Transplantation of pancreatic islets to adrenal gland is promoted by agonists of growth-hormone-releasing hormone

Undine Schubert, Janine Schmid, Susann Lehmann, Xian Y. Zhang, Henning Morawietz, Norman L. Block, Waldemar Kanczkowski, Andrew V. Schally, Stefan R. Bornstein, Barbara Ludwig

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Here, we evaluate an alternative approach of preconditioning pancreatic islets before transplantation using a potent agonist of growth-hormone-releasing hormone (GHRH) to promote islet viability and function, and we explore the adrenal gland as an alternative transplantation site for islet engraftment. The endocrine microenvironment of the adrenal represents a promising nichewith the unique advantages of exceptional high oxygen tension and local antiinflammatory and immunosuppressive properties. GHRH agonists have been shown to promote islet graft survival and function, which may help to reduce the islet mass necessary to reverse diabetes. In the present study, themost potent GHRH agonist MR403 was tested on insulinoma cells, isolated rat islets, and adrenal β-cell cocultures in vitro. GHRH receptor is expressed on both adrenal cells and islets. MR403 caused a significant increase in cell viability and proliferation and revealed an antiapoptotic effect on insulinoma cells. Viability of rat islets was increased after treatment with the agonist and in coculture with adrenal cells. Rat islets were transplanted into diabetic mice to the intraadrenal transplant site and compared with the classical transplants underneath the kidney capsule. Graft function and integration were tested by metabolic follow-up and immunohistochemical staining of intraadrenal grafts. A rapid decrease occurred in blood glucose levels in both models, and all animals reached normoglycemiawithin the first days after transplantation. Our studies demonstrated that the adrenal may be an attractive site for islet transplantation and that GHRH analogs might allow reduction of the islet mass needed to reverse a diabetic status.

Original languageEnglish (US)
Pages (from-to)2288-2293
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number6
DOIs
StatePublished - Feb 5 2013

Keywords

  • β-Cell replacement
  • Regenerative therapy
  • Type 1 diabetes mellitus

ASJC Scopus subject areas

  • General

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