title: Dietary-fat-induced obesity in mice results in beta cell hyperplasia but not increased insulin release: evidence for specificity of impaired beta cell adaptation.
abstract: OBJECTIVE
  Increased dietary fat intake is associated with obesity and insulin resistance, but studies have shown that the subsequent increase in insulin release is not appropriate for this obesity-induced insulin resistance. We therefore sought to determine whether the impaired beta cell adaptation is due to inadequate expansion of the beta cell population or to a lack of an adaptive increase in insulin release.
  
  
  METHODS
  Male mice were fed diets containing increasing amounts of fat (15, 30 or 45% of energy intake) for 1 year, after which islet morphology and secretory function were assessed.
  
  
  RESULTS
  Increased dietary fat intake was associated with a progressive increase in body weight (p<0.001). Fractional beta cell area (total beta cell area/section area) was increased with increasing dietary fat (1.36+/-0.39, 2.46+/-0.40 and 4.93+/-1.05%, p<0.001), due to beta cell hyperplasia, and was positively and highly correlated with body weight (r2=0.68, p<0.005). In contrast, insulin release following i.p. glucose did not increase with increasing dietary fat (118+/-32, 108+/-47 and 488+/-200 pmol/l per mmol/l, p=0.07) and did not correlate with body weight (r2=0.11). When this response was examined relative to fractional beta cell area (insulin release/fractional beta cell area), it did not increase but rather tended to decrease with increasing dietary fat (157+/-55, 43+/-13 and 97+/-53 [pmol/l per mmol/l]/%, p=0.06) and did not correlate with body weight (r2=0.02).
  
  
  CONCLUSIONS
  Long-term fat feeding is associated with an increase in the beta cell population but an inadequate functional adaptation. Thus, a functional rather than a morphological abnormality appears to underlie dietary-fat-induced beta cell dysfunction.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System (151), University of Washington, 1660 S. Columbian Way, Seattle, WA 98108, USA. rhull@u.washington.edu
authors.forename: R L
authors.initials: RL
authors.lastname: Hull
authors.forename: K
authors.initials: K
authors.lastname: Kodama
authors.forename: K M
authors.initials: KM
authors.lastname: Utzschneider
authors.forename: D B
authors.initials: DB
authors.lastname: Carr
authors.forename: R L
authors.initials: RL
authors.lastname: Prigeon
authors.forename: S E
authors.initials: SE
authors.lastname: Kahn
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000494:pharmacology*; D006965:Hyperplasia; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin