Immunological and insulin secretory studies on isolated porcine islets of Langerhans

Crowther, Nigel J.; Gotfredsen, Carsten F.; Moody, A. J.; Green, I. C.

doi:10.1677/joe.0.1260043

Cited by 31 publications

(10 citation statements)

References 21 publications

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“…Despite these encouraging results, the in vitro physiology of porcine islets has not yet been examined in detail. Their in vitro insulin release after an acute glucose stimulus is weak (Marchetti et al 1989, Crowther et al 1990) when compared with the insuhn release from rat or human islets (Giannarelli et al 1993, Hegre et al 1993, Takei et al 1994 or to the insulin release induced in pig islets by glucose plus IBMX, a phosphodiesterase inhibitor (Heald et al 1992). In this study, porcine islets cultured overnight showed no insulin response to glucose, as already reported (Davalli et al 1993), and the insulin response was still low after 48-h culture in CMRL 1066.…”

Section: Discussionmentioning

confidence: 99%

“…However, isolated pig islets cultured in standard media show an extremely poor response to glucose; moreover, immunohistochem¬ istry data (Davalli et al 1993) and total islet glucagon content (Crowther et al 1989) in the whole pancreas and in the isolated islets have shown that peripheral -cells are usually lost during the isolation procedures employed for porcine islets. It is possible to speculate that the loss of -cells, induced by isolation, might be one of the reasons for these secretory abnormalities (Crowther et al 1990). In fact, -cells seem to be crucial in maintaining adequate cychc adenosine monophosphate (cAMP) levels within B-cells, required for a normal insuhn response to glucose (Schuit & Pipeleers 1985).…”

Section: Introductionmentioning

confidence: 99%

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Glucagon improves insulin secretion from pig islets in vitro

Bertuzzi¹,

Berra

Socci

et al. 1995

Journal of Endocrinology

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It has been shown that peripheral glucagon secreting cells (A-cells) are lost during most of the isolation procedures employed for pig islets. Loss of A-cells decreases intra-islet glucagon levels and cAMP levels in B-cells and might reduce glucose-induced insulin release. This study was designed to test this hypothesis, by evaluating the effects of culture of porcine islets with exogenous glucagon on insulin secretion and on insulin and cAMP content in islets. Islets were isolated from adult 2-year old Large White pigs using an automated method. The number of A-cells was calculated by immunostaining for glucagon in islets before and after isolation and a significant decrease in A-cells was observed. After an overnight culture, islets were cultured for 48 h in a standard medium (CMRL 1066, 10% foetal calf serum, 1% antibiotics, 1% glutamine) alone or in the presence of glucagon at two different concentrations (1.0 and 10.0 microM); exposure to glucagon was either continuous or alternated with periods of incubation in CMRL 1066 alone. After the 48-h culture in standard medium, the islet glucagon response to arginine was almost negligible and significantly lower than that observed in human islets.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glucagon improves insulin secretion from pig islets in vitro

Bertuzzi¹,

Berra

Socci

et al. 1995

Journal of Endocrinology

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“…In this regard, pigs would be suitable donors, since they have a digestive physiology, glucose homeostasis, and regulation of insulin secretion similar to that of humans. [89][90][91] Furthermore, the amino acid sequence of porcine insulin differs from human insulin by only one amino acid. 92 A major barrier to xeno-islet transplantation is hyperacute rejection, mediated by natural antibodies and cellular immunity.…”

Section: Alternative Sources Of Insulin-producing Tissuementioning

confidence: 99%

Islet transplantation: present and future perspectives

Kenyon

Ranuncoli

Masetti

et al. 1998

Diabetes Metab. Rev.

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Islet cell transplantation can potentially normalize blood glucose levels and stop the progression of clinical complications, and if the transplant is done early in the course of the disease complications may be prevented. Remarkable progress has been made in recent years and islet cell transplantation has resulted in normalization of metabolic control in several patients with Type 1 diabetes in the absence of hypoglycemia. Only a few patients, however, have achieved insulin independence. Issues relating to islet cell engraftment within the liver, prevention of rejection and recurrent autoimmunity, and identification of alternative immunosuppressive drugs that do not adversely affect islet cell function remain to be solved. Thus far, the need for chronic, generalized immunosuppression to prevent rejection of the islets has limited the indication to those patients who have already received another transplant or to those who simultaneously receive islets and another organ (generally a kidney). Identification of immunointervention protocols that allow for engraftment in the absence of deleterious effects on the islets and prevent rejection and recurrent autoimmunity would make this procedure suitable for all patients, including children who have not yet developed long-term complications of the disease.

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“…features with humans, including a structural similarity between porcine and human insulin (7). Transplantation…”

Section: Introductionmentioning

confidence: 99%

AN69 Hollow Fiber Membrane will Reduce but Not Abolish the Risk of Transmission of Porcine Endogenous Retroviruses

Pakhomov¹,

Martignat

Honiger

et al. 2005

Cell Transplant

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As the risk of porcine endogenous retrovirus (PERV) infection is a major obstacle to the xenotransplantation of porcine tissue, we investigated whether an AN69 hollow fibre membrane, used for islets of Langerhans transplantation, could prevent the transfer of PERVs and thus reduce the risk of PERV infection. PK15 cells were used as a PERV source. A specific and highly sensitive RCR was used for detection of a PERV provirus DNA (gag region) and a porcine mtDNA. Human U293 cells were incubated in vitro with encapsulated PK15 cells, concentrated encapsulated PK15 supernatant, or concentrated PK15 supernatant as a control. CD1 mice were implanted in vivo with encapsulated PK15 cells or injected with PK15 supernatant. We found no infection in human cells incubated with either encapsulated PK15 supernatant or in 10 out of 11 samples after coincubation with encapsulated PK15 cells. Infection of human cells was, however, detected in 1 out of 11 samples after coincubation with encapsulated PK15 cells. The presence of PERV provirus DNA and porcine mtDNA was detected in all the investigated tissues of the mice injected with PK15 supernatant and in various tissues of the mice implanted with encapsulated PK15 cells. Four weeks after the last injection of PK15 supernatant or a fiber explantation, no mouse showed any presence of PERV provirus DNA or porcine mtDNA. Our results demonstrate that AN69 hollow fiber membrane will reduce but not abolish the risk of PERV infection. Because the real risk of PERV infection still remains unknown, it is necessary to investigate further the real protection that could be provided by hollow fibers to ensure the safety of clinical xenotransplantation.

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Immunological and insulin secretory studies on isolated porcine islets of Langerhans

Cited by 31 publications

References 21 publications

Glucagon improves insulin secretion from pig islets in vitro

Glucagon improves insulin secretion from pig islets in vitro

Islet transplantation: present and future perspectives

AN69 Hollow Fiber Membrane will Reduce but Not Abolish the Risk of Transmission of Porcine Endogenous Retroviruses

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