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At the Centennial of Michaelis and Menten, Competing Michaelis–Menten Steps Explain Effect of GLP ‐1 on Blood–Brain Transfer and Metabolism of Glucose
Author(s) -
Gejl Michael,
Rungby Jørgen,
Brock Birgitte,
Gjedde Albert
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12240
Subject(s) - neuroprotection , incretin , endocrinology , carbohydrate metabolism , michaelis–menten kinetics , metabolism , medicine , glucagon like peptide 1 , glucose homeostasis , dipeptidyl peptidase , diabetes mellitus , receptor , biology , enzyme , biochemistry , type 2 diabetes , enzyme assay , insulin resistance
Glucagon‐like peptide‐1 ( GLP ‐1) is a potent insulinotropic incretin hormone with both pancreatic and extrapancreatic effects. Studies of GLP‐1 reveal significant effects in regions of brain tissue that regulate appetite and satiety. GLP‐1 mimetics are used for the treatment of type 2 diabetes mellitus. GLP ‐1 interacts with peripheral functions in which the autonomic nervous system plays an important role, and emerging pre‐clinical findings indicate a potential neuroprotective role of the peptide, for example in models of stroke and in neurodegenerative disorders. A century ago, Leonor Michaelis and Maud Menten described the steady‐state enzyme kinetics that still apply to the multiple receptors, transporters and enzymes that define the biochemical reactions of the brain, including the glucose‐dependent impact of GLP ‐1 on blood–brain glucose transfer and metabolism. This MiniReview examines the potential of GLP ‐1 as a molecule of interest for the understanding of brain energy metabolism and with reference to the impact on brain metabolism related to appetite and satiety regulation, stroke and neurodegenerative disorders. These effects can be understood only by reference to the original formulation of the Michaelis–Menten equation as applied to a chain of kinetically controlled steps. Indeed, the effects of GLP ‐1 receptor activation on blood–brain glucose transfer and brain metabolism of glucose depend on the glucose concentration and relative affinities of the steps both in vitro and in vivo , as in the pancreas.