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Marked Hyperfructosemia without Fructose‐Induced Hyperglycemia and Diabetes in Fructokinase‐deficient Mice
Author(s) -
Patel C,
Sugimoto K,
Shah A,
Parikh S,
Douard V,
Inui H,
Yamanouchi T,
Ferraris R
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1009.1
Subject(s) - fructokinase , medicine , endocrinology , postprandial , fructose , glucose homeostasis , diabetes mellitus , chemistry , homeostasis , biology , metabolism , insulin resistance , biochemistry
Management of fructose (F)‐linked metabolic disorders requires an understanding of F homeostasis, yet the important roles of dietary F, of the F transporter GLUT5, and of fructokinase (FK) in simultaneously regulating serum levels of F have not been studied. Wildtype (WT) and FK‐/‐ mice were fed for 7 d isocaloric 0% or 20% F diets, fasted overnight, then killed 0 to 7.5 h after initial feeding at the onset of the dark phase when feeding activity was greatest. Analysis by HPLC showed portal and systemic F levels in WT mice fed 0% F to be < 0.1 mM, similar to those of GLUT5‐/‐ mice naively fed F, and independent of time after feeding. WT mice consuming 20% F had fasting serum F levels similar to, and postprandial levels 3‐fold greater than, those eating 0% F. Deletion of FK resulted in ~80‐fold greater serum F levels (~4 mM) than those in WT and GLUT5‐/‐ mice. In FK‐/‐ mice fed 20% F, systemic was paradoxically ~2‐fold greater than portal serum F, suggesting that F accumulated in the systemic circulation. Significant F‐induced hyperglycemia in WT mice was prevented by FK deletion. Systemic serum F levels remained low (< 0.05 mM) in WT after chronic consumption ad libitum of 0 or 20 % F for 12 wk, but increased to > 1 mM in phenotypically normal FK‐/‐ mice. The chronic F‐induced hyperglycemia in WT, but not the chronic hyperfructosemia in FK‐/‐ mice, increased in HbA1c levels. Finally, in WT, GLUT5‐/‐ and FK‐/‐ mice fed 0% F, there seems to be a FK‐ and GLUT5‐independent, significant endogenous synthesis of F. FK is required to prevent hyperfructosemia as well as F‐induced hyperglycemia and diabetes (NSF1121049).