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Effects of insulin and amyloid β 1–42 oligomers on glucose incorporation and mitochondrial function in cultured rat hippocampal neurons
Author(s) -
Miichi Yoshiaki,
Sakurai Takashi,
Akisaki Taichi,
Yokono Koichi
Publication year - 2011
Publication title -
geriatrics and gerontology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 57
eISSN - 1447-0594
pISSN - 1444-1586
DOI - 10.1111/j.1447-0594.2011.00712.x
Subject(s) - hexokinase , insulin , hippocampal formation , medicine , glucose transporter , glucose uptake , carbohydrate metabolism , adenosine triphosphate , insulin receptor , endocrinology , glucose homeostasis , metabolism , homeostasis , biochemistry , chemistry , biology , glycolysis , insulin resistance
Aim: The molecular basis for impaired glucose metabolism in patients with Alzheimer's disease (AD) has not been fully clarified. We tested whether insulin and amyloid (A)β 1–42 oligomers would regulate glucose metabolism and energy homeostasis directly in cultured rat hippocampal neurons and evaluated possible interactions between insulin signaling and Aβ 1–42 oligomers. Methods: Dissociated hippocampal neurons were prepared from Wistar rat embryos at day 21 of gestation and cultured for 14 days. Cultured neurons were exposed to insulin (1 µM) for 30 min, and Aβ 1–42 oligomers (1 µM) were added to culture media for 10–30 min. The glucose uptake of cultured neurons was measured by enzymatic fluorescence assay using 2‐deoxy‐d‐glucose (2DG), and adenosine triphosphate (ATP) contents were quantified using a luciferin/luciferase luminescence assay. Results: Aβ 1–42 oligomers did not suppress 2DG uptake, reflecting the activities of glucose transporters and/or hexokinase, but led to disrupted ATP contents in the presence and absence of monocarboxylates (lactate/pyruvate). Insulin and C‐peptide did not change glucose uptake or ATP concentrations. Conclusion: The primary target of Aβ 1–42 oligomers might be mitochondria, which could explain the reduced cerebral glucose levels in patients with AD. Moreover, insulin signaling was not directly linked to glucose metabolism or energy homeostasis in cultured rat hippocampal neurons. Geriatr Gerontol Int 2011; 11: 517–524.