Cyclosporin-induced inhibition of insulin secretion in isolated rat islets and HIT cells

Robertson, R. Paul

doi:10.2337/diabetes.35.9.1016

Cited by 39 publications

(22 citation statements)

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“…Controversy exists as to the potential for agents such as cyclosporine and tacrolimus to alter islet function in a clinical setting. Cyclosporine A has been reported to adversely affect insulin secretion and insulin gene transcription in islets and islet cell lines (15), although 2 years of treatment with cyclosporine A did not alter insulin secretion in patients with multiple sclerosis (16). Recently, we reported that tacrolimus has significant negative effects on insulin release and insulin gene transcription in the HIT-T15 ␤-cell line (17), and tacrolimus has been reported to be diabetogenic in patients receiving renal transplantation (18).…”

Section: A B C Dmentioning

confidence: 95%

Successful islet autotransplantation in humans: functional insulin secretory reserve as an estimate of surviving islet cell mass.

et al. 1998

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Islet autotransplantation for treatment of chronic painful pancreatitis in nondiabetic patients reliably establishes normoglycemia and phasic insulin secretion and can achieve prolonged insulin independence. Whether functional transplanted beta-cell reserve is normal after intrahepatic islet transplantation is not known, nor is it known whether conventional measures of insulin secretion accurately reflect the functional beta-cell mass. To determine insulin secretory reserve after islet transplant, we performed studies of glucose potentiation of arginine-induced insulin secretion (GPAIS) in eight recipients of intrahepatic islet autotransplants. All eight subjects (and matched, healthy controls) were studied cross-sectionally 49 +/- 12 months posttransplant, and four subjects were studied pre- and posttransplant. Subjects had received a mean +/- SE of 479,000 +/- 79,000 islets, and all were insulin independent and normoglycemic at the time of study. Acute insulin responses to arginine, glucose, and GPAIS were significantly reduced after islet transplantation in both study groups. Importantly, the magnitudes of these three responses were highly correlated to the mass of islets transplanted (response to glucose: r = 0.84, P < 0.01; response to arginine: r = 0.69, P < 0.05; response to GPAIS = 0.81, P < 0.01). Data from hemipancreatectomized and normal control subjects generally agreed with the regression lines. These findings demonstrate that despite normoglycemia and insulin independence, recipients of intrahepatic islet transplantation have significantly reduced functional beta-secretory reserve and that after islet transplantation, functional beta-cell mass can be estimated by measurements of glucose and arginine-induced insulin responses. Thus, these measurements can be used to estimate the mass and functional capacity of islets surviving intrahepatic transplantation in humans.

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Section: A B C Dmentioning

confidence: 95%

Successful islet autotransplantation in humans: functional insulin secretory reserve as an estimate of surviving islet cell mass.

et al. 1998

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“…In hindsight, perhaps the most important variable that distinguished the auto-and allotransplant settings and accounted for the inferior results was the differential requirement for systemic immunosuppression. Many of these agents, calcineurin inhibitors and corticosteroids in particular, are detrimental to islets [23,24]. Application of a new combination of maintenance agents, tacrolimus and sirolimus [25,26] without corticosteroids, combined with an interleukin-2 receptor antagonist induction agent and repeated infusions of purified islets, resulted in a dramatic breakthrough [27•].…”

Section: Results Of Human Clinical Trials Of Islet Transplantationmentioning

confidence: 99%

Clinical islet transplantation

Kaufman

Lowe

2003

Curr Diab Rep

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“…Several investigators have revealed that CsA, in therapeutically relevant doses, directly inhibits glucose-induced insulin release in isolated islets (Andersson et al, 1984;Nielson et al, 1986;Robertson, 1986;Draznin et al, 1988;Gillson et al, 1989;Gu, 1991;Shi et al, 1993;Dufer et al, 2001;Polastri et al, 2002;Yu et al, 2003). However, other in vitro studies showed no reduction in insulin secretion over a wide range of CsA concentrations (Laube and Hahn, 1985;Laube et al, 1986;Ebihara et al, 1996) or even increased insulin release following therapeutic dose of CsA (Ebihara et al, 1996).…”

Section: Discussionmentioning

confidence: 96%

Functional and morphological study of cultured pancreatic islets treated with cyclosporine

et al. 2007

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Cyclosporin-induced inhibition of insulin secretion in isolated rat islets and HIT cells

Cited by 39 publications

References 0 publications

Successful islet autotransplantation in humans: functional insulin secretory reserve as an estimate of surviving islet cell mass.

Successful islet autotransplantation in humans: functional insulin secretory reserve as an estimate of surviving islet cell mass.

Clinical islet transplantation

Functional and morphological study of cultured pancreatic islets treated with cyclosporine

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