Islet β cell mass in diabetes and how it relates to function, birth, and death

Abstract

In type 1 diabetes (T1D) β cell mass is markedly reduced by autoimmunity. Type 2 diabetes (T2D) results from inadequate β cell mass and function that can no longer compensate for insulin resistance. The reduction of β cell mass in T2D may result from increased cell death and/or inadequate birth through replication and neogenesis. Reduction in mass allows glucose levels to rise, which places β cells in an unfamiliar hyperglycemic environment, leading to marked changes in their phenotype and a dramatic loss of glucose-stimulated insulin secretion (GSIS), which worsens as glucose levels climb. Toxic effects of glucose on β cells (glucotoxicity) appear to be the culprit. This dysfunctional insulin secretion can be reversed when glucose levels are lowered by treatment, a finding with therapeutic significance. Restoration of β cell mass in both types of diabetes could be accomplished by either β cell regeneration or transplantation. Learning more about the relationships between β cell mass, turnover, and function and finding ways to restore β cell mass are among the most urgent priorities for diabetes research.

Figure 1

β cell relative volume in autopsy pancreases from individuals who were nondiabetic (ND) had impaired fasting glucose (IFTG) or had type 2 diabetes mellitus (TTDM). Figure taken from Ref. , with permission from the American Diabetes Association.

Figure 2

Increments of acute GSIS in subjects with increasing fasting plasma glucose levels. Figure taken from Ref. , with permission from the Endocrine Society.

Figure 3

Subjects with noninsulin-dependent diabetes (NIDDM, T2D) and control subjects whose glucose levels were increased with glucose infusions followed by acute stimulation of insulin secretion with intravenous arginine. Figure taken from Ref. , with permission from the Endocrine Society.

Figure 4

Section of pancreas (20× magnification) stained for insulin. Numerous pancreatic ducts are shown, with insulin-positive cells present in and next to duct wall, suggesting new islet formation from exocrine ducts (neogenesis). Figure taken from Ref. , with permission from the American Diabetes Association.