Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy

Abstract

Aims/hypothesisWe sought to establish the extent and basis for adaptive changes in beta cell numbers in human pregnancy.MethodsPancreas was obtained at autopsy from women who had died while pregnant (n = 18), post-partum (n = 6) or were not pregnant at or shortly before death (controls; n = 20). Pancreases were evaluated for fractional pancreatic beta cell area, islet size and islet fraction of beta cells, beta cell replication (Ki67) and apoptosis (TUNEL), and indirect markers of beta cell neogenesis (insulin-positive cells in ducts and scattered beta cells in pancreas).ResultsThe pancreatic fractional beta cell area was increased by ∼1.4-fold in human pregnancy, with no change in mean beta cell size. In pregnancy there were more small islets rather than an increase in islet size or beta cells per islet. No increase in beta cell replication or change in beta cell apoptosis was detected, but duct cells positive for insulin and scattered beta cells were increased with pregnancy.Conclusions/interpretationThe adaptive increase in beta cell numbers in human pregnancy is not as great as in most reports in rodents. This increase in humans is achieved by increased numbers of beta cells in apparently new small islets, rather than duplication of beta cells in existing islets, which is characteristic of pregnancy in rodents.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-010-1809-6) contains supplementary material, which is available to authorised users.

Islet Neogenesis: A Possible Pathway for Beta-Cell Replenishment

“…In adults, the frequencies reported are in the range of 0.4-0.6% insulin-positive duct cells whether in organ donors or autopsied pancreas, although in some pancreata no insulin-positive cells were detectable [58,69,71,72]. The dynamic nature of these insulin-positive cells is suggested by their increase seen in pancreas organs from obese patients [71,72], in patients with chronic pancreatitis [73] during pregnancy [74], and in patients receiving partial pancreatectomy due to recurrent hypoglycemia 1-2 years after gastric bypass [75].…”

“…Butler [74] Donor pancreas (50-yr Medalists with long-term insulin-dependent diabetes) Lobular pattern of single/ doublet insulin -positive cells in parenchyma and in duct epithelium Keenan [82] trophy), and new differentiation from stem/progenitor cells. Yet, β-cell proliferation in adult humans has been reported as extremely low, and greatly enlarged islets are rarely found.…”

Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets

“…The mechanisms responsible for this increase are not fully understood. They have long been considered less reliant on beta cell replication (Butler et al, 2010), although standard replication markers may underestimate human beta cell proliferation rates during post-mortem conditions (Sullivan et al, 2015). Regardless, the existence of progenitors within the pancreas that support the regeneration of functional beta cells is a highly relevant -but controversial -topic in diabetes.…”

Maturation of Stem Cell-Derived Beta-cells Guided by the Expression of Urocortin 3

“…These include the replication of existing beta-cells, the activation of beta-cell neogenesis from endogenous pancreatic progenitors, the transplantation of islet or pancreas tissue of either human or animal origin, and the regeneration and transplantation of beta-cells from stem cells. Human pancreatic beta-cell replication peters out after the neonatal expansion of beta-cell mass [4,5], and unlike in mice, does not increase under obese or pregnant conditions [6,7].…”