Dietary-fat-induced obesity in mice results in beta cell hyperplasia but not increased insulin release: evidence for specificity of impaired beta cell adaptation.

Autor: Hull, R. L., Kodama, K., Utzschneider, K. M., Carr, D. B., Prigeon, R. L., Kahn, S. E.
Předmět:
Zdroj: Diabetologia; Jul2005, Vol. 48 Issue 7, p1350-1358, 9p
Abstrakt: Aims/hypothesis: 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 conelate with body weight (r²=0.02). Conclusions/interpretation: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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