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Measuring rates of biochemical flux in mice following a modified glucose tolerance test.
Author(s) -
Mason Kwynn,
Bederman Ilya,
Gilge Danielle,
Combs Whitney,
Previs Stephen
Publication year - 2006
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.20.4.a595-a
Subject(s) - medicine , endocrinology , glycogen , insulin , glucose homeostasis , insulin resistance , carbohydrate metabolism , glycogen synthase , glucose uptake , carbohydrate , blood sugar regulation , skeletal muscle , glucose tolerance test , cholesterol , homeostasis , metabolism , biology , chemistry
Insulin is an important regulator of glucose homeostasis, e.g. during a glucose challenge insulin stimulates glucose storage in the liver and the skeletal muscle. Since insulin acts on other processes, it is reasonable to expect that the syntheses of lipids and proteins are also stimulated. In cases of “insulin resistance” and Type 2 diabetes, impairments in insulin secretion/action lead to aberrant metabolic regulation. Understanding the extent to which specific pathways are affected by disease affect therapeutic options. We hypothesized that one could determine the rates of synthesis of (i) liver and muscle glycogen, (ii) fatty acids and cholesterol and (iii) proteins by administering 2 H 2 O prior to a modified glucose tolerance test. Healthy C57BL/6J mice were fasted overnight prior to the study. On the morning of the study, mice were injected with 2 H 2 O, randomized to receive an injection of saline (“fasted”) or a mixture of carbohydrate and essential amino acids (“fed”) and killed 3.5 h later. As compared to “fasted” mice, “fed” mice had an increase in the rates of syntheses of total liver glycogen, fatty acids, cholesterol and protein. Although further development and testing are needed, our approach may be useful in determining the metabolic response of carbohydrate, lipid and protein metabolism to a controlled challenge. Application of this method may help to resolve specific impairments in insulin action.