Molecular and Cellular Biochemistry

, Volume 293, Issue 1–2, pp 9–14 | Cite as

Increased PC-1 phosphodiesterase activity and inhibition of glucose uptake in adipocytes of type 2 diabetic rats

  • Karlene Barrett
  • Donovan McGrowder
  • Paul Brown
  • Dalip Ragoobirsingh


This study was designed to understand the cellular mechanisms responsible for defects in the insulin-stimulated signal transduction pathway in a type 2 diabetic animal model. We examined the in vitro PC-1 phosphodiesterase activity and glucose uptake in adipose tissue of streptozotocin (STZ)-induced type 2 diabetic rats. The PC-1 activity was significantly increased in adipose tissue of diabetic rats (0.54 ± 0.08 nmol PNTP hydrolyzed/mg protein/min) compared with controls (0.29 ± 0.05 nmol PNTP hydrolyzed/mg protein/min, p < 0.05). Upon insulin stimulation (100 nM), glucose uptake in the adipose tissue of the controls (4.17 ± 1.28×10−8 μmol/mg/min) was significantly higher than that in the diabetic rats (1.26 ± 0.35×10−8; p < 0.05). These results suggest that elevated PC-1 phosphodiesterase activity and decreased glucose uptake in adipose tissues may be acquired characteristics contributing to the development of type 2 diabetes mellitus.

Key Words

adipocytes glucose uptake PC-1 phosphodiesterase activity type 2 diabetes 


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  1. 1.
    DeFronzo RA, Bonadonna RC, Ferrannini E: Pathogenesis of NIDDM: a balanced overview. Diabetes Care 15: 318–368, 1992PubMedGoogle Scholar
  2. 2.
    Kahn CR: Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes 43: 1066–1084, 1994PubMedGoogle Scholar
  3. 3.
    Belli SI, Goding JW: Biochemical characterization of human PC-1 (alkaline phosphodiesterase I). Eur J Biochem 226: 433–443, 1994PubMedCrossRefGoogle Scholar
  4. 4.
    Maddux BA, Sbraccia P, Kumakura S, Sasson S, Youngren JF, Fisher A, Spencer S, Grupe A, Henzel W, Stewart TA, Reaven GM, Goldfine ID: Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus. Nature 373: 448–451, 1995PubMedCrossRefGoogle Scholar
  5. 5.
    Maddux BA, Goldfine ID: PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha subunit. Diabetes 49: 13–19, 2000PubMedGoogle Scholar
  6. 6.
    Stefan C, Wera S, Stalmans W, Bollen M: The inhibition of the insulin receptor by the receptor protein PC-1 is not specific and results from the hydrolysis of ATP. Diabetes 45: 980–983, 1996PubMedGoogle Scholar
  7. 7.
    Ploug T, vonDeurs B, Ai H, Cushman SW, Ralston E: Analysis of GLUT4 distribution in whole skeletal muscle fibres: identification of distinct storage compartments that are reduced by insulin and muscle contractions. J Cell Biol 142: 1429–1446, 1998PubMedCrossRefGoogle Scholar
  8. 8.
    Friedman JE, Dohm GL, Leggett-Frazier N, Elton CW, Tapscott EB, Pories WJ, Caro JF: Restoration of insulin responsiveness in skeletal muscle of morbidly obese patients after weight loss: effect on muscle glucose transport and glucose transporter GLUT-4. J Clin Invest 89: 701–705, 1992PubMedGoogle Scholar
  9. 9.
    Virkamaka A, Ueki K, Khan CR: Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance. J Clin Invest 103: 931–943, 1999Google Scholar
  10. 10.
    McGrowder D, Ragoobirsingh D, Dasgupta T: Decreased insulin binding to mononuclear leucocytes and erythrocytes from dogs after S-nitroso-N-acetylpenicillamine administration. BMC Biochem 3: 1, 2002Google Scholar
  11. 11.
    Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, Novelli M, Ribes G: Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes 47: 224–229, 1998PubMedGoogle Scholar
  12. 12.
    World Health Organization (WHO): Definition, diagnosis and classification of diabetes mellitus Part 1: diagnosis and classification of diabetes mellitus. Department of non-communicable disease surveillance. Geneva: 1999Google Scholar
  13. 13.
    Marette A, Mauriege P, Marcotte B, Algie C, Bouchard C, Theriault G, Bukowiecki LJ, Marceau P, Biron S, Nadeau A, Despres JP: Regional variation in adipose tissue insulin action and GLUT4 glucose transporter expression in severely obesed premenopausal women. Diabetologia 40: 590–598, 1997PubMedCrossRefGoogle Scholar
  14. 14.
    Youngren JF, Maddux BA, Sasson S, Sbraccia P, Tapscott EB, Swanson MS, Dohm GL, Goldfine ID: Skeletal muscle content of membrane glycoprotein PC-1 in obesity. Diabetes 45: 1324–1328, 1996PubMedGoogle Scholar
  15. 15.
    Bradford MM: A rapid and sensitive method for the quantification of microgram quantities of protein, utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254, 1976PubMedCrossRefGoogle Scholar
  16. 16.
    Kahn CR: Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes 43: 1066–1084, 1994PubMedGoogle Scholar
  17. 17.
    Olefsky JM, Nolan JJ: Insulin resistance and non-insulin-dependent diabetes mellitus: cellular and molecular mechanism. Am J Clin Nutr 61(Suppl 1): 980S–986S, 1995.PubMedGoogle Scholar
  18. 18.
    Pedersen O: Genetics of insulin resistance. Exp Clin Endocrinol Diabetes 107: 113–118, 1999PubMedCrossRefGoogle Scholar
  19. 19.
    Reaven G: Role of insulin resistance in human disease. Diabetes 37: 1595–1607, 1988.PubMedGoogle Scholar
  20. 20.
    Taylo SI: Insulin resistance or insulin deficiency: which is the primary cause of NIDDM? Diabetes 43: 735–740, 1994Google Scholar
  21. 21.
    Frittitta L, Youngren J, Vigneri R, Maddux BA, Trischitta V, Goldfine ID: PC-1 content in skeletal muscle of non-obese, non-diabetic subjects: relationship to insulin receptor tyrosine kinase and whole body insulin sensitivity. Diabetologia 39: 1190–1195, 1996PubMedGoogle Scholar
  22. 22.
    Sakoda H, Ogihara T, Anai M, Funaki M: No correlation of plasma cell-1 overexpression with insulin resistance in diabetic rats and 3T3-L1 adipocytes. Diabetes 48: 1365–1371, 1999PubMedGoogle Scholar
  23. 23.
    Kumakura S, Maddux BA, Sung CK: Overexpression of membrane glycoprotein PC-1 can influence insulin action at a post-receptor site. J Cell Biochem 68: 366–377, 1998PubMedCrossRefGoogle Scholar
  24. 24.
    Mora S, Pessin JE: An adipocentric view of signaling and intracellular trafficking. Diabetes Metab Res Rev 18: 345–356, 2002PubMedCrossRefGoogle Scholar
  25. 25.
    Jhun BH, Raampal AL, Liu H, Lachaal M, Jung CY: Effects of insulin on steady state kinetics of GLUT4 subcellular distribution in rat adipocytes. Evidence of constitutive GLUT4 recycling. J Biol Chem 267: 17710–17715, 1992PubMedGoogle Scholar
  26. 26.
    Slot JW, Geuze HJ, Gigengack S, James DE, Lienhard GE.: Translocation of the glucose transporter GLUT4 in cardiac myocytes of the rat. Proc Natl Acad Sci USA 88: 7815–7819, 1991Google Scholar
  27. 27.
    Yang J, Holman GD: Comparison of GLUT4 and GLUT1 subcellular trafficking in basal and insulin-stimulated 3T3-L1 cells. J Biol Chem 268: 4600–4603, 1993PubMedGoogle Scholar
  28. 28.
    Kobayashi M, Olefsky JM: Effects of streptozotocin-induced diabetes on insulin binding, glucose transport, and intracellular glucose metabolism in isolated rat adipocytes. Diabetes 28: 87–95, 1979PubMedGoogle Scholar
  29. 29.
    Rothman DL, Schulman RG, Schulman GI: 31P nuclear magnetic resonance measurements of muscle glucose-6-phosphate: evidence for reduced insulin-dependent muscle glucose transport or phosphorylation activity in non-insulin-dependent diabetes mellitus. J Clin Invest 89: 1062–1075, 1992CrossRefGoogle Scholar
  30. 30.
    Krook A, Roth RA, Jiang XJ, Zierath JR, Wallberg-Henriksson H: Insulin-stimulated Akt kinase activity is reduced in skeletal muscle from non-insulin-dependent diabetic subjects. Diabetes 47: 1281–1286, 1998PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Karlene Barrett
    • 1
  • Donovan McGrowder
    • 2
  • Paul Brown
    • 1
  • Dalip Ragoobirsingh
    • 1
    • 3
  1. 1.Departments of Basic Medical Sciences (Biochemistry Section)University of the West IndiesJamaica
  2. 2.Departments of PathologyUniversity of the West IndiesJamaica
  3. 3.Department of Basic Medical Sciences (Biochemistry Section)University of the West IndiesJamaicaWest Indies

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