Increased β-Cell Replication and β-Cell Mass Regeneration in Syngeneically Transplanted Rat Islets Overexpressing Insulin-Like Growth Factor II

Abstract

Insulin-like growth factor II (IGF2) is a growth-promoting peptide that increases β-cell proliferation and survival. The aim of the study was to determine the effect of IGF2 overexpression on β-cell mass in transplanted islets. Islets infected with adenovirus encoding for IGF2 (Ad-IGF2 group), for luciferase (Ad-Luc control group), or with uninfected islets (control group) were syngeneically transplanted to streptozotocin-diabetic Lewis rats. Eight hundred islets, a minimal mass model to restore normoglycemia, or 500 islets, a clearly insufficient mass, were transplanted. Rats transplanted with 800 Ad-IGF2 islets showed a better metabolic evolution than control groups. As expected, rats transplanted with 500 Ad-IGF2 or control islets maintained similar hyperglycemia throughout the study, ensuring comparable metabolic conditions among both groups. β-Cell replication was higher in Ad-IGF2 group than in control group on days 3 Apoptosis was similarly increased in Ad-IGF2 and control islets after transplantation. No differences in insulin secretion were found between Ad-IGF2 and uninfected control islets. In summary, IGF2 overexpression in transplanted islets increased β-cell replication, induced the regeneration of the transplanted β-cell mass, and had a beneficial effect on the metabolic outcome reducing the β-cell mass needed to achieve normoglycemia.

Insulin-like growth factor 2 mitigates depressive behavior in a rat model of chronic stress

“…They can modulate the proliferation, survival, and differentiation of many types of neuronal systems, including cholinergic, dopaminergic, and serotonergic neurons (Estil et al, 2012;Silva et al, 2000). IGF2 À/À mice have developmental deficits, as evidenced by reduced brain volume (Constancia et al, 2002).…”

Human Serum versus Human Serum Albumin Supplementation in Human Islet Pretransplantation Culture: In Vitro and in Vivo Assessment

“…We speculate that the in vitro effects of HS on islet cell viability and function may not be sufficient by themselves to have a significant impact on transplanted islets when they face the difficult conditions of islet implantation and survival after transplantation (27). We and others have shown the difficulty of reducing β-cell death in the initial days after islet transplantation (10,11,32,43). Nevertheless, the positive in vitro results indicate that supplementation of culture medium with HS optimizes the number of islets available for transplantation, and it may be expected that it could have an additional beneficial impact if used in combination with other strategies to improve islet transplantation outcome.…”

A Model for Human Islet Transplantation to Immunodeficient Streptozotocin-Induced Diabetic Mice

“…Use of human islets was approved by the Ethics Committee of Hospital of Bellvitge, and written, signed consent was obtained from donor relatives. Mouse islets were isolated by collagenase (Collagenase P; Roche diagnostics, Mannheim, Germany) digestion of the pancreas 26 .…”

“…In experimental islet transplantation to rodents, STZ-diabetes must be induced before islet transplantation to avoid the concomitant destruction of grafted islets. Thus, STZ is first injected and once diabetes is confirmed several days later, islet transplantation is performed [24][25][26] . The availability of rodent islet donors is at the discretion of the investigator, and islet isolation and transplantation can be planned well in advance and conveniently performed once diabetes has been confirmed in the recipient.…”