Diabetes alters the response to bacteria by enhancing fibroblast apoptosis

Endocrinology. 2004 Jun;145(6):2997-3003. doi: 10.1210/en.2003-1601. Epub 2004 Mar 19.


Diabetics suffer from both more frequent bacterial infections and greater consequences of infection. However, bacteria-induced tissue destruction and the subsequent response in diabetics have received relatively little attention. To investigate this issue, we inoculated the scalp of control or db/db diabetic mice, with the pathogen Porphyromonas gingivalis, which causes connective tissue destruction in humans. Both bacteria-induced cytokine expression and tissue loss were similar in diabetic and control mice. However, there was a significantly higher rate of fibroblast-specific apoptosis in the diabetic group, which was measured as cells that were double positive for the terminal deoxynucleotidyltransferase-mediated deoxy-UTP nick end labeling assay and expression of vimentin. The higher rate of fibroblast apoptosis could be explained in the diabetic group by enhanced levels of activated caspase-3. Apoptosis was evident during the peak healing period and coincided with reduced numbers of fibroblasts, diminished collagen I and III expression, and significantly reduced formation of new connective tissue matrix in diabetic mice. Thus, diabetes may impair the healing response to bacteria-induced connective tissue loss by increasing the number of caspase-3-activated fibroblasts, leading to greater apoptosis and reduced numbers of fibroblastic cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Bacteroidaceae Infections / complications*
  • Bacteroidaceae Infections / pathology
  • Bacteroidaceae Infections / physiopathology*
  • Cell Count
  • Diabetes Complications*
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / physiopathology*
  • Extracellular Matrix / metabolism
  • Fibroblasts* / pathology
  • Inflammation / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Porphyromonas gingivalis*
  • Scalp / microbiology
  • Scalp / pathology
  • Soft Tissue Infections / pathology