Brain Glucose Transport and Phosphorylation Under Acute Insulin-Induced Hypoglycemia in Mice: An 18F-FDG PET Study
| Autor: | Malte F. Alf, João M. N. Duarte, Stefanie D. Krämer, Rolf Gruetter, Roger Schibli |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Hypoglycemia Blood–brain barrier Michaelis–Menten kinetics ddc:616.0757 Permeability Mice Fluorodeoxyglucose F18 CIBM-PET Internal medicine brain glucose metabolism medicine Animals Insulin Radiology Nuclear Medicine and imaging Phosphorylation Michaelis-Menten kinetics CIBM-AIT business.industry Glucose transporter Brain Biological Transport medicine.disease Kinetics Glucose medicine.anatomical_structure Endocrinology Cerebral blood flow Blood-Brain Barrier Organ Specificity Cerebrovascular Circulation Positron-Emission Tomography business Intracellular |
| Zdroj: | Journal of Nuclear Medicine, Vol. 54, No 12 (2013) pp. 2153-2160 |
| ISSN: | 0161-5505 |
| Popis: | We addressed the questions of how cerebral glucose transport and phosphorylation change under acute hypoglycemia and what the underlying mechanisms of adaptation are. Methods: Quantitative 18F-FDG PET combined with the acquisition of real-time arterial input function was performed on mice. Hypoglycemia was induced and maintained by insulin infusion. PET data were analyzed with the 2-tissue-compartment model for 18F-FDG, and the results were evaluated with Michaelis–Menten saturation kinetics. Results: Glucose clearance from plasma to brain (K1,glc) and the phosphorylation rate constant increased with decreasing plasma glucose (Gp), in particular at a Gp of less than 2.5 mmol/L. Estimated cerebral glucose extraction ratios taking into account an increased cerebral blood flow (CBF) at a Gp of less than 2 mmol/L were between 0.14 and 0.79. CBF-normalized K1,glc values were in agreement with saturation kinetics. Phosphorylation rate constants indicated intracellular glucose depletion at a Gp of less than 2–3 mmol/L. When brain regions were compared, glucose transport under hypoglycemia was lowest in the hypothalamus. Conclusion: Alterations in glucose transport and phosphorylation, as well as intracellular glucose depletion, under acute hypoglycemia can be modeled by saturation kinetics taking into account an increase in CBF. Distinct transport kinetics in the hypothalamus may be involved in its glucose-sensing function. |
| Databáze: | OpenAIRE |
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