Neither amyloid depositions nor hepatic steatosis are associated with marginal islet mass early after autotransplantation

Abstract

In 2008, Westermark et al. postulated that amyloid depositions found in allotransplanted islets derived from either islet overstimulation due to insulin production (as in type 2 diabetes), toxicity of immunosuppression, or perhaps both. 1 Amyloid depositions may promote a gradual decline in islet mass, progressive dysfunction, and ultimate

What Is New with Total Pancreatectomy and Autologous Islet Cell Transplantation? Review of Current Progress in the Field

“…Progressing islet amyloidosis after intraportal infusion has been suggested responsible for islet cell decline after transplant. However, this theory has been challenged recently based on clinical observations and pathological findings [ 40 , 41 ]. Insulin release stimulation assays allow accurate evaluation and monitoring of islet graft function following transplant, but these tests are logistically challenging given the often far proximity of patients to transplant centers and less reliable individual fasting values.…”

Lessons from Human Islet Transplantation Inform Stem Cell-Based Approaches in the Treatment of Diabetes

“…Immunosuppressive drugs necessary for islet allotransplant also carry risk for beta cell toxicity ( 21 ). Although intraportally transplanted islets are rarely accessible for study, limited histopathology of intraportal islet allografts have shown amyloid deposition, postulated due to over-stimulation of insulin production from a marginal islet mass or immunosuppressive drug toxicity ( 22 ); a recent report documenting absence of islet amyloid in an islet autograft patient with marginal islet mass suggests drug toxicity as a more likely culprit ( 23 ). More recently de-differentiation of the mature beta cell phenotype was observed in two islet allotransplant recipients, possibly consequences of hypoxia and metabolic stress ( 23 ).…”

“…Although intraportally transplanted islets are rarely accessible for study, limited histopathology of intraportal islet allografts have shown amyloid deposition, postulated due to over-stimulation of insulin production from a marginal islet mass or immunosuppressive drug toxicity ( 22 ); a recent report documenting absence of islet amyloid in an islet autograft patient with marginal islet mass suggests drug toxicity as a more likely culprit ( 23 ). More recently de-differentiation of the mature beta cell phenotype was observed in two islet allotransplant recipients, possibly consequences of hypoxia and metabolic stress ( 23 ). Innate immune destruction of islets stimulated upon intraportal infusion of islets has led to study of alternate sites for transplant, including omentum, bone marrow, intramuscular, and subcutaneous sites, though none has yet established the same efficacy as the liver ( 24 – 27 ).…”