TRANSCRIPTIONAL INHIBITION OF INSULIN BY FK506 AND POSSIBLE INVOLVEMENT OF FK506 BINDING PROTEIN-12 IN PANCREATIC Β-Cell

TAMUKA, KOUCHIT; Fujimura, Takao; Tsutsumi, Takeshi; Nakamura, Keiko; Ogawa, Toshikazu; ATLIMARU, CHIZURU; Hirano, Yuri; Ohara, Kaname; Ohtsuka, Kazuyuki; Shimomura, Kyoichi; Kobayashi, Masakazu

doi:10.1097/00007890-199506150-00018

Cited by 19 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 The diabetogenic action of FK506 on pancreatic b cells is due to transcriptional inhibition of insulin. 10 No diabetogenic adverse effects were observed in the 12 patients treated with FK506 in this long term study, but it has been reported that diabetes mellitus exacerbated by FK506 can be relieved by dose reduction. 9 In summary, long term use of FK506 in low doses (2-4.5 mg/day) is safe and effective in patients with generalised MG in association with prednisolone reduction.…”

Section: Discussionmentioning

confidence: 61%

Long-term treatment of generalised myasthenia gravis with FK506 (tacrolimus)

Konishi

Yoshiyama²,

Takamori³

et al. 2005

Journal of Neurology, Neurosurgery & Psychiatry

View full text Add to dashboard Cite

Efficacy and safety of long term use of FK506 (2-4.5 mg/ day) for a maximum of two years were evaluated in 12 patients with generalised myasthenia gravis (MG). At the end of the study, eight patients (67%) showed improvement in either MG score or Activities in Daily Living score, and prednisolone dosage could be reduced in seven patients (58%), with a mean reduction ratio of 37%. Long term use of FK506 for MG can be more effective than short term administration, with no serious side effects.

show abstract

Section: Discussionmentioning

confidence: 61%

Long-term treatment of generalised myasthenia gravis with FK506 (tacrolimus)

Konishi

Yoshiyama²,

Takamori³

et al. 2005

Journal of Neurology, Neurosurgery & Psychiatry

View full text Add to dashboard Cite

show abstract

“…Several studies have demonstrated that tacroli-mus inhibits insulin secretion from the beta-cell [19,20,21,22,23]. Following a 2-week treatment course, tacrolimus reversibly suppressed insulin gene transcription in normal rats [23]. Furthermore, there are several reports suggesting that tacrolimus damages the beta-cell directly.…”

Section: Discussionmentioning

confidence: 99%

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis

Greenspan

Gitelman

Leung

et al. 2002

Pediatric Nephrology

View full text Add to dashboard Cite

There is limited information regarding the incidence and features of post-transplant diabetes mellitus (PTDM) in pediatric renal transplant recipients. We noted a recent increased frequency of PTDM and reviewed charts of children who underwent renal transplantation from 1 September 1986 to 31 August 1999 to characterize the risk factors and natural history of PTDM. Sixteen children were identified with PTDM, and were each matched with two transplanted controls who did not develop PTDM. Clinical presentation varied from asymptomatic hyperglycemia to hyperosmolar dehydration or diabetic ketoacidosis. The mean time from transplantation to PTDM presentation was 1.2 years (range 1 day to 6.2 years). Significant risk factors for PTDM included: first degree family history of type 2 DM [odds ratio (OR) 23.9]; second degree family history of type 2 DM (OR 5.8); tacrolimus use (OR 9.1 versus cyclosporin); and hyperglycemia in the 2 weeks immediately after transplantation (OR 4.7). Seven of eight children with persistent PTDM continue to receive insulin. Patients with persistent PTDM had later onset disease (mean 1.9 years) compared to those with transient PTDM (0.3 years), suggesting different pathophysiologic processes. We suggest that all children undergoing renal transplantation be screened routinely for PTDM after transplantation, and that such patients may benefit from the avoidance of tacrolimus, as it may cause permanent beta-cell injury.

show abstract

“…This calcium/calmodulin-dependent serine/threonine protein phosphatase is unique among the protein phosphatases and has been conserved from yeast to man. Calcineurin is widely distributed among tissues, including islet cells of the endocrine pancreas (19–21), skeletal muscle, heart, neurons, and adipocytes (22, 23). Calcineurin is a key enzyme in many cellular processes including antigen-stimulated T-lymphocyte activation, skeletal-muscle gene expression and remodeling, and the formation of the embryonic cardiovascular system (24).…”

Section: Structure and Function Of Calcineurinmentioning

confidence: 99%

Calcineurin Inhibition and New-Onset Diabetes Mellitus After Transplantation

Chakkera

Mandarino

2013

Transplantation

View full text Add to dashboard Cite

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 β-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.

show abstract

TRANSCRIPTIONAL INHIBITION OF INSULIN BY FK506 AND POSSIBLE INVOLVEMENT OF FK506 BINDING PROTEIN-12 IN PANCREATIC Β-Cell

Cited by 19 publications

References 0 publications

Long-term treatment of generalised myasthenia gravis with FK506 (tacrolimus)

Long-term treatment of generalised myasthenia gravis with FK506 (tacrolimus)

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis

Calcineurin Inhibition and New-Onset Diabetes Mellitus After Transplantation

Contact Info

Product

Resources

About