Abstract
The skin cells chiefly depend on carbohydrate metabolism for their energy requirement during cutaneous wound healing. Since the glucose metabolism is greatly hampered in diabetes and this might affect wound repair process. This prompted us to investigate the intermediate steps of energy metabolism by measuring enzyme activities in the wound tissues of normal and streptozotocin-induced diabetic rats following excision-type of cutaneous injury. The activities of key regulatory enzymes namely hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and glucose-6 phosphate dehydrogenase (G6PD) have been monitored in the granulation tissues of normal and diabetic rats at different time points (2, 7, 14 and 21 days) of postwounding. Interestingly, a significant alteration in all these enzyme activities was observed in diabetic rats. The activity of PFK was increased but HK, LDH and CS showed a decreased activity in the wound tissue of diabetics as compared to normal rats. However G6PD exhibited an elevated activity only at early stage of healing in diabetic rats. Thus, the results suggest that significant alterations in the activities of energy metabolizing enzymes in the wound tissue of diabetic rats may affect the energy availability for cellular activity needed for repair process and this may perhaps be one of the factor responsible for impaired healing in these subjects. (Mol Cell Biochem 270: 71–77, 2005)
Similar content being viewed by others
References
Bullough WS: Epithelial repair. In: J.E. Dunphy, W.V. Winkle Jr, (eds). Repair and Regeneration, the Scientific Basis for Surgical Practice. Mc Graw-Hill, New York, 1969 pp 45–48
Im MJC, Hoopes JE: Enzyme activities in the repairing epithelium during wound healing. J Surg Res 10: 173–179, 1970a
Ziboh VA, Wright R, Hsia SL: Effects of insulin on the uptake and metabolism of glucose by rat skin in vitro. Archs Biochem Biophys 146: 93–99, 1971
Gibbins JR: Metabolic requirements for epithelial migration as defined by the use of metabolic inhibitors in organ culture. Exp Cell Res 71: 329–337, 1972
Keast D, Nguyen T, Newsholme EA: Maximal activities of glutaminase, citrate synthase, hexokinase, phosphofructokinase and lactate dehydrogenase in skin of rats and mice at different ages. FEBS 247: 132–134, 1989
Gupta A, Jain GK, Raghubir, R: A time course study for the development of an immunocompromised wound model, using hydrocortisone. J Pharmacol Toxicol 41: 183–187, 1999
Winegrad AI: Does a common mechanism induce the diverse complications of diabetes. Diabetes 36: 396–406, 1987
Fahey TJ, Sadaty A, Jones WG, Barber A, Smoller B, Shires GT: Diabetes impairs the late inflammatory response to wound healing. J Surg Res 50: 308–318, 1991
Loots MA: Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. J Invest Dermatol 111: 850–857, 1998
Nguyen DT, Keast D: Maximal activities of glutaminase, citrate synthase, hexokinase, 6-phosphofructokinase and lactate dehydrogenase in skin of immune-competent Balb/c and immune-deficient Balb/c (nu/nu) mice during wound healing. Int J Biochem 23: 589–593, 1991
Gupta A, Manhas N, Raghubir R: Energy metabolism during cutaneous wound healing in immunocompromised and aged rats. Mol Cell Biochem 259: 9–14, 2004
Supowit SC, Harris BG: Hexokinase from Ascaris suum muscle. In: W.A. Wood (ed). Methods in Enzymology. Academic press, New York, 1966, pp 21–25
Bergmeyer HU, Grassl M, Walter H: Enzymes. In: H.U. Bergmeyer, J. Bergmeyer, M. Grassl (eds). Methods of Enzymatic Analysis. Verlag Chemie, Weinheim, 1983, pp 185–186
Korenber A: Lactate dehydrogenase of muscle. In: S.P. Colowick, N.O. Kaplan, (eds). Methods in Enzymology. Academic Press, New York, 1955, pp 441–444
Shepherd D, Garland P: Citrate synthase from rat liver. In: J.M. Lowenstein, (ed). Methods in Enzymology. Academic press, New York, 1969, pp 11–16
Lohr GW, Waller HD: Glucose-6-phosphate dehydrogenase. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Verlag Chemie, Weinheim, 1974, pp 636–643
Halprin KM, Ohkawara A: Glucose and glycogen metabolism in the human epidermis. J Invest Dermatol 46: 43–50, 1966
Adachi K, Uno H: Pentose phosphate pathway in growing hair follicles. Am J Physiol 37: 381–386, 1968
Hunt TK, Twomey P, Zederfeldt B, Dunphy JE: Respiratory gas tensions and pH in healing wounds. Am J Surg 114: 302–305, 1967
Silver IA: The measurement of oxygen tension in healing tissue. Prog Resp Res 3: 124–128, 1969
Comstock JP, Udenfried S: Effect of lactate on collagen proline hydroxylase activity in cultured L-929 fibroblast. Pro Nat Aca Sci 66: 552–557, 1970
Opit LJ, Savage JP: Glucose metabolism in human skin graft. Aust J Exp Bio Med Sci 39: 601–605, 1961
Ziboh VA: Implications of dietary oils and poly unsaturated fatty acids in the management of cutaneous disorders. Archs Dermatol 125: 241–245, 1989
Ardawi MSM, Newsholme EA: Maximum activities of some enzymes of glycolysis, the tricarboxylic acid cycle and ketone body and glutamine utilization pathways in lymphocytes of the rats. Biochem J 208: 743–748, 1982
Ardawi MSM, Newsholme EA: Metabolism in lymphocytes and its importance in the immune response. Essay Biochem 21: 1–44, 1985
Shukla A, Rasik AM, Patnaik GK: Depletion of reduced glutathione, ascorbic acid, vitamin E and antioxidant defence enzymes in a healing cutaneous wound. Free Rad Res 26: 93–101, 1997
Im MJC, Hoopes JE: Energy metabolism in healing skin wounds. J Surg Res 10: 459–464, 1970b
Im MJC, Freshwater MF, Hoopes JE: Enzyme activities in granulation tissue: Energy for collagen synthesis. J Surg Res 20: 121–125, 1976
Regen DM, Davis WW, Morgan HE, Park CR: The regulation of hexokinase and phosphofructokinase activity in heart muscle. J Biol Chem 239: 43–49, 1964
England PJ, Randle PJ: Effectors of rat-heart hexokinase and the control of rates of glucose phosphorylation in the perfused rat heart. Biochem J 105: 907–914, 1967
Katzen MM, Soderman DD, Wiley CE: Multiple form of hexokinase activities associated with subcellular particulate and soluble fraction of normal and STZ diabetic rats tissue. J Biol Chem 245: 4081–4096, 1970
Purich DL, Fromm HJ, R0udolph FB: The hexokinase: Kinetic, physical and regulatory properties. In: A. Meister (ed). Advances in Enzymology. Wiley, New York, 1973, pp 249–326
Burcelin R, Printz R, Kande J, Assan R, Granner DK, Girard J: Regulation of glucose transporter and hexokinase II expression in tissues of diabetic rats. Am J Physiol 265: E392–E401, 1993
Liu YQ, Tornheim K, Leahy JL: Fatty acid induced ß- cell hypersensitivity to glucose: Increased phosphofructokinase activity and lowered glucose- 6 phosphate content. J Clin Invest 101: 1870–1875, 1998
Liu YQ, Tornheim K, Leahy JL: Shared biochemical properties of glucotoxicity and lipotoxicity in islets decrease citrate synthase activity and increase phosphofructokinase activity. Diabetes 47: 1889–1893, 1998
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gupta, A., Raghubir, R. Energy metabolism in the granulation tissue of diabetic rats during cutaneous wound healing. Mol Cell Biochem 270, 71–77 (2005). https://doi.org/10.1007/s11010-005-5258-3
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11010-005-5258-3