Calcineurin inhibition and new-onset diabetes mellitus after transplantation

Harini A. Chakkera, Lawrence J. Mandarino

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

New-onset diabetes after transplantation independently increases the risk of cardiovascular disease, infections, and graft loss and decreases patient survival. The required balance between insulin sensitivity/resistance and insulin secretion is necessary to maintain normal glucose metabolism. Calcineurin inhibitors are standard immunosuppression drugs used after transplantation and have been implicated in the development of new-onset diabetes after transplantation partially by pancreatic A-cell apoptosis and resultant decrease in insulin secretion. The ability of muscle to take up glucose is critical to blood glucose homeostasis. Skeletal muscle is quantitatively the most important tissue in the body for insulin-stimulated glucose disposal and is composed of diverse myofibers that vary in their properties between healthy and insulin-resistant muscle. Various signaling pathways are responsible for remodeling of skeletal muscle, and among these is the calcineurin/nuclear factor of activated T-cell pathway. The mechanism of action of the calcineurin inhibitors is to bind in a complex with a binding protein to calcineurin and inhibit its dephosphorylation and activation of nuclear factor of activated T cells. In this review, we will provide a detailed discussion of the hypothesis that inhibition of calcineurin in tissues involved in insulin sensitivity/resistance could be at least partially responsible for the diabetogenicity seen with the use of calcineurin inhibitors.

Original languageEnglish (US)
Pages (from-to)647-652
Number of pages6
JournalTransplantation
Volume95
Issue number5
DOIs
StatePublished - Mar 15 2013
Externally publishedYes

Fingerprint

Calcineurin
Insulin Resistance
Diabetes Mellitus
Transplantation
Insulin
NFATC Transcription Factors
Glucose
Skeletal Muscle
Cardiovascular Infections
Glucagon-Secreting Cells
Muscles
Immunosuppression
Blood Glucose
Carrier Proteins
Homeostasis
Cardiovascular Diseases
Apoptosis
Transplants
Survival
Pharmaceutical Preparations

Keywords

  • Glucose intolerance
  • Insulin resistance
  • Insulin secretion

ASJC Scopus subject areas

  • Transplantation

Cite this

Calcineurin inhibition and new-onset diabetes mellitus after transplantation. / Chakkera, Harini A.; Mandarino, Lawrence J.

In: Transplantation, Vol. 95, No. 5, 15.03.2013, p. 647-652.

Research output: Contribution to journalArticle

Chakkera, Harini A. ; Mandarino, Lawrence J. / Calcineurin inhibition and new-onset diabetes mellitus after transplantation. In: Transplantation. 2013 ; Vol. 95, No. 5. pp. 647-652.
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