Brain glucose overexposure and lack of acute metabolic flexibility in obesity and type 2 diabetes: a PET-[18F]FDG study in Zucker and ZDF rats

Abstract

Brain glucose exposure may complicate diabetes and obesity. We used positron emission tomography with (18)F-fluorodeoxyglucose in Zucker obese, diabetic, and control rats to determine the contributions of blood glucose mass action versus local mechanisms in regulating central glucose disposal in fasted and acutely glucose-stimulated states, and their adaptations in obesity and diabetes. Our study data indicate that brain glucose uptake is dependent on both local and mass action components, and is stimulated by acute glucose intake in healthy rats. In diseased animals, the organ was chronically overexposed to glucose, due to high fasting glucose uptake, almost abolishing the physiologic response to glucose loading.

Figure 1

(A) Design of a positron emission tomography (PET) study session. (B) Areas under the blood tracer concentration curve (input function) after correcting for individually measured or averaged spillover fractions in 20 animals undergoing frequent blood sampling, showing no difference (left) and a tight correlation (right) between the two methods.