β-Cell Deficit in Obese Type 2 Diabetes, a Minor Role of β-Cell Dedifferentiation and Degranulation

Abstract

Therefore, although we concur that in type 2 diabetes there are endocrine cells with altered cell identity, this process does not account for the deficit in β-cells in type 2 diabetes but may reflect, in part, attempted β-cell regeneration.

Chronic fractalkine administration improves glucose tolerance and pancreatic endocrine function

“…While increased β cell apoptosis may be responsible for the majority of decreased β cell mass in advanced T2DM patients (42,43), recently it has been suggested that an additional mechanism may exist. Thus, accumulation of dedifferentiated/ immature β cells, which express markers of both α and β cells, has been reported in mouse models of diabetes as well as in human T2DM islets (4,32,(43)(44)(45).…”

“…While increased β cell apoptosis may be responsible for the majority of decreased β cell mass in advanced T2DM patients (42,43), recently it has been suggested that an additional mechanism may exist. Thus, accumulation of dedifferentiated/ immature β cells, which express markers of both α and β cells, has been reported in mouse models of diabetes as well as in human T2DM islets (4,32,(43)(44)(45). While the origin of these dedifferentiated/immature β cells is still controversial in humans (32,43), it is plausible that strategies to suppress β cell apoptosis and/or increase β cell differentiation/maturation would be effective at improving β cell function.…”

“…Thus, accumulation of dedifferentiated/ immature β cells, which express markers of both α and β cells, has been reported in mouse models of diabetes as well as in human T2DM islets (4,32,(43)(44)(45). While the origin of these dedifferentiated/immature β cells is still controversial in humans (32,43), it is plausible that strategies to suppress β cell apoptosis and/or increase β cell differentiation/maturation would be effective at improving β cell function. Interestingly, chronic FKN-Fc administration enhanced GSIS and decreased β cell apoptosis.…”

Neuropeptide Y expression marks partially differentiated β cells in mice and humans

“…NPY also marks a highly proliferative insulin -cell-type derived from β cells that contributes to compensatory β cell expansion upon partial pancreatectomy (34). Impairment of β cell maturity contributes to β cell dysfunction in diabetes (17,18,35). Increased NPY in β cells upon diet-induced expansion and preceding diabetes onset in the rodent models suggests that cellular stress rather Regions marked with dotted line show pancreatic ganglia, which also express NPY.…”

Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas

“…BCM is regulated by the balance of newly formed betacells and beta-cell loss. Beta-cell replication and neogenesis are considered to be sources of newlyformed beta-cells, while beta-cell apoptosis is considered a major cause of beta-cell loss [2,49]. A recent rodent study has suggested beta-cell dedifferentiation to be another mechanism of beta-cell loss in diabetes [50].…”