Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreas transplantation is considered the optimal therapy for patients with diabetes mellitus who reach end-stage renal disease. Despite achievement of euglycaemia after this procedure, the progression to impaired pancreatic function and metabolic exhaustion still represents one of the major concerns that increase the risk of graft loss. This paper reviews the possible mechanisms that can induce post-transplant hyperglycaemia, including those related to immunosuppression and those non-related, and the new strategies available for minimising or preventing this complication. Different aetiologies can induce pancreatic dysfunction. Technical complications, acute pancreatitis and delayed graft function, mostly related to impaired insulin secretion, are considered the early causes for abnormal glucose control. In general, acute rejection does not affect the endocrine portion of the pancreas graft because islet destruction occurs later than the inflammation of the exocrine components. Hyperinsulinaemia and insulin resistance represent the main concern for the progression of blood glucose intolerance. The anastomotic techniques of the exocrine portion of the pancreas and the immunosuppressive regimens are of critical importance for the development of impaired glucose metabolism. Hyperinsulinaemia, as a result of the fact that systemic-enteric or systemic-bladder drainages reducing the hepatic clearance of insulin, has led to the introduction of more physiological techniques using portal drainage of the endocrine secretions. Experimental and clinical data have shown that many of the current immunosuppressants account, to a large degree, for the increased risk of the development of post-transplant hyperglycaemia. The most common maintenance regimen in pancreatic transplantation still consists of triple therapy with a combination of corticosteroids, calcineurin inhibitors (either ciclosporin [cyclosporine] or tacrolimus), and mycophenolate mofetil (MMF).The diabetogenic effects of corticosteroids and calcineurin inhibitors have resulted in the need for protocols able to minimise their use. Recent studies have shown the safety and efficacy of steroid-sparing or -free regimens. Sirolimus has shown powerful immunosuppressive potency in absence of nephrotoxicity and diabetogenicity. Multicentre and single-centre reports have demonstrated that both calcineurin inhibitor withdrawal and avoidance were possible when sirolimus was used in a concentration-controlled fashion, with low-dose corticosteroids and MMF. Although the experience with sirolimus in pancreatic transplantation is still limited, the results are promising. Patients affected by diabetic gastroparesis seem to better tolerate a regimen with sirolimus and low-dose tacrolimus than one with tacrolimus in combination with MMF.For successful, long-term results of pancreatic transplantation, it is crucial to combine donor selection, technical aspects, modified anastomotic techniques and new therapeutic approaches designed to minimise the metabolic and non-metabolic adverse effects of the immunosuppressive regimens.
 ...
PMID:Management of hyperglycaemia after pancreas transplantation: are new immunosuppressants the answer? 1563 39

The rate of mycophenolic acid (MPA) absorption after oral administration of mycophenolate mofetil (MMF) is delayed in patients with diabetes. Cyclosporine (CsA) decreases MPA exposure by inhibiting enterohepatic recirculation of MPA/MPA glucuronide, and tacrolimus (TRL) may alter the rate and extent of MPA absorption due to its prokinetic properties especially in patients with diabetic gastroparesis. This study evaluated the effect of changing from CsA to TRL on pharmacokinetics of MPA in stable renal transplant recipients with long-standing diabetes. Eight patients were switched from a stable dose of CsA to TRL while taking MMF 1 g twice daily. The 12-hour steady-state total plasma concentration-time profiles of MPA and MPA glucuronide were obtained after oral administration of MMF on 2 occasions: first while taking CsA and second after changing to TRL. Pharmacokinetic parameters of MPA were calculated by the noncompartmental method. Changing from CsA to TRL resulted in significantly increased MPA exposure (area under the concentration-time curve from 0 to 12 hours, AUC0-12) by 46 +/- 32% (P = 0.012) and MPA predose concentration (C0) by 121 +/- 67% (P = 0.008). The magnitude of change in MPA exposure did not correlate well with MPA-C0 or CsA trough concentration. Switching to TRL had minimal impact on peak concentration of MPA (15.0 +/- 6.9 mg/L with CsA versus 16.1 +/- 9.7 mg/L with TRL, P = 0.773) and time to reach the peak concentration (1.0 +/- 0.4 hours with CsA versus 1.2 +/- 0.8 hours with TRL, P = 0.461). Highly variable and unpredictable changes in MPA exposure among renal transplant patients with diabetes do not support a strategy of preemptively adjusting MMF dose when switching calcineurin inhibitors in this population.
 ...
PMID:Impact of changing from cyclosporine to tacrolimus on pharmacokinetics of mycophenolic acid in renal transplant recipients with diabetes. 1870 92