Evaluation of beta-cell mass and function in the Göttingen minipig.
Increased knowledge about beta-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 beta-cell mass and induction of obesity and procurement of the pancreas for histological examination. An overview of results obtained in the Göttingen minipig in relation to beta-cell function, and mass is provided here. Effects of a primary reduction of beta-cell mass have indicated that not all of the defects of pulsatile insulin secretion in human T2DM can be explained by reduced beta-cell mass. Furthermore, induction of obesity has shown deterioration of beta-cell function and morphological changes in the pancreas. As in humans, obesity leads to an increased beta-cell volume in the minipig, and based on the increased number of islets, neogenesis of islets is an important factor in expansion of beta-cell mass in this species. Measurement of beta-cell function as an estimate of beta-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 beta-cell mass. The effects on beta-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.
Larsen
M O
MO
Department of GLP-1 and Obesity Pharmacology, Novo Nordisk A/S, Maaloev, Denmark. mmla@novonordisk.com
Rolin
B
B
Raun
K
K
Bjerre Knudsen
L
L
Gotfredsen
C F
CF
Bock
T
T
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D009765:Obesity / Q000473:pathology*; D010179:Pancreas / Q000473:pathology; D013552:Swine; D013556:Swine, Miniature
D007328:Insulin