New-Onset Posttransplantation Diabetes Mellitus: Insulin Resistance or Insulinopenia? Impact of Immunosuppressive Drugs, Cytomegalovirus and Hepatitis C Virus Infection

Hjelmesæth, Jøran; Åsberg, Anders; Müller, Fredrik; Hartmann, Anders; Jenssen, Trond

doi:10.2174/1573399052952604

Cited by 39 publications

(51 citation statements)

References 104 publications

(157 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8 It has long been known that CsA treatment is correlated with the onset of PTDM, for reasons that remain to be elucidated. 3,29,30 The differing effects of two ZnT-8 variants on GSIS suggest that patients undergoing CsA immunosuppressive treatment who have the 'low-risk' ZnT-8 variant (W325) may retain insulin-secreting capacity compared with those who have the 'high-risk' variant; this may account for the protective ZnT-8 polymorphism and cyclosporin A I Kim et al effect of the W325 allele with respect to PTDM. This also suggests that impairment of insulin secretion by CsA may contribute to PTDM.…”

Section: Discussionmentioning

confidence: 99%

A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion

et al. 2010

View full text Add to dashboard Cite

SLC30A8 encodes the b-cell-specific zinc transporter-8 (ZnT-8) expressed in insulin secretory granules. The single-nucleotide polymorphism rs13266634 of SLC30A8 is associated with susceptibility to post-transplantation diabetes mellitus (PTDM). We tested the hypothesis that the polymorphic residue at position 325 of ZnT-8 determines the susceptibility to cyclosporin A (CsA) suppression of insulin secretion. INS (insulinoma)-1E cells expressing the W325 variant showed enhanced glucose-stimulated insulin secretion (GSIS) and were less sensitive to CsA suppression of GSIS. A reduced number of insulin granule fusion events accompanied the decrease in insulin secretion in CsA-treated cells expressing ZnT-8 R325; however, ZnT-8 W325-expressing cells exhibited resistance to the dampening of insulin granule fusion by CsA, and transported zinc ions into secretory vesicles more efficiently. Both tacrolimus and rapamycin caused similar suppression of GSIS in cells expressing ZnT-8 R325. However, cells expressing ZnT-8 W325 were resistant to tacrolimus, but not to rapamycin. The Down's syndrome candidate region-1 (DSCR1), an endogenous calcineurin inhibitor, overexpression and subsequent calcineurin inhibition significantly reduced GSIS in cells expressing the R325 but not the W325 variant, suggesting that differing susceptibility to CsA may be due to different interactions with calcineurin. These data suggest that the ZnT-8 W325 variant is protective against CsA-induced suppression of insulin secretion. Tolerance of ZnT-8 W325 to calcineurin activity may account for its protective effect in PTDM.

show abstract

Section: Discussionmentioning

confidence: 99%

A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Insulin resistance and relative insulin deficiency are involved in the pathogenesis of both disorders [93]. The impact of insulin deficiency and insulin resistance may vary in the presence of different risk factors; among these, the type of immunosuppressant accounted for 74% of the variability in the 12-month cumulative incidence of NODAT [94].…”

Section: New-onset Diabetes Mellitus After Solid Organ Transplantationmentioning

confidence: 99%

“…The predominant underlying mechanism is increased insulin resistance based on OGTTtest (OGTT) [93]. In vivo and in vitro animal studies have demonstrated that GC interfere at several steps in the insulin signaling cascade in skeletal muscles, resulting in reduced glucose uptake and glycogen synthesis [98].…”

Section: Glucocorticoidsmentioning

confidence: 99%

See 1 more Smart Citation

Prevalence of Metabolic Syndrome in Organ Transplantation: A Review of the Literature

Pinna¹,

Pagotto²

2015

Endocrinol Metab Syndr

View full text Add to dashboard Cite

The clinical features of the Metabolic Syndrome (MS) as risk factors for transplantation have been cited separately and extensively in the transplant literature. There are few studies in literature evaluating the prevalence of MS before and after solid organ transplantation.MS puts transplant patients at risk in in two ways: 1) MS is one more risk factor to be considered in the pretransplantation workup; and 2) the combined risk of cardiovascular disease post-transplantation as a side effect of immunosuppressive medication together with the risk from cardiovascular disease stemming from the MS might put a post-transplantation patient at vastly increased risk for a cardiovascular event.There are several reports on the treatment of MS expecially after transplantation; from lifestyle changes to drug therapies. However, to now, guidelines about management of these patients are lacking.

show abstract

“…[100] Cytomegalovirus infection increases the activity of tumor necrosis factor(TNF), TNF can affect the function of islet B cell and decrease the organism's sensitivity to insulin, that will promote insulin resistance in renal transplant recipients.…”

Section: Virus Infectionmentioning

confidence: 99%

Metabolic Syndrome Associated Kidney Damage

Zou¹,

Wang²,

Zou³

et al. 2011

An Update on Glomerulopathies - Clinical and Treatment Aspects

View full text Add to dashboard Cite

New-Onset Posttransplantation Diabetes Mellitus: Insulin Resistance or Insulinopenia? Impact of Immunosuppressive Drugs, Cytomegalovirus and Hepatitis C Virus Infection

Cited by 39 publications

References 104 publications

A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion

A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion

Prevalence of Metabolic Syndrome in Organ Transplantation: A Review of the Literature

Metabolic Syndrome Associated Kidney Damage

Contact Info

Product

Resources

About