title: Topologically heterogeneous beta cell adaptation in response to high-fat diet in mice.
abstract: OBJECTIVE
  Beta cells adapt to an increased insulin demand by enhancing insulin secretion via increased beta cell function and/or increased beta cell number. While morphological and functional heterogeneity between individual islets exists, it is unknown whether regional differences in beta cell adaptation occur. Therefore we investigated beta cell adaptation throughout the pancreas in a model of high-fat diet (HFD)-induced insulin resistance in mice.
  
  
  METHODS
  C57BL/6J mice were fed a HFD to induce insulin resistance, or control diet for 6 weeks. The pancreas was divided in a duodenal (DR), gastric (GR) and splenic (SR) region and taken for either histology or islet isolation. The capacity of untreated islets from the three regions to adapt in an extrapancreatic location was assessed by transplantation under the kidney capsule of streptozotocin-treated mice.
  
  
  RESULTS
  SR islets showed 70% increased beta cell proliferation after HFD, whereas no significant increase was found in DR and GR islets. Furthermore, isolated SR islets showed twofold enhanced glucose-induced insulin secretion after HFD, as compared with DR and GR islets. In contrast, transplantation of islets isolated from the three regions to an extrapancreatic location in diabetic mice led to a similar decrease in hyperglycemia and no difference in beta cell proliferation.
  
  
  CONCLUSIONS
  HFD-induced insulin resistance leads to topologically heterogeneous beta cell adaptation and is most prominent in the splenic region of the pancreas. This topological heterogeneity in beta cell adaptation appears to result from extrinsic factors present in the islet microenvironment.
authors: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Johanne H
authors: JH
authors: Ellenbroek
authors: Hendrica A
authors: HA
authors: Töns
authors: Natascha
authors: N
authors: de Graaf
authors: Cindy J
authors: CJ
authors: Loomans
authors: Marten A
authors: MA
authors: Engelse
authors: Hans
authors: H
authors: Vrolijk
authors: Peter J
authors: PJ
authors: Voshol
authors: Ton J
authors: TJ
authors: Rabelink
authors: Françoise
authors: F
authors: Carlotti
authors: Eelco J
authors: EJ
authors: de Koning
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D049109:Cell Proliferation; D059305:Diet, High-Fat; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D008297:Male; D051379:Mice; D010179:Pancreas / Q000378:metabolism
chemical_list: D007328:Insulin; D005947:Glucose