Regional Differences in Cerebral Blood Flow and Glucose Utilization in Diabetic Man: The Effect of Insulin

Abstract

To determine the effect of insulin on regional cerebral blood flow (rCBF) and glucose metabolism (CMRglu), we performed quantitative dynamic PET scanning of labeled water (H215O) and deoxyglucose (18FDG) using two protocols in 10 diabetic men. In protocol A, to test reproducibility of the technique, insulin was infused at 1.5 mU·kg−1·min−1 twice (n = 5). In protocol B, low (0.3 mU·kg−1·min−1) and high (3 mU·kg−1·min−1) dose insulin was given on separate occasions (n = 5). Euglycemia (5 mmol/L) was maintained by glucose infusion. In protocol A, CMRglu was 6% higher during the first infusion, and catecholamines were also increased, indicating stress. Blood flow was not different. Changing free insulin levels from 20.5 ± 4.8 to 191 ± 44.5 mU/L ( P < 0.001, low versus high dose, protocol B) did not alter total or regional CMRglu (whole brain 36.6 ± 4.0 versus 32.8 ± 6.2 μmol·100 g−1·min−1, P = 0.32) or CBF (41.7 ± 5.1 and 45.6 ± 9.7 mL·100 g−1·min−1, P = 0.4) or rCBF. In cerebellum, CMRglu was lower than in cortex and the ratio between rate constants for glucose uptake and phosphorylation ( K1 and k3) was reversed. There are regional differences in cerebral metabolic capacity that may explain why cerebral cortex is more sensitive to hypoglycemia than cerebellum. Brain glucose metabolism is not sensitive to insulin concentration within the physiologic range. This suggests that intracerebral insulin receptors have a different role from those in the periphery.