Abstract
The results of our previous studies demonstrated that acute streptozotocin-induced diabetes in rats evoked a decrease in skin collagen content with little effect on glycosaminoglycans (GAG) content. In our present study we employed the model of chronic diabetes in order to check its effect on skin GAG content.
It was found that the skin of diabetic rats showed a significant decrease in almost all the investigated GAGs by 50-70%. The decrease in heparan sulfate content was slight and statistically insignificant. We sought to determine whether the insulin-like growth factor-I (IGF-1) and IGF-binding proteins (IGF-BPs) levels are altered in animals with experimental diabetes and might contribute to the decrease in tissue GAG content. Circulating IGF-I level was found to be reduced in animals with diabetes and significant changes in serum IGF-BPs were observed. The amount of high molecular weight binding proteins (HMW-BPs) was decreased and the content of low molecular weight binding proteins (LMW-BPs), known as IGF-I inactivating substances, markedly increased. Furthermore, diabetic rats demonstrated an increase of skin proteolytic activity. We conclude that the decrease of GAG content in the skin of diabetic rats is a result of three co-existing phenomena: decreased circulating IGFI level, increased plasma content of LMW BPs and increased proteolytic activity of the skin.
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References
Rouslahti E: Proteoglycans in cell regulation. J Biol Chem 264: 13369–13372, 1989
Poole AR: Proteoglycans in health and disease: structures and functions. Biochem J 236: 1–14, 1986
Cole GJ, Burg M: Characterization of a heparan sulfate proteoglycan that copurifies with the neural cell adhesion molecule. Exp Cell Res 182: 4–60, 1989
Cole GJ, Loewy JA, Glaser L: Neuronal cell-cell adhesion depends on interactions of N-CAM with heparin-like molecules. Nature (London) 320: 445–147, 1986
Clowes AW Clowes MM: Kinetics of cellular proliferation after arterial injury. IV Heparin inhibits rat smooth muscle mitogenesis and migration. Circ Res 58: 839–845, 1986
Majack RA, Cloves AW: Inhibition of vascular smooth muscle cell migration by heparin-like glycosaminoglycans. J Cell Physiol 118: 253–256, 1984
Hadley MA, Byers SW, Suarez-Quian CA, Kleinman HK, Dym M: Extracellular matrix regulates Sertoli cell differentiation, testicular cord formation, and germ cell development in vitro. J Cell Biol 101: 1511–1522, 1985
Spray DC, Fujita M, Saez JC, Choi H, Watanabe T, Hertzberg E, Rosenberg LC, Reid LM: Proteoglycans and glycosaminoglycans induce gap junction synthesis and function in primary liver cultures. J Cell Biol 105: 541–551, 1987.
Folkman J, Klaugsbrun M, Sasse J, Wadzinski M, Ingber D, Vlodavsky I: A heparin-binding angiogenic protein-basic fibroblast growth factor — is stored within basement membrane. Am J Pathol 130: 393–400, 1988
Daughaday WH, Hall K, Salmon WD, van den Brand JL van Vyk JJ: On the nomenclature of the somatomedins and insulin- like growth factors. J Clin Endocrinol Metab 65: 1075–1076, 1987
Oyamada I, Palka J, Schalk EM, Takeda K, Peterkofsky B: Scorbutic and fasted guinea pig sera contain an insulin-like growth factor I — reversible inhibitor of proteoglycan and collagen synthesis in chick embryo chondrocytes and adult human skin fibroblasts. Arch Biochem Biophys 276: 86–93, 1990
Hill DJ, Clemmous DR: Similar distribution of insulin-like growth factor binding proteins-1–2–3 in human fetal tissues. Growth Factors 6: 315–326, 1992
Baxter RC: Characterization of the acid-labile subunit of the growth hormone dependent insulin-like growth factor binding protein complex. J Clin Endocrinol Metab 67: 265–272, 1988
Baxter RC, Martin JL: Binding proteins for the insulin-like growth factors: structure, regulation and function. Prog Growth Factor Res 1: 498, 1989
Lamson G, Giudice LC, Rosenfeld RG: Insulin-like growth factor binding proteins: Structural and molecular relationships. Growth Factors 5: 19–28, 1991
Hossenlopp P, Segovia B, Lassarre C, Roghani C, Bredon M, Binoux M: Evidence of enzymatic degradation of insulin-like growth factor binding proteins in the 150 K complex during pregnancy. J Clin Endocrinol Metab 71: 797–805, 1990
Pałka J, Bird, TA, Oyamada I, Peterkofsky B: Similar hormonal changes in sera from scorbutic and fasted (Vitamin C-supplemented) guinea pig, including decreased IGF-I and appearance of an IGF-I reversible mitogenic inhibitor. Growth Factors 1: 147–156, 1989
Pałka J, Bańkowski E, Wolań ska M: Changes in IGF-binding proteins in rats with experimental diabetes. Ann Biol Clin 50: 701–706, 1993
Kemp SF, Hintz RL: The action of somatomedin on glycosaminoglycans synthesis in cultured chick chondrocytes. Endocrinology 106, 744–749, 1980
Wosicki A: Glikozoaminoglikany kosmówki ludzkiej z pierwszego trymestru rozwoju płodowego (in Polish). Gin Pol 45: 1055–1060, 1974
Bitter T, Muir HM: A modified uronic acid carbazole reaction. Anal Biochem 4: 330–334, 1962
Svejcar J, van Robertson W: Micro separation and determination of mammalian acidic glycosaminoglycans. Anal Biochem 18: 333–350, 1967
Carney SL: Proteoglycans. Proteoglycan constituent analytical techniques. The Elson-Morgan assay for hexosamine. In: M.F. Chaplin, J.F. Kennedy (eds). Carbohydrate Analysis. A Practical Approach. JRL Press, Oxford-Washington DC, 1986, pp 97–142
Pałka J, Peterkofsky B: Salt stimulation of serum insulin-like growth factor binding protein activity. Anal Biochem 175: 442–449, 1988
Moses AC, Nissley SP, Short PA, Rechler MM, White RM, Knight AB, Higa OZ: Increased levels of multiplication-stimulating activity, an insulin-like growth factor in fetal rat serum. Proc Natl Acad Sci USA 77: 3649–3656, 1980
Worowski K, Roszkowska W: Solubility and proteolytic susceptibility of native and denatured haemoglobin and casein (in Polish). Acta Polon Pharm 36: 721–728, 1979
Folin D, Ciocalteu V: Tyrosine and tryptophan determination in protein. J Biol Chem 73: 627–631, 1927
Hardouin S, Hossenlopp P, Segovia B, Seurin D, Portolan G, Lassarre C, Binoux M: Heterogeneity of insulin-like growth factor binding proteins and relationship between structure and affinity. 1. Circulating forms in man. Eur J Biochem 170: 121–132, 1987
Kaufmann V, Zapf J, Turetti B: Demonstration of a specific carrier protein of nonsuppressible insulin-like activity in vivo. J Clin Endocrinol Metab 44: 160–168, 1977
Peterkofsky B, Pałka J, Wilson S, Takeda K, Shah V: Elevated activity of low molecular weight insulin-like growth factor-binding proteins in sera of vitamin C-deficient and fasted guinea pigs. Endocrinology 128: 1769–1779, 1991
Ooi GT, Orłowski CC, Brown AL, Becker RE, Unterman TG, Rechler MM: Different tissue distribution and hormonal regulation of messenger RNAs encoding rat insulin-like growth factor-binding proteins-1 and -2. Mol Endocrinol 4: 321–328, 1990
Boni-Schnetzler M, Binz K, Mary JL, Schmid C, Schwander J, Froesch ER: Regulation of hepatic expression of IGF-I and fetal IGF-I binding protein mRNA in streptozotocin — diabetic rats. FEBS Letters 251: 253–256, 1989
Bohley P: Intracellular proteolysis. In: A. Neuberger and K. Brocklehurst (eds). Hydrolytic Enzymes. Elsevier Sci Publ BV, New York-Amsterdam-Oxford, 1987, pp 307–331
Davenport ML, Clemmons DR, Miles MV, Camacho-Hubner C, D'Ercole J, Underwood LE: Regulation of serum insulin-like growth factor-I (IGF-I) and IGF binding proteins during rat pregnancy. Endocrinology 127: 1278–1286, 1990
Guidice LC, Farrel EM, Pham H, Lamson GL, Rosenfeld RG: Insulin- like growth factor binding proteins in maternal serum throughout gestation and in the puerperium: Effects of a pregnancy-associated serum protease activity. J Clin Endocrinol Metab 71: 806–816, 1990
Pałka J, Wróbel K, Bańkowski E: An alternation of IGF-I binding proteins in experimentally-induced diabetes. Appl Biol Commun 1: 173–180, 1991
Campbell PG, Novak JF: Involvement of plasmin system in dissociation of the insulin-like growth factor-binding protein complex. Endocrinology 130: 1401–112, 1992
Robbins KC: Plasmin. Hand Exp Pharmacol 46: 317–336, 1978
Shimasaki S, Shimonaka M, Zhang HP, Ling N: Isolation and molecular characterization of three novel insulin-like growth factor binding proteins (IGF-BP-4.5, and 6). In: E.M. Spencer (ed) Modern Concepts of Insulin-like Growth Factors. Elsevier, New York, 1991, pp 343–358
Unterman TG, Patel K, Mahathre VK, Rajamohan G, Oehler DT, Becker RE: Regulation of molecular weight insulin-like growth factor binding proteins in experimental diabetes mellitus. Endocrinology 126: 261–2624, 1990
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Cechowska-Pasko, M., Pałka, J. & Bańkowski, E. Decrease in the glycosaminoglycan content in the skin of diabetic rats. The role of IGF-I, IGF-binding proteins and proteolytic activity. Mol Cell Biochem 154, 1–8 (1996). https://doi.org/10.1007/BF00248454
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DOI: https://doi.org/10.1007/BF00248454