receptor regulation of ion transport in rabbit ileum. Am J Physiol. 1982 Mar;242(3):G237–G242. doi: 10.1152/ajpgi.1982.242.3.G237. [DOI] [PubMed] [Google Scholar]
  6. Fedorak R. N., Field M., Chang E. B. Treatment of diabetic diarrhea with clonidine. Ann Intern Med. 1985 Feb;102(2):197–199. doi: 10.7326/0003-4819-102-2-197. [DOI] [PubMed] [Google Scholar]
  7. Field M., Fromm D., McColl I. Ion transport in rabbit ileal mucosa. I. Na and Cl fluxes and short-circuit current. Am J Physiol. 1971 May;220(5):1388–1396. doi: 10.1152/ajplegacy.1971.220.5.1388. [DOI] [PubMed] [Google Scholar]
  8. Field M., McColl I. Ion transport in rabbit ileal mucosa. 3. Effects of catecholamines. Am J Physiol. 1973 Oct;225(4):852–857. doi: 10.1152/ajplegacy.1973.225.4.852. [DOI] [PubMed] [Google Scholar]
  9. Gabbay K. H., Sosenko J. M., Banuchi G. A., Mininsohn M. J., Flückiger R. Glycosylated hemoglobins: increased glycosylation of hemoglobin A in diabetic patients. Diabetes. 1979 Apr;28(4):337–340. doi: 10.2337/diab.28.4.337. [DOI] [PubMed] [Google Scholar]
  10. Hensley G. T., Soergel K. H. Neuropathologic findings in diabetic diarrhea. Arch Pathol. 1968 Jun;85(6):587–597. [PubMed] [Google Scholar]
  11. Lincoln J., Bokor J. T., Crowe R., Griffith S. G., Haven A. J., Burnstock G. Myenteric plexus in streptozotocin-treated rats. Neurochemical and histochemical evidence for diabetic neuropathy in the gut. Gastroenterology. 1984 Apr;86(4):654–661. [PubMed] [Google Scholar]
  12. Low P. A., Walsh J. C., Huang C. Y., McLeod J. G. The sympathetic nervous system in diabetic neuropathy. A clinical and pathological study. Brain. 1975 Sep;98(3):341–356. doi: 10.1093/brain/98.3.341. [DOI] [PubMed] [Google Scholar]
  13. MALINS J. M., FRENCH J. M. Diabetic diarrhoea. Q J Med. 1957 Oct;26(104):467–480. [PubMed] [Google Scholar]
  14. Malins J. M., Mayne N. Diabetic diarrhea. A study of thirteen patients with jejunal biopsy. Diabetes. 1969 Dec;18(12):858–866. doi: 10.2337/diab.18.12.858. [DOI] [PubMed] [Google Scholar]
  15. Scarpello J. H., Greaves M., Sladen G. E. Small intestinal transit in diabetics. Br Med J. 1976 Nov 20;2(6046):1225–1226. doi: 10.1136/bmj.2.6046.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Scarpello J. H., Sladen G. E. Diabetes and the gut. Gut. 1978 Dec;19(12):1153–1162. doi: 10.1136/gut.19.12.1153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schedl H. P., Wilson H. D. Effects of diabetes on intestinal growth and hexose transport in the rat. Am J Physiol. 1971 Jun;220(6):1739–1745. doi: 10.1152/ajplegacy.1971.220.6.1739. [DOI] [PubMed] [Google Scholar]
  18. Schedl H. P., Wilson H. D. Effects of diabetes on intestinal growth in the rat. J Exp Zool. 1971 Apr;176(4):487–495. doi: 10.1002/jez.1401760410. [DOI] [PubMed] [Google Scholar]
  19. Schmidt R. E., Nelson J. S., Johnson E. M., Jr Experimental diabetic autonomic neuropathy. Am J Pathol. 1981 May;103(2):210–225. [PMC free article] [PubMed] [Google Scholar]
  20. Tapper E. J. Local modulation of intestinal ion transport by enteric neurons. Am J Physiol. 1983 May;244(5):G457–G468. doi: 10.1152/ajpgi.1983.244.5.G457. [DOI] [PubMed] [Google Scholar]
  21. Whalen G. E., Soergel K. H., Geenen J. E. Diabetic diarrhea. A clinical and pathophysiological study. Gastroenterology. 1969 Jun;56(6):1021–1032. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES