Dietary-fat-induced obesity in mice results in beta cell hyperplasia but not increased insulin release: evidence for specificity of impaired beta cell adaptation.
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.
Hull
R L
RL
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
Kodama
K
K
Utzschneider
K M
KM
Carr
D B
DB
Prigeon
R L
RL
Kahn
S E
SE
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
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin