Beta Cell Function After Islet Transplantation

Takita, Morihito; Seven, Nigar; Levy, Marlon F.; Naziruddin, Bashoo

doi:10.5772/52952

Cited by 1 publication

(1 citation statement)

References 131 publications

(96 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After decades of refinements in surgical procedures, 50% of patients who received allo-transplant remained insulin independent 5 years post-transplant with modern immunosuppression protocols 3 , and around 30% of patients who underwent total pancreatectomy with islet autotransplantation (TPIAT) remained insulin independent 2 years post-surgery 1 . Other than insulin dependency, clinical assessments such as Igls, β-score 4,5 , hypoglycemic occurrence, homeostasis model assessment (HOMA) 2-B%, secretory units of islets in transplantation 6 , have been proposed to evaluate graft function. However, whether these indicators can be used to predict transplant outcomes remains to be tested.…”

Section: Introductionmentioning

confidence: 99%

Elevated islet prohormone ratios as indicators of insulin dependency in islet transplant recipients

Chen¹,

Klimek‐Abercrombie²,

Potter³

et al. 2021

Preprint

View full text Add to dashboard Cite

Autologous pancreatic islet transplantation is an established therapy for patients with chronic pancreatitis. However, the long-term transplant outcomes are modest. Identifying indicators of graft function will aid the preservation of transplanted islets and glycemic control. To this end, we analyzed beta cell prohormone peptide levels in a retrospective cohort of total pancreatectomy autologous islet transplant patients (n=28). Proinsulin-to-C-peptide (PI/C) and proIAPP-to-total IAPP (proIAPP/IAPP) ratios measured at 3 months post-transplant were significantly higher in patients who remained insulin dependent at 1 year follow-up. In a mouse model of human islet transplantation, recipient mice that later became hyperglycemic displayed significantly higher PI/C ratios than mice that remained normoglycemic. Histological analysis of islet grafts showed reduced insulin- and proinsulin-positive area, but elevated glucagon-positive area in grafts that experienced greater secretory demand. Increased prohormone convertase 1/3 was detected in glucagon-positive cells, and glucagon-like peptide 1 (GLP-1) area was elevated in grafts from mice that displayed hyperglycemia or elevated plasma PI/C ratio, demonstrating intra-islet incretin production in metabolically challenged human islet grafts. These data indicate that in failing grafts, alpha cell prohormone processing is likely altered, and incomplete beta cell prohormone processing may be an early indicator of insulin dependency.

show abstract