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Current diabetes reports
Jun, 2009;9 (3): 215-20.

Thiazolidinediones in prediabetes and early type 2 diabetes: what can be learned about that disease's pathogenesis.

Jack L Leahy
Author Information
  1. Jack L Leahy: Colchester Research Facility, Colchester, VT 05446, USA. jleahy@uvm.edu
PMID: 19490823 DOI: 10.1007/s11892-009-0035-4

Abstract

Several clinical trials have shown a high success rate of thiazolidinediones (TZDs) in prediabetes and early type 2 diabetes. The presumed mechanism of this effect has shifted from the best known effect of these agents to improve insulin sensitivity, to preservation of beta-cell function. The common explanation for this effect is unloading of the islet beta cell from the insulin resistance-induced hyperstimulation that eventually leads to beta-cell failure, so-called beta-cell rest. However, a recent finding is powerful biological effects of peroxisome proliferator-activated receptor (PPAR)gamma signaling in islet beta cells. This article reviews this topic by first describing the TZD intervention studies. Then it provides an overview of the current concepts regarding the beta-cell overwork and rest hypotheses, and the recent information about PPARgamma signaling effects in beta cells.

References

  1. Lancet. 1976 Feb 28;1(7957):444-7 [PMID: 55717]
  2. Diabetes Care. 2009 Jan;32(1):193-203 [PMID: 18945920]
  3. Biochim Biophys Acta. 2007 Aug;1771(8):999-1013 [PMID: 17475546]
  4. Endocrinology. 2003 Aug;144(8):3399-405 [PMID: 12865318]
  5. Diabetes. 2007 Jan;56(1):88-95 [PMID: 17192469]
  6. Diabetes Care. 2008 May;31(5):845-51 [PMID: 18223031]
  7. J Clin Invest. 1988 May;81(5):1407-14 [PMID: 3284912]
  8. N Engl J Med. 2002 Feb 7;346(6):393-403 [PMID: 11832527]
  9. Diabet Med. 2007 Feb;24(2):172-7 [PMID: 17257280]
  10. Diabetes. 2000 Nov;49(11):1840-8 [PMID: 11078450]
  11. N Engl J Med. 2006 Oct 12;355(15):1551-62 [PMID: 16980380]
  12. Diabetes. 2006 Feb;55(2):517-22 [PMID: 16443789]
  13. Metabolism. 1982 Feb;31(2):139-42 [PMID: 7043166]
  14. Diabetologia. 2008 Jul;51(7):1100-10 [PMID: 18504548]
  15. Am J Physiol Endocrinol Metab. 2000 Sep;279(3):E520-8 [PMID: 10950818]
  16. N Engl J Med. 2006 Dec 7;355(23):2427-43 [PMID: 17145742]
  17. Diabetologia. 1980 Jan;18(1):23-8 [PMID: 6988263]
  18. Nat Clin Pract Endocrinol Metab. 2008 Jul;4(7):382-93 [PMID: 18493227]
  19. Prog Lipid Res. 2006 Mar;45(2):120-59 [PMID: 16476485]
  20. Cell. 2005 Dec 16;123(6):993-9 [PMID: 16360030]
  21. J Clin Endocrinol Metab. 2004 Jun;89(6):2846-51 [PMID: 15181067]
  22. Lancet. 2006 Sep 23;368(9541):1096-105 [PMID: 16997664]
  23. Mol Cell Biol. 2003 Oct;23(20):7222-9 [PMID: 14517292]
  24. N Engl J Med. 2004 Sep 9;351(11):1106-18 [PMID: 15356308]
  25. Br Med J. 1976 May 22;1(6020):1252-4 [PMID: 1268654]
  26. J Clin Endocrinol Metab. 2005 Dec;90(12):6678-86 [PMID: 16204373]
  27. Diabetes Metab. 2002 Dec;28(6 Pt 1):448-56 [PMID: 12522324]
  28. J Mol Endocrinol. 2007 Feb;38(1-2):193-206 [PMID: 17293440]
  29. Diabetes. 1994 Feb;43(2):173-9 [PMID: 8288040]
  30. Diabetes. 2005 Apr;54(4):1150-6 [PMID: 15793255]
  31. Annu Rev Biochem. 2008;77:289-312 [PMID: 18518822]
  32. Am J Physiol. 1990 Sep;259(3 Pt 2):R612-7 [PMID: 2204282]
  33. Diabetologia. 2000 Sep;43(9):1165-9 [PMID: 11043863]
  34. J Biol Chem. 2002 Jan 18;277(3):1941-8 [PMID: 11707457]
  35. Diabetes. 2003 Mar;52(3):581-7 [PMID: 12606496]
  36. N Engl J Med. 2001 May 3;344(18):1343-50 [PMID: 11333990]
  37. Diabet Med. 2005 Aug;22(8):963-72 [PMID: 16026359]
  38. Cancer Ther. 2008;6(A):25-34 [PMID: 19079765]
  39. Diabetes. 2000 Dec;49(12):2094-101 [PMID: 11118012]
  40. J Clin Invest. 1987 Oct;80(4):1037-44 [PMID: 3308956]
  41. Expert Opin Investig Drugs. 2006 Sep;15(9):1039-49 [PMID: 16916271]
  42. Diabetes. 2002 Sep;51(9):2796-803 [PMID: 12196473]
  43. Diabetes. 1985 Mar;34(3):222-34 [PMID: 3882489]
  44. Nat Clin Pract Endocrinol Metab. 2008 Mar;4(3):156-63 [PMID: 18212765]
  45. J Biol Chem. 2008 Nov 21;283(47):32462-70 [PMID: 18718916]
  46. Diabetologia. 2004 Apr;47(4):597-613 [PMID: 15298336]
  47. Endocrinology. 1998 Jan;139(1):172-8 [PMID: 9421412]

MeSH Term

Diabetes Mellitus, Type 2
Humans
Insulin-Secreting Cells
PPAR gamma
Prediabetic State
Thiazolidinediones

Chemicals

PPAR gamma
Thiazolidinediones
Journal Article Review

Word Cloud

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