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Non‐invasive quantification of brain glycogen absolute concentration
Author(s) -
Morgenthaler Florence D.,
Van Heeswijk Ruud B.,
Xin Lijing,
Laus Sabrina,
Frenkel Hanne,
Lei Hongxia,
Gruetter Rolf
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05717.x
Subject(s) - glycogen , in vivo , glycogen synthase , glycogen branching enzyme , glycogenesis , insulin , chemistry , endocrinology , medicine , biochemistry , biology , microbiology and biotechnology
The only currently available method to measure brain glycogen in vivo is 13 C NMR spectroscopy. Incorporation of 13 C‐labeled glucose (Glc) is necessary to allow glycogen measurement, but might be affected by turnover changes. Our aim was to measure glycogen absolute concentration in the rat brain by eliminating label turnover as variable. The approach is based on establishing an increased, constant 13 C isotopic enrichment (IE). 13 C‐Glc infusion is then performed at the IE of brain glycogen. As glycogen IE cannot be assessed in vivo , we validated that it can be inferred from that of N ‐acetyl‐aspartate IE in vivo: After [1‐ 13 C]‐Glc ingestion, glycogen IE was 2.2 ± 0.1 fold that of N ‐acetyl‐aspartate ( n = 11, R 2 = 0.77). After subsequent Glc infusion, glycogen IE equaled brain Glc IE ( n = 6, paired t ‐test, p = 0.37), implying isotopic steady‐state achievement and complete turnover of the glycogen molecule. Glycogen concentration measured in vivo by 13 C NMR (mean ± SD: 5.8 ± 0.7 μmol/g) was in excellent agreement with that in vitro (6.4 ± 0.6 μmol/g, n = 5). When insulin was administered, the stability of glycogen concentration was analogous to previous biochemical measurements implying that glycogen turnover is activated by insulin. We conclude that the entire glycogen molecule is turned over and that insulin activates glycogen turnover.