Apoptosis Participates in the Remodeling of the Endocrine Pancreas in the Neonatal Rat

Abstract

In rodents, shortly after birth a lack of increase in pancreatic weight and in islet mass have been reported during a time of overall body weight increase. To understand this regulation of the neonatal growth of the beta cell mass, we studied Sprague Dawley rats at 2, 9, 13, 17, 20, 24, and 31 days of age for beta cell replication, beta cell mass, and cell size and for the presence of cell apoptosis. beta cell mass was stable from 2-20 days (range: 0.91 +/- 0.2 to 1.33 +/- 0.23 mg) and increased thereafter. beta cell replication progressively decreased. Condensed apoptotic nuclei were identified and counted on paraffin sections using the fluorescent dye propidium iodide. Apoptotic beta cell nuclei were found at a basal rate (1.54 +/- 0.22%) at 2, 9, and again after 20 days of age. However, at 13 and 17 days, the incidence of apoptosis was significantly increased (3.64 +/- 0.45%). The decreased replication and the increased incidence of apoptosis in the beta cells strongly suggest a wave of neogenesis of beta cells to maintain the constant beta cell mass. These data show that the endocrine pancreas undergoes significant modification during neonatal life and that apoptosis is an important mechanism in this remodeling of the beta cell mass. Whether a selective deletion of some population of beta cells occurs is unclear, but a dysregulation of this remodeling process could have important effects on the pancreatic beta cell mass.

Mechanisms of action of glucagon-like peptide 1 in the pancreas

“…GLP-1R activation has been demonstrated both in human islets in vitro and in rodent models in vivo to reduce β cell apoptosis. The rate of β cell apoptosis is very low (Scaglia et al, 1997) and therefore models of injury to the endocrine pancreas have to be used to measure potential protective effects of GLP-1R agonists against the demise of the β cell. The first published model was the inbred Zucker diabetic fatty rat (ZDF/GmiTM-fa/fa, previously described in section 6.1) to which GLP-1 was infused over 2 days (Farilla et al, 2002).…”

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

“…In rodents, the endocrine cell population undergoes a dramatic expansion beginning at embryonic day 14.5 followed by remodelling, during which there is regulated alteration in apoptosis and neogenesis and a progressive decrease in beta cell replication [16].…”

Fetal programming of glucose–insulin metabolism

“…It has been demonstrated in the low protein model that islet vascularisation was dramatically reduced in neonates of low protein dams (37) as was the number and volume density Page 11 of 21 A c c e p t e d M a n u s c r i p t 11 (38). Shortly after birth a wave of apoptosis and remodelling of the beta cells occurs (67,68). It has now been shown that new beta cells arise from the proliferation of existing beta cells (69) as well as differentiating acinar cells (70).…”