Effects of insulin on brain glucose metabolism in impaired glucose tolerance

Abstract

Objective: Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance.

Research design and methods: We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [(18)F]fluorodeoxyglucose (for brain glucose metabolism) and [(15)O]H(2)O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling.

Results: The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group.

Conclusions: We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance.

FIG. 1.

The percentage of the insulin-stimulated increase in brain glucose metabolism is higher in subjects with impaired glucose tolerance. The increase in brain glucose metabolism in patients with impaired glucose tolerance was similar across brain regions, ranging from 16% in the cerebellum to 23% in the thalamus. Error bars represent the SEM.

FIG. 2.

Results from the voxel-based statistical parametric mapping analysis, demonstrating a higher insulin-stimulated increase in brain glucose metabolism in subjects with impaired glucose tolerance than in healthy subjects. A: An exploratory analysis with voxel-level uncorrected P < 0.05 revealed a large cluster that encompasses most gray matter regions in the brain. B: Stricter analysis with voxel-level uncorrected P < 0.001 demonstrating the most significant difference localized in the right posterior insula (T_max = 5.39 at [40, −26, 14], k_E = 116,567 voxels, cluster-level corrected P < 0.001). Color scale represents the T value at the voxel level.