Evidence of increased islet cell proliferation in patients with recent-onset type 1 diabetes

Abstract

Aims/hypothesis In adults, the rate of beta cell replication is normally very low, but recent evidence suggests that it may increase during insulitis. We therefore studied tissue from donors with recent-onset type 1 diabetes to establish whether islet cell proliferation is increased during the disease process. Methods Paraffin-embedded pancreatic sections from ten donors with recent-onset type 1 diabetes and a range of relevant controls were stained by immunohistochemical techniques with antibodies against the proliferation markers Ki67 and minichromosome maintenance protein-2 (MCM-2). A combination staining technique involving immunoperoxidase and immunofluorescence methods was developed to quantify the numbers of alpha and beta cells with Ki67-positive nuclei and to investigate the relationship between insulitis and islet cell proliferation.

Sirtuin 3 regulates mouse pancreatic beta cell function and is suppressed in pancreatic islets isolated from human type 2 diabetic patients

“…A detection system (REAL Envision; Dako, Cambridge, UK) was used for antigen detection. For details of human donors [27][28][29], see ESM Methods and ESM Table 2.…”

Mini-Chromosome Maintenance Protein Family: Novel Proliferative Markers - The Pathophysiologic Role and Clinical Application

“…Willcox and coworkers (45) demonstrated that in type I diabetes Alpha and Beta cells undergo an increase in proliferation during progression. These cells show a high level of coexpression of Ki67 and MCM which are indicative of a proliferative response in an autoimmune attack during the course of diabetes type I. Qian and colleagues (44) showed that MCM complex can be effective in understanding the pathogenesis of many viral diseases.…”

Perspectives of Cell Therapy in Type 1 Diabetes

“…The  cell deficit in type 1 diabetes is related to the established autoimmune destruction of the target cells. However, several lines of research indicate that some  cell regeneration may occur in recent onset type 1 diabetic patients (Willcox et al, 2010) and even in patients with long-standing type 1 diabetes (Meier et al, 2005). The failure of  cell regeneration in type 1 diabetes may be related to the increased vulnerability of the newly forming  cells to apoptosis induced by inflammatory cytokines (Meier et al, 2006).…”