Effects of cyclosporin treatment on prolactin pulsatility in chronic hyperprolactinemic male rats

Lafuente, A.; Salgado, Aurora; Garcı́a-Bonacho, Manuel; Esquifino, Ana I.

doi:10.1016/0165-5728(95)00179-4

Cited by 9 publications

(6 citation statements)

References 22 publications

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“…The impairment of insulin sensitivity seen in this study could not be explained by regulation of the counter‐regulatory hormone glucagon or changes in circulating free fatty acid levels. Reports of calcineurin inhibitor‐related effects on endocrine hormones are so far sparse, mainly suggesting limited impact of the drugs .…”

Section: Discussionsupporting

confidence: 54%

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The impact of calcineurin inhibitors on insulin sensitivity and insulin secretion: a randomized crossover trial in uraemic patients

et al. 2012

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Aims The calcineurin inhibitors cyclosporine and tacrolimus are implicated in post-transplant complications such as new-onset diabetes after transplantation. The relative contribution of each calcineurin inhibitor to new-onset diabetes after transplantation remains unclear. We sought to compare the impact of cyclosporine and tacrolimus on glucose metabolism in humans.Methods Eight haemodialysis patients received 8-10 days of oral treatment followed by 5-h infusions with cyclosporine, tacrolimus and saline in a randomized, investigator-blind, crossover study. Glucose metabolism and b-cell function was investigated through: a hyperinsulinaemic-euglycaemic clamp, an intravenous glucose tolerance test and insulin concentration time series.Results Cyclosporine and tacrolimus decreased insulin sensitivity by 22% (P = 0.02) and 13% (P = 0.048), respectively. The acute insulin response and pulsatile insulin secretion were not significantly affected by the drugs. ConclusionIn conclusion, 8-10 days of treatment with cyclosporine and tacrolimus impairs insulin sensitivity to a similar degree in haemodialysis patients, while acute insulin responses and pulsatile insulin secretion remain unaffected.Diabet. Med. 29, e440-e444 (2012)

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Section: Discussionsupporting

confidence: 54%

“…Diabetic Medicine ª 2012 Diabetes UK acid levels. Reports of calcineurin inhibitor-related effects on endocrine hormones are so far sparse, mainly suggesting limited impact of the drugs [23,24].…”

Section: Discussionmentioning

confidence: 99%

The impact of calcineurin inhibitors on insulin sensitivity and insulin secretion: a randomized crossover trial in uraemic patients

et al. 2012

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“…Although these hormones were not measured in this study, their actions would likely lead to deviations and differences in circulating glucose and FFA concentrations, which were not observed in this study. More importantly reports on CNI related effects on these neuroendocrine hormones are sparse and contradictory, mainly suggesting no or limited impact of the drugs [42–44].…”

Section: Discussionmentioning

confidence: 99%

Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers

Øzbay

Møller

Juhl

et al. 2012

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• New onset diabetes after transplantation is related to treatment with immunosuppressive medications. Clinical studies have shown that risk of new onset diabetes is greater with tacrolimus compared with ciclosporin. The diabetogenicity of ciclosporin and tacrolimus has been attributed to both beta cell dysfunction and impaired insulin sensitivity. WHAT THIS STUDY ADDS• This is the first trial to investigate beta cell function and insulin sensitivity using gold standard methodology in healthy human volunteers treated with clinically relevant doses of ciclosporin and tacrolimus. We document that both drugs acutely increase insulin sensitivity, while first phase and pulsatile insulin secretion remain unaffected. This study demonstrates that ciclosporin and tacrolimus have similar acute effects on glucose metabolism in healthy humans. AIMThe introduction of calcineurin inhibitors (CNIs) ciclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) cause impairment of survival rates. The relative contribution of each CNI to the pathogenesis and development of NODAT remains unclear. We sought to compare the impact of CsA and Tac on glucose metabolism in human subjects. METHODSTen healthy men underwent 5 h infusions of CsA, Tac and saline in a randomized, double-blind, crossover study. During infusion glucose metabolism was investigated using following methods: a hyperinsulinaemic-euglycemic clamp, an intravenous glucose tolerance test (i.v.GTT), glucose-stimulated insulin concentration-time series and indirect calorimetry. RESULTSClamp derived insulin sensitivity was increased by 25% during CsA (P < 0.0001) and 13% during Tac administration (P = 0.047), whereas first phase and pulsatile insulin secretion were unaffected. Coinciding with the CNI induced improved insulin sensitivity, glucose oxidation rates increased, while insulin clearance rates decreased, only non-significantly. Tac singularly lowered hsCRP concentrations, otherwise no changes were observed in circulating glucagon, FFA or adiponectin concentrations. Mean blood concentrations of CNIs were 486.9 Ϯ 23.5 mg l -1 for CsA and 12.8 Ϯ 0.5 mg l -1 for Tac. CONCLUSIONSAcute effects of i.v. CsA, and to a lesser degree Tac infusions, in healthy volunteers include increased insulin sensitivity, without any effect on first phase or pulsatile insulin secretion.

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“…The CsA blocks the prolactin (PRL) receptors in T and B lymphocytes, thus inhibiting the action of PRL. Consequently, there is an increase in PRL blood levels, suggesting influence in the steroidogenic function of the ovary and thus affecting the physiological state of the mammary gland 5,10,11 …”

Section: Discussionmentioning

confidence: 99%

“…Consequently, there is an increase in PRL blood levels, suggesting influence in the steroidogenic function of the ovary and thus affecting the physiological state of the mammary gland. 5,10,11 Regression of FAs is possible after discontinuation of CsA, 12 or switching to alternative agents, such as tacrolimus (FK) or mycophenolate. [13][14][15] Although both CsA and FK are calcineurim inhibitors and have similar characteristics, the adverse effects and calcineurim phosphatase inhibitory profiles are different.…”

Section: Discussionmentioning

confidence: 99%

First report of a fibro‐adenoma in axillary mammary tissue of a renal transplant patient taking cyclosporin

et al. 2007

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Effects of cyclosporin treatment on prolactin pulsatility in chronic hyperprolactinemic male rats

Cited by 9 publications

References 22 publications

The impact of calcineurin inhibitors on insulin sensitivity and insulin secretion: a randomized crossover trial in uraemic patients

The impact of calcineurin inhibitors on insulin sensitivity and insulin secretion: a randomized crossover trial in uraemic patients

Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers

First report of a fibro‐adenoma in axillary mammary tissue of a renal transplant patient taking cyclosporin

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