Effect of Cyclosporin a on Allotransplanted Pancreatic Fragments to the Spleen of Totally Pancreatectomized Dogs

Df, Du Toit; H, Reece-Smith; McShane, Paul; Denton, T. G.; Pj, Morris

doi:10.1097/00007890-198203000-00018

Cited by 27 publications

(17 citation statements)

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“…These findings are consistent with previous in vitro and in vivo studies of pancreatic β‐cell function in dogs following CsA treatment 18,25,26,32,42,43 . For example, a study of plasma glucose and insulin responses to intravenous glucagon in six healthy beagles before, during, and 1 and 4 months after the administration of CsA at a dosage of 20 mg/kg daily 25 reported that insulin secretion in response to glucagon was inhibited during the administration of CsA.…”

Section: Discussionsupporting

confidence: 90%

Ciclosporin A therapy is associated with disturbances in glucose metabolism in dogs with atopic dermatitis

Kovalik¹,

Thoday²,

Handel³

et al. 2010

Veterinary Dermatology

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The effect of ciclosporin A (CsA) on glucose homeostasis was investigated in 16 dogs with atopic dermatitis by determining plasma glucose, serum fructosamine and insulin concentrations, and serial insulin and glucose concentrations following a glucagon stimulation test, before and 6 weeks after CsA therapy at 5 mg/kg once daily. All dogs completed the study. Following CsA treatment, the median serum fructosamine concentrations were significantly higher (pretreatment 227.5 μmol/L; post-treatment 246.5 μmol/L; P = 0.001; reference range 162-310 μmol/L). Based on analyses of the areas under concentration-time curves (AUC) pre- and post-CsA treatment, plasma glucose concentrations were significantly higher (AUC without baseline correction 31.0 mmol/L/min greater; P = 0.021) and serum insulin concentrations were significantly lower (AUC without baseline correction 217.1 μIU/mL/min lower; P = 0.044) following CsA treatment. Peak glucose concentrations after glucagon stimulation test were significantly higher following CsA treatment (10.75 versus 12.05 mmol/L; P = 0.021), but there was no significant difference in peak serum insulin (52.0 versus 35.0 μIU/mL; P = 0.052). There was a negative correlation between baseline uncorrected insulin AUC and trough serum log CsA concentrations (r = -0.70, P = 0.005). The administration of CsA to dogs with atopic dermatitis leads to disturbances in glucose homeostasis. The clinical significance of this is unclear, but it should be taken into account when considering CsA treatment in dogs that already have such impairments.

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Section: Discussionsupporting

confidence: 90%

Ciclosporin A therapy is associated with disturbances in glucose metabolism in dogs with atopic dermatitis

Kovalik¹,

Thoday²,

Handel³

et al. 2010

Veterinary Dermatology

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“…Experimental diabetes can be corrected in the rat by transplantation of isolated islets into the liver via the portal vein or into the splenic parenchyma, and in the dog by implantation of dispersed pancreas into the spleen. Despite the delivery of insulin directly into the portal system in these models subsequent glucose tolerance tests are not strictly normal although the animals are essentially normoglycaemic [5][6][7][8][9][10][11]. This might be due to transplantation of inadequate numbers of islets or to damage to the islets during their preparation.…”

mentioning

confidence: 99%

Glucose and insulin changes following a renoportal shunt in streptozotocin diabetic rats with pancreatic islet isografts under the kidney capsule

McShane

Morris

1982

Diabetologia

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Summary. The effect on glucose metabolism of altering the site of the venous drainage of an isograft of isolated adult islets implanted beneath the renal capsule, from the systemic circulation to the portal circulation was determined in streptozotocininduced diabetic rats. Reversal of diabetes was accomplished by the transplantation of 1000-1200 isolated islets beneath the left kidney capsule. The rate of fall of the glucose concentration (as expressed by the K value) was found to be significantly decreased in transplanted animals (1.7 _+ 0.5%/rain; mean + SD) compared with normal animals (2.4 + 0.5%/rain). Draining the left renal vein into the portal circulation restored the K value to that of normal animals (2.5 + 0.4%). However the fasting glucose concentration was significantly higher and the basal insulin levels lower in both normal and transplanted rats with a renoportal shunt.

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“…Du Toit and colleagues performed intrasplenic allogeneic islet transplantation in pancreatomized dogs treated with cyclosporin and showed that survival was extended in comparison with non-immunosuppressed dogs [113]. Moreover, this allogeneic transplant dog model helped demonstrate the usefulness of rapamycin in transplantation [115].…”

Section: Characteristics Of the Spleen As An Islet Transplant Sitementioning

confidence: 99%

Spleen, as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem Cells

Sakata¹,

Yoshimatsu²,

Kodama³

2018

Preprint

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In this review, we show the unique potential of spleen as an optimal site for islet transplantation and a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy to treat severe diabetes mellitus, but its clinical outcome is unsatisfactory at present. One factor in clinical success of this therapy is selection of the most appropriate transplantation site. The spleen has been studied for a long time as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity. Recently it has also been shown that the spleen contributes to the regeneration of transplanted islets. The efficacy of transplantation is not as high as that obtained with intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established before the spleen can be effectively used in the clinic. Spleen also has an interesting aspect as a mesenchymal stem cell reservoir. The splenic mesenchymal stem cells contribute to tissue repair in damaged tissue, and thus, the infusion can be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.

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Effect of Cyclosporin a on Allotransplanted Pancreatic Fragments to the Spleen of Totally Pancreatectomized Dogs

Cited by 27 publications

References 0 publications

Ciclosporin A therapy is associated with disturbances in glucose metabolism in dogs with atopic dermatitis

Ciclosporin A therapy is associated with disturbances in glucose metabolism in dogs with atopic dermatitis

Glucose and insulin changes following a renoportal shunt in streptozotocin diabetic rats with pancreatic islet isografts under the kidney capsule

Spleen, as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem Cells

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