Evaluation of β‐cell mass and function in the Göttingen minipig

Abstract

Increased knowledge about b-cell mass and function is important for our understanding of the pathophysiology of type 2 diabetes (T2DM). The relationship between the two is difficult to study in humans, whereas animal models allow studies of consequences of, for example, reduction of b-cell mass and induction of obesity and procurement of the pancreas for histological examination. An overview of results obtained in the Gö ttingen minipig in relation to b-cell function, and mass is provided here. Effects of a primary reduction of b-cell mass have indicated that not all of the defects of pulsatile insulin secretion in human T2DM can be explained by reduced b-cell mass. Furthermore, induction of obesity has shown deterioration of b-cell function and morphological changes in the pancreas. As in humans, obesity leads to an increased b-cell volume in the minipig, and based on the increased number of islets, neogenesis of islets is an important factor in expansion of b-cell mass in this species. Measurement of b-cell function as an estimate of b-cell mass is, at present, the only method possible in humans, and this approach has been validated using lean and obese minipigs with a range of b-cell mass. The effects on b-cell function and mass of obesity of longer duration and/or more pronounced hyperglycaemia remains to be determined, but the models developed so far represent a valuable tool for such investigations.

Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research

“…In severely obese Göttingen minipigs (w100 kg), beta-cell mass was increased by w2-fold. However, the relative beta-cell mass was significantly reduced in the obese group, indicating that a normal beta-cell mass-to-body weight ratio could not be sustained in response to the largely increased body weight [138]. Similarly, a 1.3-fold increase in beta-cell volume fraction was observed in adult, obese baboons [139].…”

Impact of fetal and neonatal environment on beta cell function and development of diabetes

“…An increasing amount of data suggest that neogenesis and beta cell proliferation are distinct, but not mutually exclusive, pathways executed during pregnancy. The relative contributions may depend on species . Observations by Butler et al.…”

β-Cell Growth and Regeneration: Replication Is Only Part of the Story

“…It should be noted that not all rodent models of β-cell growth show neogenesis: no increases in islet number were seen in pregnancy in mice (12) or in adult ob/ob mice compared with ob /+ controls (13); both of these studies showed increased β-cell mass with larger islets, supporting replication as the mechanism of expansion. One must be aware of possible species differences, as illustrated by neogenesis not being reported in adult mice fed a high-fat diet but reported in adult pigs that became obese after ad libitum feeding for 1–2 years (14). Additionally, in contrast to the data from rodents, the adaptive increase in β-cells during pregnancy in humans is accompanied by decreased mean islet size, increased number of β-cells in “apparently new small islets” with no change in β-cell size, replication, or apoptosis frequency (15).…”