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Brain death significantly reduces isolated pancreatic islet yields and functionality in vitro and in vivo after transplantation in rats.

Publication ,  Journal Article
Contreras, JL; Eckstein, C; Smyth, CA; Sellers, MT; Vilatoba, M; Bilbao, G; Rahemtulla, FG; Young, CJ; Thompson, JA; Chaudry, IH; Eckhoff, DE
Published in: Diabetes
December 2003

Although approximately 1 million islets exist in the adult human pancreas, current pancreas preservation and islet isolation techniques recover <50%. Presently, cadaveric donors remain the sole source of pancreatic tissue for transplantation. Brain death is characterized by activation of proinflammatory cytokines and organ injury during preservation and reperfusion. In this study, we assessed the effects of brain death on islet isolation yields and functionality. Brain death was induced in male 250- to 350-g Lewis rats by inflation of a Fogarty catheter placed intracranially. The rats were mechanically ventilated for 2, 4, and 6 h before removal of the pancreas (n = 6). In controls, the catheter was not inflated (n = 6). Shortly after brain death induction, a significant increase in serum tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 was demonstrated in a time-dependent manner. Upregulation of TNF-alpha, IL-1beta, and IL-6 mRNA was noted in the pancreas. Brain death donors presented lower insulin release after glucose stimulation assessed by in situ perfusion of the pancreas. Islet recovery was reduced in brain death donors compared with controls (at 6 h 602.3 +/- 233.4 vs. 1,792.5 +/- 325.4 islet equivalents, respectively; P < 0.05). Islet viability assessed in dissociated islet cells and in intact cultured islets was reduced in islets recovered from brain death donors, an effect associated with higher nuclear activities of NF-kappaB p50, c-Jun, and ATF-2. Islet functionality evaluated in vitro by static incubation and in vivo after intraportal transplantation in syngeneic streptozotocin-induced diabetic rats was significantly reduced in preparations obtained from brain death donors. In conclusion, brain death significantly reduced islet yields and functionality. These observations may lead to strategies to reduce the effects of brain death on pancreatic islets and improve the results in clinical transplantation.

Duke Scholars

Published In

Diabetes

DOI

ISSN

0012-1797

Publication Date

December 2003

Volume

52

Issue

12

Start / End Page

2935 / 2942

Location

United States

Related Subject Headings

  • Transcription Factors
  • Tissue Survival
  • Tissue Donors
  • Recovery of Function
  • Rats, Inbred Lew
  • Rats
  • Male
  • Islets of Langerhans Transplantation
  • Islets of Langerhans
  • Insulin Secretion
 

Citation

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Contreras, J. L., Eckstein, C., Smyth, C. A., Sellers, M. T., Vilatoba, M., Bilbao, G., … Eckhoff, D. E. (2003). Brain death significantly reduces isolated pancreatic islet yields and functionality in vitro and in vivo after transplantation in rats. Diabetes, 52(12), 2935–2942. https://doi.org/10.2337/diabetes.52.12.2935
Contreras, Juan L., Christopher Eckstein, Cheryl A. Smyth, Marty T. Sellers, Mario Vilatoba, Guadalupe Bilbao, Firoz G. Rahemtulla, et al. “Brain death significantly reduces isolated pancreatic islet yields and functionality in vitro and in vivo after transplantation in rats.Diabetes 52, no. 12 (December 2003): 2935–42. https://doi.org/10.2337/diabetes.52.12.2935.
Contreras JL, Eckstein C, Smyth CA, Sellers MT, Vilatoba M, Bilbao G, et al. Brain death significantly reduces isolated pancreatic islet yields and functionality in vitro and in vivo after transplantation in rats. Diabetes. 2003 Dec;52(12):2935–42.
Contreras, Juan L., et al. “Brain death significantly reduces isolated pancreatic islet yields and functionality in vitro and in vivo after transplantation in rats.Diabetes, vol. 52, no. 12, Dec. 2003, pp. 2935–42. Pubmed, doi:10.2337/diabetes.52.12.2935.
Contreras JL, Eckstein C, Smyth CA, Sellers MT, Vilatoba M, Bilbao G, Rahemtulla FG, Young CJ, Thompson JA, Chaudry IH, Eckhoff DE. Brain death significantly reduces isolated pancreatic islet yields and functionality in vitro and in vivo after transplantation in rats. Diabetes. 2003 Dec;52(12):2935–2942.

Published In

Diabetes

DOI

ISSN

0012-1797

Publication Date

December 2003

Volume

52

Issue

12

Start / End Page

2935 / 2942

Location

United States

Related Subject Headings

  • Transcription Factors
  • Tissue Survival
  • Tissue Donors
  • Recovery of Function
  • Rats, Inbred Lew
  • Rats
  • Male
  • Islets of Langerhans Transplantation
  • Islets of Langerhans
  • Insulin Secretion