Islet transplantation and insulin administration relieve long-term complications and rescue the residual endogenous pancreatic β cells

Marina Figliuzzi, Roberto Bianchi, Cristina Cavagnini, Raffaella Lombardi, Carla Porretta-Serapiglia, Giuseppe Lauria, Federica Avezza, Annalisa Canta, Valentina Carozzi, Alessia Chiorazzi, Paola Marmiroli, Cristina Meregalli, Norberto Oggioni, Barbara Sala, Guido Cavaletti, Andrea Remuzzi

Research output: Contribution to journalArticlepeer-review

Abstract

Islet transplantation is a poorly investigated long-term strategy for insulin replacement and for treatment of complications in patients with diabetes. We investigated whether islet transplantation and insulin treatment can relieve diabetic neuropathy and rescue the residual endogenous pancreatic β cells. We used a multimodal approach, with five groups of Sprague-Dawley rats studied for 8 months: control rats, diabetic rats, insulin-treated diabetic rats with moderate or mild hyperglycemia, and diabetic rats transplanted with microencapsulated islets. Islet transplantation normalized glycemia and increased body and muscle weight; it was also effective in reducing proteinuria and altered liver function. Transplantation significantly improved tail nerve conduction velocity, Na+-K+-ATPase activity, and morphological alterations in the sciatic nerve as evidenced by decrease in g-ratio; it also restored thermal and ameliorated mechanical nociceptive thresholds. Morphometric analysis of pancreas indicated a significant β-cell volume increase in transplanted rats, compared with mildly and moderately hyperglycemic rats. Thus, allogeneic islet transplantation had a positive systemic effect in diabetic rats and induced regression of the established neuropathy and restitution of the typical characteristics of the islets. These findings strongly reinforce the need for improving glycemic control, not only to reverse established diabetic complications but also to improve β-cell status in diabetic pancreas.

Original languageEnglish
Pages (from-to)1527-1538
Number of pages12
JournalAmerican Journal of Pathology
Volume183
Issue number5
DOIs
Publication statusPublished - Nov 2013

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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