At the centennial of Michaelis and Menten, competing Michaelis-Menten steps explain effect of GLP-1 on blood-brain transfer and metabolism of glucose

Michael Gejl, Jørgen Rungby, Birgitte Brock, Albert Gjedde

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)162-171
Number of pages10
JournalBasic and Clinical Pharmacology and Toxicology
Volume115
Issue number2
DOIs
StatePublished - 2014

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Glucagon-Like Peptide 1
Metabolism
Brain
Blood
Glucose
Neurodegenerative Diseases
Blood Glucose
Stroke
Incretins
Appetite Regulation
Enzyme kinetics
Autonomic Nervous System
Neurology
Appetite
Enzymes
Medical problems
Type 2 Diabetes Mellitus
Energy Metabolism
Pancreas
Chemical activation

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Medicine(all)

Cite this

At the centennial of Michaelis and Menten, competing Michaelis-Menten steps explain effect of GLP-1 on blood-brain transfer and metabolism of glucose. / Gejl, Michael; Rungby, Jørgen; Brock, Birgitte; Gjedde, Albert.

In: Basic and Clinical Pharmacology and Toxicology, Vol. 115, No. 2, 2014, p. 162-171.

Research output: Contribution to journalArticle

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