title: Increased β-cell volume in mice fed a high-fat diet: a dynamic study over 12 months.
abstract: As we previously demonstrated, there is an adaptive increase in insulin secretion in insulin resistance in the model of high-fat fed female mice. Since it is assumed that islets also adapt to insulin resistance with β-cell expansion, we have now examined beta volume in this experimental model. Female C57BL/6JBomTac mice were therefore fed a high-fat diet (60% fat from lard) for three, six or twelve months and beta cell volume was estimated as β-cell area per islet, individual β-cell size, and β-cell number per islet. Control animals were fed a normal chow (11% fat). We found that β-cell area per islet and total number of beta cells per islet were increased already after three months of high-fat feeding and that this increase was sustained throughout the twelve month study period. In contrast, individual beta cell size showed a dynamic pattern with a reduction after three months followed by increase after six and twelve months. The number of apoptosis (caspase-3) positive β-cells was reduced after three months, whereas there was no difference in proliferation (Ki-67) positive cells, although these were generally rarely observed. Thus, we conclude that insulin resistance accompanying high-fat feeding in mice is followed by progressive β-cell expansion as evident by early increased islet β-cell volume and total number of β-cells, whereas individual β-cell size showed a dynamic response. The model is also associated with an early reduced apoptosis, which may contribute to the increased beta cell volume.
authors.affiliation: Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Ahrén
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.forename: Nils
authors.initials: N
authors.lastname: Wierup
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D048429:Cell Size; D004041:Dietary Fats / Q000009:adverse effects*; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D011236:Prediabetic State / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D004041:Dietary Fats; C505409:Casp3 protein, mouse; D053148:Caspase 3