Beta-cell expansion for therapeutic compensation of insulin resistance in type 2 diabetes.

Shimon Efrat

doi:10.1080/15438600303731

Abstract

Insulin resistance is the primary cause of type 2 diabetes. However, if compensated by increased insulin production, insulin resistance by itself does not lead to overt disease. Type 2 diabetes develops when this compensation is insufficient, due to defects in β-cell function and in regulation of the β-cell mass. β-Cell transplantation, as well as approaches that replenish or preserve the endogenous β-cell mass, may facilitate the treatment of type 2 diabetes in patients requiring exogenous insulin.

Highlights

The emerging understanding of embryonic β-cell development [6], and of β-cell regeneration in the adult pancreas from pancreatic ducts [7], may hold the promise of developing approaches to stimulate endogenous β-cell replenishment by neogenesis or replication
Beyond technical feasibility, is the functional performance of endogenous versus transplanted cells. It is not known whether the functional abnormalities observed in β cells in type 2 diabetes, as well as the increased rate of apoptosis, are caused by genetic defects or by epigenetic factors, such as the chronic hyperglycemia and deposits of islet amyloid polypeptide (IAPP), which characterize the β-cell milieu in type 2 diabetes
If epigenetic conditions are the main cause of β-cell failure in type 2 diabetes, autologous and allogeneic new β cells will be susceptible to a gradual deterioration in their function and viability

Summary

Introduction

The emerging understanding of embryonic β-cell development [6], and of β-cell regeneration in the adult pancreas from pancreatic ducts [7], may hold the promise of developing approaches to stimulate endogenous β-cell replenishment by neogenesis or replication. These approaches are likely to involve the local delivery of growth factors or other extracellular mitogenic agents, as well as the transfer of genes into pancreatic duct or islet cells that can modulate their replication and differentiation, or increase their resistance to apoptosis.

Results

Conclusion