1995XenotransplantationRequires access

Transplantation of porcine islets in nude mice: Implications for islet replacement therapy in humans

Gordon C. Weir, Alberto M. Davaili, Yoshiji Ogawa, Luisa Scaglia, Ying‐Jian Wu, Jennifer Hollister, Susan Bonner‐Weir

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Abstract

Abstract: Porcine islets obtained from adult donors were transplanted under the kidney capsule of streptozotocin diabetic nude mice. Over a period of 30 days or more, blood glucose levels fell to values lower than those of normal mice but comparable to those of normal pigs; this change in the mice was probably being driven by a lower set point for glucose‐induced insulin secretion of porcine islets. Oral and intraperitoneal glucose tolerance tests had lower glucose profiles than those carried out in control mice. The mass of beta cell tissue in the porcine islet graft that cured the diabetes was about 1 mg, close to the normal beta cell mass of a mouse pancreas. When graft‐bearing kidneys were perfused in situ, there was a marked increase of insulin secretion to challenges with glucose and arginine. These results suggest that porcine islets could be a good source of tissue for human islet replacement therapy. Some of the ramifications of this possibility are discussed.

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Abstract: Porcine islets obtained from adult donors were transplanted under the kidney capsule of streptozotocin diabetic nude mice. Over a period of 30 days or more, blood glucose levels fell to values lower than those of normal mice but comparable to those of normal pigs; this change in the mice was probably being driven by a lower set point for glucose‐induced insulin secretion of porcine islets. Oral and intraperitoneal glucose tolerance tests had lower glucose profiles than those carried out in control mice. The mass of beta cell tissue in the porcine islet graft that cured the diabetes was about 1 mg, close to the normal beta cell mass of a mouse pancreas. When graft‐bearing kidneys were perfused in situ, there was a marked increase of insulin secretion to challenges with glucose and arginine. These results suggest that porcine islets could be a good source of tissue for human islet replacement therapy. Some of the ramifications of this possibility are discussed.

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Available abstract

Abstract: Porcine islets obtained from adult donors were transplanted under the kidney capsule of streptozotocin diabetic nude mice. Over a period of 30 days or more, blood glucose levels fell to values lower than those of normal mice but comparable to those of normal pigs; this change in the mice was probably being driven by a lower set point for glucose‐induced insulin secretion of porcine islets. Oral and intraperitoneal glucose tolerance tests had lower glucose profiles than those carried out in control mice. The mass of beta cell tissue in the porcine islet graft that cured the diabetes was about 1 mg, close to the normal beta cell mass of a mouse pancreas. When graft‐bearing kidneys were perfused in situ, there was a marked increase of insulin secretion to challenges with glucose and arginine. These results suggest that porcine islets could be a good source of tissue for human islet replacement therapy. Some of the ramifications of this possibility are discussed.

Key concepts: Islet, Renal capsule, Transplantation, Endocrinology, Internal medicine, Insulin, Pancreas, Beta cell

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