The Role of Insulin in Human Brain Glucose Metabolism

Abstract

The effect of basal insulin on global and regional brain glucose uptake and metabolism in humans was studied using 18-fluorodeoxyglucose and positron emission tomography (FDG-PET). Eight healthy male volunteers aged 49.3 +/- 5.1 years were studied twice in random order. On each occasion, they received an infusion of 0.1 mg. kg(-1). min(-1) somatostatin to suppress endogenous insulin production. In one study 0.3 mU. kg(-1). min(-1) insulin was infused to replace basal circulating insulin levels, and in the other study a saline infusion was used as control. We sought stimulatory effects of basal insulin on brain glucose metabolism particularly in regions with deficiencies in the blood-brain barrier and high density of insulin receptors. Insulin levels were 27.07 +/- 1.3 mU/l with insulin replacement and 3.51 +/- 0.4 mU/l without (P = 0.001). Mean global rate of brain glucose utilization was 0.215 +/- 0.030 mmol. kg(-1). min(-1) without insulin and 0.245 +/- 0.021 mmol. kg(-1). min(-1) with insulin (P = 0.008, an average difference of 15.3 +/- 12.5%). Regional analysis using statistical parametric mapping showed that the effect of basal insulin was significantly less in the cerebellum (Z = 5.53, corrected P = 0.031). We conclude that basal insulin has a role in regulating global brain glucose uptake in humans, mostly marked in cortical areas.

Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System

“…Insulin crosses the blood-brain barrier via the saturable transport system (19). Some studies in subjects with normal glucose tolerance have failed to show any effect of insulin on brain glucose metabolism (20), whereas other studies have demonstrated that insulin increases CMR glu (21). However, in our study, the rise in plasma insulin and glucose concentrations after EX was reduced compared with PLC, making this an unlikely explanation for the increase in CMR glu .…”

Obese men respond to cognitive but not to catabolic brain insulin signaling

“…27 The slow onset of memory enhancement by intranasal insulin in the absence of acute effects speaks for the involvement of gradual plastic neuronal changes. Enhancement of neuronal glucose utilization by insulin 29 as well as the observed suppression of cortisol release may have further supported memory improvement. 30 Glucocorticoids can inhibit synaptic long-term potentiation and decrease hippocampal glutamate turnover by binding to hippocampal glucocorticoid receptors.…”

Role for neuronal insulin resistance in neurodegenerative diseases

“…More recently, it has been demonstrated that the related IGF-1 is required for brain glucose metabolism in mice (29). In humans it has been demonstrated that insulin acutely regulates brain glucose metabolism during euglycemic hyperinsulinemic clamp studies (30), and by using labeled 2-deoxyglucose we have found decreased glucose uptake in brains of NIRKO mice during a euglycemic hyperinsulinemic clamp (S. Fisher, J.C.B., and C.R.K., unpublished data). In the present study, steady-state brain glucose metabolism under basal conditions, as assessed by PET imaging in NIRKO mice in vivo, was normal.…”