Summary
The effect of insulin in vivo on the proliferation and cellularity of epididymal adipose tissue of growing rats was investigated. Following the intraperitoneal administration of small amounts of insulin (500 μU/ rat, twice a day), which did not influence the blood sugar level and food intake, it was found that repeated administration of insulin for 48–72 h leads in adipose tissue to an enhanced incorporation of 14C-2-thymidine into DNA and to an increase of the total amount of DNA and RNA in the fat body. The enhanced DNA synthesis in adipose tissue of insulin-treated rats was marked in nuclear DNA and absent in mitochondrial DNA. After fractionation of adipose tissue by collagenase an enhanced DNA synthesis was found in the fraction of adipose and stromavascular cells. Morphological examination of adipose tissue of insulin-treated rats revealed cells in the phase of mitotic division and an increased ratio of fat cells of smaller size. Calculation of the number of cells in the epididymal fat body revealed that, after administration of insulin, the number of adipose and stromavascular cells increased.
Article PDF
Similar content being viewed by others
References
Hirsch, J., Han, P.W.: Cellularity of rat adipose tissue: Effects of growth, starvation and obesity. J. Lipid Res. 10, 77–82 (1969)
Knittle, J.L., Hirsch, J.: Effect of early nutrition on the development of rat epididymal fat pads: Cellularity and metabolism. J. clin. Invest. 47, 2091–2098 (1968)
Kazdová, L., Braun, T., Fábry, P.: Increased DNA synthesis in epididymal adipose tissue of rats refed after a single fast. Metabolism 16, 1174–1176 (1967)
Taylor, A.W., McBean-Hopkins, K.: DNA content of regenerating epididymal fat pads. Growth 35, 341–348 (1971)
Martinsson, A.: Hypertrophy and hyperplasia of human adipose tissue in obesity. Pol. Arch. Med. wewnet. 42, 481–486 (1969)
Gries, F.A., Daweke, H., Liebermeister, H.: Diabetes mellitus bei Fettsucht. Verh. dtsch. Ges. inn. Med. 76, 51–72 (1970)
Herberg, L., Gries, F.A., Hesse-Wortmann, C.: Effect of weight and cell size on hormonal induced lipolysis in New Zealand obese mice and American obese hyperglycemie mice. Diabetologia 6, 300–305 (1970)
Johnson, P.R., Zucker, L.M., Cruce, J.A.F., Hirsch, J.: Cellularity of adipose depots in the genetically obese Zucker rat. J. Lipid Res. 12, 706–714 (1971)
Turkington, R.W.: Hormone-induced synthesis of DNA by mammary gland in vitro. Endocrinology 82, 540–546 (1968)
Younger, L.R., King, J., Steiner, D.F.: Hepatic proliferative response to insulin in severe alloxan diabetes. Cancer Res. 26, 1408–1313 (1966)
Salmon, W.D., Jr., Du Vall, M.R., Thompson, E.Y.: Stimulation by insulin in vitro incorporation of (35S) sulphate and (14C) leucine into protein polysaceharide complexes, (3H) uridine into RNA and (3H) thymidine into DNA of costal cartilage from hypophysectomized rats. Endocrinology 82, 493–499 (1968)
De la Haba, G., Cooper, G.W., Elting, V.: Hormonal requirements for myogenesis of striped muscle in vitro: Insulin and somatotropin. Proc. Soc. exp. Biol. (N. Y.) 56, 1719–1723 (1966)
Salans, L.B., Zarnowski, M.J., Segal, R.: Effect of insulin upon the cellular character of rat adipose tissue. J. Lipid Res. 13, 616–623 (1972)
Hausberger, F.X., Hausberger, B.C.: Composition of adipose tissue in several forms of obesity. Anat. Rec. 127, 305 (1957)
Hollenberg, C.H., Vost, A., Patten, R.L.: Regulation of adipose mass: control of fat cell development and lipid content. Recent Progr. Hormone Res., 26, 463–503 (1970)
Esanu, C., Murakawa, S., Bray, G.A., Raben, M.S.: DNA synthesis in human adipose tissue in vitro. I. Effect of serum and hormones. J. clin. Endocr. 29, 1027–1032 (1969)
Masters, E.M.: Mitotic activity in cultured brown fat cells. Exp. Cell Res. 59, 334–336 (1970)
Rafaelsen, O.J.: Glycogen content of rat diaphragm after intraperitoneal injection of insulin and other hormones. Acta Physiol. scand. 61, 314–322 (1964)
Rafaelsen, O.J., Lauris, V., Renold, A.E.: Localized intraperitoneal action of insulin on rat diaphragm and epididymal adipose tissue in vivo. Diabetes 14, 19–26 (1965)
Kumaresan, P., Turner, C.W.: Effect of graded levels of insulin on feed consumption in normal female rats. Proc. Soc. exp. Biol. (N.Y.) 120, 828–831 (1965)
Malaisse, W., Malaisse-Lagae, F.: Chronic effect of insulin and glucagon upon islet function. Diabetologia 5, 349–352 (1962)
Luft, R., Cerasi, E., Madison, L.L., Von Euler, U.S., Della Casa, L., Roovete, A.: Effect of a small decrease in blood-glucose on plasma-growth hormone and urinary excretion of catecholamines in man. Lancet 1966 VI, 254–256
Ohneda, A., Aguilar-Parada, E., Eisentraut, A.M.: Control of pancreatic glucagon secretion by glucose. Diabetes 18, 1–10 (1969)
Takebe, K., Kunit, H., Sawano, S., Horiuchi, Y., Mashimo, K.: Circadian rhythms of plasma growth hormone and cortisol after insulin. J. clin. Endocr. 12, 1630–1633 (1969)
Kazdová, L., Vrána, A.: Insulin and adipose tissue Cellularity. Horm. Metab. Res. 2, 117–118 (1970)
Brière, N., Isler, H.: Deoxyribonucleic acid labelling after tritiated thymidine injection. Canad. J. Physiol. Pharmacol. 44, 451–454 (1966)
Baugnet-Mahieu, L., Goutier, R.: Reutilization of labelled-thymidine and -iododeoxyuridine for nuclear and mitochondrial DNA synthesis in regenerating rat liver. Arch. Int. Physiol. Biochim. 80, 319–330 (1972)
Bryant, B.J.: The incorporation of tritium from thymidine into proteins of the mouse. J. Cell Biol. 29, 29–36 (1966)
Kazdová, L., Fábry, P., Vrána, A.: Comparison of the specificity of 14C- and 3H-thymidine as a precursor of deoxyribonucleic acid. Physiol. bohemoslov. 21, 89–90 (1972)
Fleck, A., Munro, H.N.: The precision of the ultraviolet absorption measurements in the Schmidt-Thannhauser procedure for nucleic acid estimation. Biochim. biophys. Acta (Amst.) 55, 571–583 (1962)
Rodbell, M.: Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J. biol. Chem. 239, 375–380 (1964)
Angel, A., Sheldon, H.: Adipose cell organelles: isolation morphology and possible relation to intracellular lipid transport. Ann. N.Y. Acad. Sci. 131, 157–176 (1965)
Steele, W.J., Okamura, N., Busch, H.: Prevention of loss of DNA, RNA and protein into lipid solvents. Biochim. biophys. Acta (Amst.) 87, 490–492 (1964)
Schneider, W.C.: Determination of nucleic acid in tissues by pentose analysis. In: Methods in Enzymology (eds. Colowick, S.P., Kaplan, N.O., Vol. 3, pp. 680–684. New York: Academic Press 1957
Schmidt, G., Thannhauser, S.J.: A method for the determination of DNA, RNA and phosphoproteins in animal tissues. J. biol. Chem. 161, 83–98 (1945)
Lowry, O.H., Rosenbrough, N.J., Farr, A.L., Randall, R.J.: Protein measurement with the Folin phenol reagent. J. biol. Chem. 193, 265–275 (1951)
Folch, J., Lees, M., Sloane-Stanley, G.H.: A simple method for the isolation and purification of total lipids from animal tissues. J. biol. Chem. 226, 497–509 (1957)
Hollenberg, C.H., Vost, A.: Regulation of DNA synthesis in fat cells and stromal elements from rat adipose tissue. J. clin. Invest. 47, 2485–2498 (1968)
Mohr, W., Beneke, G.: Age depence of nuclear content of rat adipose cells. Experientia 24, 1052–1053 (1968)
Rabinowitz, M.: Extranuclear DNA. Bull. Soc. Chim. biol. 50, 311–348 (1968)
Wierzbicki, R., Bartkowiak, J.: Kwas dezoksyrybonukleinowy mitochondriach. Postepy Biochem. 9, 577–586 (1966)
Rakow, L., Beneke, G., Mohr, W., Brauchle, I.: Untersuchungen über die Zellvermehrung im weißen Fettgewebe der genetisch adipösen Maus (C 57BL/6J ob/ob). Beitr. Path. 143, 301–311 (1971)
Di Girolamo, M., Skinner, N.S., Hanley, H.G., Sachs, R.G.: Relationship of adipose tissue blood flow to fat cell size and number. Amer. J. Physiol. 220, 932–937 (1971)
Renold, A.E., Marble, A., Fawcett, D.W.: Action of insulin on deposition of glycogen and storage of fat in adipose tissue. Endocrinology 46, 55–66 (1950)
Hausberger, F.X., Hausberger, B.C.: Effect of insulin and cortisone on weight gain, protein and fat content of rats. Amer. J. Physiol. 193, 455–460 (1958)
Redman, R.S., Sreebny, L.M.: Proliferative behavior of differentiating cells in the developing rat parotid gland. J. Cell Biol. 46, 81–87 (1970)
Mazhuga, P.M., Zhitnikov, A.Y., Kharchuk, K.N.: Differentiation and reproduction of cells in chondrogenesis. Anat. Anz. 126, 172–181 (1970)
Pilgrim, Ch.: DNA synthesis and differentiation in developing adipose tissue. Develop. Biol. 26, 69–76 (1971)
Napolitano, L.M.: Observations on the fine structure of adipose cells. Ann. N.Y. Acad. Sci. 131, 34–42 (1965)
Vodovar, N., Desnoyers, F., Flanzy, J.: Depot adipeux mésentérique du porcelet étude morphologique. Ann. Biol. anim. 12, 243–262 (1972)
Kazdová, L., Fábry, P., Vrána, A.: Postnatal development of cellularity of adipose tissue in different strains of rats. Physiol. bohemoslov (in press)
Szepesi, B., Berdanier, C.D.: Time course of the starve-refed response in rats; the possible role of insulin. J. Nutr. 101, 1563–1574 (1971)
Vrána, A., Fábry, P., Braun, T.: Periodic hyperinsulinaemia in meal-fed rats. Physiol. bohemoslov. 18, 498–499 (1966)
Asplund, K.: Effect of postnatal feeding on the functional maturation of pancreatic islet B-cells of neonatal rats. Diabetologia 8, 153–159 (1972)
Braun, T., Kazdová, L., Fábry, P., Lojda, Z., Hromádková, V.: “Meal eating” and refeeding after a single fast as a stimulus for increasing the number of fat cells in abdominal adipose tissue of rats. Metabolism 17, 825 (1968)
Chlouverakis, C., Dade, F.F., Batt, R.A.L.: Glucose tolerance and time sequence of adiposity, hyperinsulinaemia and hyperglycemia in obese hyperglycemic mice. Metab. clin. Exp. 19, 687–693 (1970)
Zucker, L.M., Antoniades, H.N.: Insulin and fattening in the genetically obese hyperlipemic rat “Fatty”. Fed. Proc. 29, 379 (1970) (Abstr.)
Kazdová, L., Fábry, P., Braun, T.: Composition of diet and response of adipose tissue to refeeding. Physiol. bohemoslov. 17, 569 (1968)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kazdová, L., Fábry, P. & Vrána, A. Effect of small doses of insulin in vivo on the proliferation and cellularity of adipose tissue. Diabetologia 10, 77–83 (1974). https://doi.org/10.1007/BF00421417
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00421417