Abstract
Intestinal adaptation at the cellular level was examined in groups of streptozotocin-diabetic and agematched control rats. Small intestines were removed and divided into four segments of roughly equal length. For each segment, epithelial volume, villous and microvillous surface areas and the mean volumes of epithelial cells in crypts and villi were estimated. From these data, we were able to estimate total numbers of epithelial cells in crypts and villi, assess adaptation at the level of the average cell and explore variation along the crypt-villus axis, between segments and between groups. Whilst the villus:crypt cell ratio did not change, diabetic animals contained about 80% more epithelial cells than control rats. The morphophenotype of villous epithelial cells (represented by nuclear volume, cell height, area and volume, and number and surface area of microvilli) was basically the same as that in controls. By contrast, crypt cells and their nuclei were 40–50% bigger in diabetic rats. Significant differences between segments were confined to the numbers and sizes of crypt cells and their nuclei. We conclude that experimental diabetes leads to both proliferative and hypertrophic responses within crypts. Crypt cells become fatter but not taller. Crypt hyperplasia is accompanied by an equiproportionate increase in villous epithelial cells, but these are of essentially normal morphophenotype.
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Abbas B, Hayes TL, Wilson DJ, Carr KE (1989) Internal structure of the intestinal villus: morphological and morphometric observations at different levels of the mouse villus. J Anat 162:263–273
Alison MR, Sarraf CE (1994) The role of growth factors in gastrointestinal cell proliferation. Cell Biol Int 18:1–10
Altmann GG (1990) Renewal of the intestinal epithelium: new aspects as indicated by recent ultrastructural observations. J Electron Microsc Techn 16:2–14
Altmann GG, Enesco M (1967) Cell number as a measure of distribution and renewal of epithelial cells in the intestine of growing and adult rats. Am J Anat 121:319–336
Baddeley AJ, Gundersen HJG, Cruz-Orive L-M (1986) Estimation of surface area from vertical sections. J Microsc 142:259–276
Bhoyrul S, Sharma AK, Stribling D, Mirrlees DD, Peterson RG, Farber MO, Thomas PK (1988) Ultrastructural observations on myelinated fibres in experimental diabetes: effect of the aldose reductase inhibitor Ponalrestat given alone or in conjunction with insulin therapy. J Neurol Sci 85:131–147
Both NJ de, Dongen JM van, Hofwegen B van, Keulemans J, Visser WJ, Galjaardt H (1974) The influence of various cell kinetic conditions on functional differentiation in the small intestine of the rat. A study of enzymes bound to sub-cellular organelles. Dev Biol 38:119–137
Brown AL (1962) Microvilli of the human jejunal epithelial cell. J Cell Biol 12:623–627
Burant CF, Flink S, DePaoli AM, Chen J, Lee W-S, Hediger MA, Buse JB, Chang EB (1994) Small intestine hexose transport in experimental diabetes. J Clin Invest 93:578–585
Caspary WF (1973) Effect of insulin and experimental diabetes mellitus on the digestive absorptive function of the small intestine. Digestion 9:248–263
Clarke RM (1970) Mucosal architecture and epithelial cell production rate in the small intestine of the albino rat. J Anat 107:519–529
Clarke RM (1972) The effect of growth and fasting on the number of villi and crypts in the small intestine of the albinorat rat. J Anat 112:27–33
Clarke RM (1977) The effects of age on mucosal morphology and epithelial cell production in rat small intestine. J Anat 123:805–811
Cruz-Orive L-M, Hunzicker EB (1986) Stereology for anisotropic cells: application to growth cartilage. J Microsc 143:47–80
Dongen JM van, Visser WJ, Daems WT, Galjaard H (1976) The relation between cell proliferation, differentiation and ultrastructural development in rat intestinal epithelium. Cell Tissue Res 174:183–199
Elbrønd VS, Dantzer V, Mayhew TM, Skadhauge E (1991) Avian lower intestine adapts to dietary salt (NaCl) depletion by increasing transepithelial sodium transport and microvillous membrane surface area. Exp Physiol 76:733–744
Forgue-Lafitte ME, Marescot MR, Chamblier MC, Rosselin G (1980) Evidence for the presence of insulin binding sites in isolated rat intestinal epithelial cells. Diabetologia 19:373–378
Forrester JM (1972) The number of villi in rat's jejunum and ileum: effect of normal growth, partial enterectomy and tube feeding. J Anat 111:283–291
Galjaard H, Meer-Flieggen W van der, Both NJ de (1972) Cell differentiation in gut epithelium. In: Viza D, Harris H (eds) Cell differentiation. Munksgaard, Copenhagen, pp 322–328
Gallo-Payet N, Hugon JS (1984) Insulin receptors in isolated adult mouse intestinal cells: studies in vivo and in organ culture. Endocrinology 114:1885–1892
Goodlad RA, Lee CY, Gilbey SG, Ghatei MA, Bloom SR (1993) Insulin and intestinal epithelial cell proliferation. Exp Physiol 78:697–705
Gundersen HJG (1979) Estimation of tubule or cylinder Lv, Sv and Vv on thick sections. J Microsc 117:333–345
Gundersen HJG, Jensen EB (1985) Stereological estimation of the volume-weighted mean volume of arbitrary particles observed on random sections. J Microsc 138:127–142
Gundersen HJG, Jensen EB (1987) The efficiency of systematic sampling and its prediction. J Microsc 147:229–263
Hartnell JM, Storrie MC, Mooradian AD (1990) Diabetes-related changes in chromatin structure of brain, liver, and intestinal epithelium. Diabetes 39:348–353
Heinz-Erian P, Kessler U, Funk B, Gais P, Kiess W (1991) Identification and in situ localisation of the insulin-like growth factor II/mannose-6-phosphate (IGF-II/M6P) receptor in the rat gastrointestinal tract: comparison with the IGF-I receptor. Endocrinology 129:1769–1778
Jervis EL, Levin RJ (1966) Anatomic adaptation of the alimentary tract of the rat to the hyperphagia of chronic alloxandiabetes. Nature 210:391–393
Karasov WH, Diamond JM (1983) Adaptive regulation of sugar and amino acid transport by vertebrate intestine. Am J Physiol 245:G443-G462
Keelan M, Walker K, Thompson ABR (1985) Intestinal brush border membrane marker enzymes, lipid composition and villus morphology: effect of fasting and diabetes mellitus in rats. Comp Biochem Physiol 82A:83–89
Laburthe M, Rouyer F, Gammeltoft S (1988) Receptors for insulin-like growth factors I and II in rat gastrointestinal epithelium. Am J Physiol 245:G457-G462
Lal D, Schedl HP (1974) Intestinal adaptation in diabetes: amino acid absorption. Am J Physiol 227:827–831
Leblond CP (1981) The life history of cells in renewing systems. Am J Anat 160:114–158
Levin RJ (1984) Intestinal adaptation to dietary change as exemplified by dietary restriction studies. In: Batt RM, Lawrence TLJ (eds) Function and dysfunction of the small intestine. Liverpool University Press, Liverpool, pp 77–93
Lorenz-Meyer H, Gottesburen H, Menge H, Bloch R, Riecken EO (1974) Intestinal structure and function in relation to blood sugar levels and food intake in experimental diabetes. In: Dowling RH, Riecken EO (eds) Intestinal adaptation. Schattauer, Stuttgart, pp 189–191
Mayhew TM (1990) Striated brush border of intestinal absorptive epithelial cells: stereological studies on microvillous morphology in different adaptive states. J Electron Microsc Techn 16:45–55
Mayhew TM (1991) The new stereological methods for interpreting functional morphology from slices of cells and organs. Exp Physiol 76:639–665
Mayhew TM (1992) A review of recent advances in stereology for quantifying neural structure. J Neurocytol 21:313–328
Mayhew TM, Carson FL (1989) Mechanisms of adaptation in rat small intestine: regional differences in quantitative morphology during normal growth and experimental hypertrophy. J Anat 164:189–200
Mayhew TM, Middleton C (1985) Crypts, villi and microvilli in the small intestine of the rat. A stereological study of their variability within and between animals. J Anat 141:1–17
Mayhew TM, Middleton C, Ross GA (1988) Dealing with oriented surfaces: studies on villi and microvilli of rat small intestine. In: Reith A, Mayhew TM (eds) Stereology and morphometry in electron microscopy. Problems and solutions. Hemisphere, New York, pp 85–98
Mayhew TM, Carson FL, Sharma AK (1989) Small intestinal morphology in experimental diabetic rats: a stereological study on the effects of an aldose reductase inhibitor (ponalrestat) given with or without conventional insulin therapy. Diabetologia 32:649–654
Mayhew TM, Elbrønd VS, Dantzer V, Skadhauge E, Moller O (1992) Structural and enzymatic studies on the plasma membrane domains and sodium pump enzymes of absorptive epithelial cells in the avian lower intestine. Cell Tissue Res 270:577–585
McElligott TF, Beck IT, Dinda PK, Thompson S (1975) Correlation of structural changes at different levels of the jejunal villus with positive and negative net water transport in vivo and in vitro. Can J Physiol Pharmacol 53:439–450
Miller DL, Hanson W, Schedl HP, Osborne JW (1977) Proliferation rate and transit time of mucosal cells in the small intestine of the diabetic rat. Gastroenterology 73:1326–1332
Miller S (1975) Experimental design and statistics. Methuen, London
Nakabou Y, Okita C, Takano Y, Hagiira H (1974) Hyperplastic and hypertrophic changes of the small intestine. J Nutr Sci Vitaminol 20:227–234
Nakabou Y, Ishikawa Y, Misaki A, Hagihira H (1980) Effect of food intake on intestinal absorption and hydrolases in alloxan-diabetic rats. Metabolism 29:181–185
Nordstrom C, Dahlqvist A, Josefsson L (1968) Quantitative determination of enzymes in different parts of the villi and crypts of rat small intestine. J Histochem Cytochem 15:713–721
Olsen WA, Rosenberg IH (1970) Intestinal transport of sugars and amino acids in diabetic rats. J Clin Invest 49:96–105
Olsen W, Agresti HL, Lorentzsonn VW (1974) Intestinal disaccharidases in diabetic rats. In: Dowling RH, Riecken EO (eds) Intestinal adaptation. Schattauer, Stuttgart, pp 179–187
Park JH, Vanderhoof JA, Blackwood D, MacDonald RG (1990) Characterisation of type I and type II insulin-like growth factor receptors in an intestinal epithelial cell line. Endocrinology 126:2998–3005
Pothier P, Hugon JS (1980) Characterization of isolated villus and crypt cells from the small intestine of the adult mouse. Cell Tissue Res 211:405–418
Potten CS (1980) Stem cells in small-intestinal crypts. In: Appleton DR, Sunter JP, Watson AJ (eds) Cell proliferation in the gastrointestinal tract. Pitman Medical, London, pp 141–154
Potten CS, Loeffler M (1987) A comprehensive model of the crypts of the small intestine of the mouse provides insights into the mechanisms of cell migration and the proliferation hierarchy. J Theor Biol 127:381–391
Potten CS, Booth C, Chadwick CA, Evans GS (1994) A potent stimulator of small intestinal cell proliferation extracted by simple diffusion from intact irradiated intestine: in vitro studies. Growth Factors 10:53–61
Schedl HP, Wilson HD (1971) Effects of diabetes on intestinal growth and hexose transport in the rat. Am J Physiol 220:1739–1745
Sokal RR, Rohlf FJ (1981) Biometry. The principles and practice of statistics in biological research. Freeman, San Francisco
Stenling R, Hagg E, Falkmer S (1984) Stereological studies on the rat small intestinal epithelium. III. Effects of short-term alloxan diabetes. Virchows Arch [B] 47:263–270
Tahara T, Yamamoto T (1988) Morphological changes of the villous microvascular architecture and intestinal growth in rats with streptozotocin-induced diabetes. Virchows Archiv [A] 413, 151–158
Weibel ER (1979) Stereological methods, vol 1: Practical Methods for Biological Morphometry. Academic Press, London
Williams M, Mayhew TM (1992) Responses of enterocyte micro-villi in experimental diabetes to insulin and an aldose reductase inhibitor (ponalrestat). Virchows Arch [B] 62:385–389
Wright (1980) Cell proliferation in the normal gastrointestinal tract. Implications for proliferative responses. In: Appleton DR, Sunter JP, Watson AJ (eds) Cell proliferation in the gastrointestinal tract. Pitman Medical, London, pp 3–25
Younoszai MK, Parekh VV, Hoffman JL (1993) Polyamines and intestinal epithelial hyperplasia in streptozotocin-diabetic rats. Proceedings of the Society for Experimental Biology and Medicine 202:206–211
Young GP, Morton CL, Rose IS, Taranto TM, Bhathal PS (1987) Effects of intestinal adaptation on insulin binding to villus cell membranes. Gut 28:57–62
Zoubi SA, Mayhew TM, Sparrow RA (1994) Crypt and villous epithelial cells in adult rat small intestine: numerical and volumetric variation along longitudinal and vertical axes. Epithelial Cell Biol 3:112–118
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Zoubi, S.A., Mayhew, T.M. & Sparrow, R.A. The small intestine in experimental diabetes: cellular adaptation in crypts and villi at different longitudinal sites. Vichows Archiv A Pathol Anat 426, 501–507 (1995). https://doi.org/10.1007/BF00193174
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DOI: https://doi.org/10.1007/BF00193174