Skip to main content
SpringerLink
Log in

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

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. DeFronzo RA, Bonadonna RC, Ferrannini E: Pathogenesis of NIDDM: a balanced overview. Diabetes Care 15: 318–368, 1992

    PubMed  CAS  Google Scholar 

  2. Kahn CR: Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes 43: 1066–1084, 1994

    PubMed  CAS  Google Scholar 

  3. Belli SI, Goding JW: Biochemical characterization of human PC-1 (alkaline phosphodiesterase I). Eur J Biochem 226: 433–443, 1994

    Article  PubMed  CAS  Google Scholar 

  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, 1995

    Article  PubMed  CAS  Google Scholar 

  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, 2000

    PubMed  CAS  Google Scholar 

  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, 1996

    PubMed  Google Scholar 

  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, 1998

    Article  PubMed  CAS  Google Scholar 

  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, 1992

    PubMed  CAS  Google Scholar 

  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, 1999

    Google Scholar 

  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, 2002

    Google Scholar 

  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, 1998

    PubMed  CAS  Google Scholar 

  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: 1999

  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, 1997

    Article  PubMed  CAS  Google Scholar 

  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, 1996

    PubMed  CAS  Google Scholar 

  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, 1976

    Article  PubMed  CAS  Google Scholar 

  16. Kahn CR: Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes 43: 1066–1084, 1994

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  18. Pedersen O: Genetics of insulin resistance. Exp Clin Endocrinol Diabetes 107: 113–118, 1999

    Article  PubMed  CAS  Google Scholar 

  19. Reaven G: Role of insulin resistance in human disease. Diabetes 37: 1595–1607, 1988.

    PubMed  CAS  Google Scholar 

  20. Taylo SI: Insulin resistance or insulin deficiency: which is the primary cause of NIDDM? Diabetes 43: 735–740, 1994

    Google Scholar 

  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, 1996

    PubMed  CAS  Google Scholar 

  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, 1999

    PubMed  CAS  Google Scholar 

  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, 1998

    Article  PubMed  CAS  Google Scholar 

  24. Mora S, Pessin JE: An adipocentric view of signaling and intracellular trafficking. Diabetes Metab Res Rev 18: 345–356, 2002

    Article  PubMed  CAS  Google Scholar 

  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, 1992

    PubMed  CAS  Google Scholar 

  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, 1991

    Google Scholar 

  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, 1993

    PubMed  CAS  Google Scholar 

  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, 1979

    PubMed  CAS  Google Scholar 

  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, 1992

    Article  Google Scholar 

  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, 1998

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Basic Medical Sciences (Biochemistry Section), University of the West Indies, Mona, Kingston 7, Jamaica

    Karlene Barrett, Paul Brown & Dalip Ragoobirsingh

  2. Departments of Pathology, University of the West Indies, Mona, Kingston 7, Jamaica

    Donovan McGrowder

  3. Department of Basic Medical Sciences (Biochemistry Section), University of the West Indies, Mona Campus, Kingston 7, Jamaica, West Indies

    Dalip Ragoobirsingh

Authors
  1. Karlene Barrett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Donovan McGrowder
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dalip Ragoobirsingh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dalip Ragoobirsingh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barrett, K., McGrowder, D., Brown, P. et al. Increased PC-1 phosphodiesterase activity and inhibition of glucose uptake in adipocytes of type 2 diabetic rats. Mol Cell Biochem 293, 9–14 (2006). https://doi.org/10.1007/s11010-006-0387-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-006-0387-x

Key Words

Search

Navigation