Emma Bingham

Lactate: A Preferred Fuel for Human Brain Metabolism in Vivo

Recent in vitro studies suggest that lactate, rather than glucose, may be the preferred fuel for neuronal metabolism. The authors examined the effect of lactate on global brain glucose uptake in euglycemic human subjects using 18fluorodeoxyglucose (FDG) positron emission tomography (PET). Eight healthy men, aged 40 to 54 years, underwent a 60-minute FDG-PET scan on two occasions in random order. On one occasion, 6.72% sodium lactate was infused at a rate of 50 μmol · kg−1 · min−1 for 20 minutes and then reduced to 30 μmol · kg−1 · min−1; 1.4% sodium bicarbonate was infused as a control on the other occasion. Plasma glucose levels were not different between the two groups (5.3 ± 0.23 and 5.3 ± 0.24 mmol/L, P = 0.55). Plasma lactate was significantly elevated by lactate infusion (4.08 ± 0.35 vs. 0.63 ± 0.22 mmol/L, P < 0.0005. The whole-brain rate of glucose uptake was significantly reduced by approximately 17% during lactate infusion (0.195 ± 0.022 vs. 0.234 ± 0.020 μmol · g−1 · min−1, P = 0.001). The authors conclude that, in vivo in humans, circulating lactate is used by the brain at euglycemia, with sparing of glucose.

Attenuation of Insulin-Evoked Responses in Brain Networks Controlling Appetite and Reward in Insulin Resistance The Cerebral Basis for Impaired Control of Food Intake in Metabolic Syndrome?

The rising prevalence of obesity and type 2 diabetes is a global challenge. A possible mechanism linking insulin resistance and weight gain would be attenuation of insulin-evoked responses in brain areas relevant to eating in systemic insulin resistance. We measured brain glucose metabolism, using [18F]fluorodeoxyglucose positron emission tomography, in seven insulin-sensitive (homeostasis model assessment of insulin resistance [HOMA-IR] = 1.3) and seven insulin-resistant (HOMA-IR = 6.3) men, during suppression of endogenous insulin by somatostatin, with and without an insulin infusion that elevated insulin to 24.6 ± 5.2 and 23.2 ± 5.8 mU/l (P = 0.76), concentrations similar to fasting levels of the resistant subjects and approximately threefold above those of the insulin-sensitive subjects. Insulin-evoked change in global cerebral metabolic rate for glucose was reduced in insulin resistance (+7 vs. +17.4%, P = 0.033). Insulin was associated with increased metabolism in ventral striatum and prefrontal cortex and with decreased metabolism in right amygdala/hippocampus and cerebellar vermis (P < 0.001), relative to global brain. Insulin’s effect was less in ventral striatum and prefrontal cortex in the insulin-resistant subjects (mean ± SD for right ventral striatum 3.2 ± 3.9 vs. 7.7 ± 1.7, P = 0.017). We conclude that brain insulin resistance exists in peripheral insulin resistance, especially in regions subserving appetite and reward. Diminishing the link be-tween control of food intake and energy balance may contribute to development of obesity in insulin resistance.

The effects of KATP channel modulators on counterregulatory responses and cognitive function during acute controlled hypoglycaemia in healthy men: a pilot study

Aims To examine the effects of agents that alter potassium adenosine triphosphate (KATP) channel activity in β‐cells on cognitive function and counterregulatory hormone responses during acute hypoglycaemia, given the physiological similarities between the pancreatic β‐cell and the hypothalamic glucose‐sensitive neurones (GSN) and the widespread distribution of sulphonylurea receptors in neuronal cells throughout the brain.