Changes of glucose transporters in the cerebral adaptation to hypoglycemia

Lee, Dong Hoon; Chung, Min Young; Lee, Jong Un; Kang, Dae Gill; Paek, Yun Woong

doi:10.1016/s0168-8227(99)00107-2

Cited by 42 publications

(30 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies in animal brain exposed to prolonged hypoglycemia (which would be expected to induce counter-regulatory failure comparable to that shown by our hypoglycemia-unaware patients) have shown increased expression of the glucose transporters GLUT1 and GLUT3 (31,32). Therefore, the reduction in FDG uptake in our unaware group might have reflected a change either in glucose phosphorylation or in the lumped constant, rather than in glucose uptake.…”

Section: Fdg-pet In Counter-regulatory Failuresupporting

confidence: 66%

Changes in Regional Brain 18F-Fluorodeoxyglucose Uptake at Hypoglycemia in Type 1 Diabetic Men Associated With Hypoglycemia Unawareness and Counter-Regulatory Failure

et al. 2001

View full text Add to dashboard Cite

We examined the effects of acute moderate hypoglycemia and the condition of hypoglycemia unawareness on regional brain uptake of the labeled glucose analog [ 18 F]fluorodeoxyglucose (FDG) using positron emission tomography (PET). FDG-PET was performed in diabetic patients with (n ‫؍‬ 6) and without (n ‫؍‬ 7) hypoglycemia awareness. Each patient was studied at plasma glucose levels of 5 and 2.6 mmol/l, applied by glucose clamp techniques, in random order. Hypoglycemia-unaware patients were asymptomatic during hypoglycemia, with S ymptomatic awareness of minor hypoglycemia is the diabetic patient's main defense against more profound falls in plasma glucose concentrations, to levels low enough to disturb cognitive function. Loss of the ability to recognize early hypoglycemia (hypoglycemia unawareness) is associated with increased incidence of severe hypoglycemia, with sudden confusion or coma (1). Fear of such hypoglycemia limits attempts to maintain strict glycemic control (2), despite clear evidence of its long-term benefits (3).Hypoglycemia unawareness is associated with defects in the normal protective responses to a falling plasma glucose concentration (4). A greater degree of hypoglycemia is required to trigger hormonal and autonomic responses, and the magnitude of responses at any given glucose level is reduced (5). Detection of hypoglycemia and the initiation of counter-regulation is a brain function, and it is suggested that some alteration of brain function at hypoglycemia underlies the defective counter-regulation of hypoglycemia unawareness (6). The effect of hypoglycemia unawareness on the glucose levels associated with the onset of cognitive dysfunction during hypoglycemia in hypoglycemia-unaware patients is controversial, as cognitive functions are differently sensitive to hypoglycemia and show variable changes in sensitivity to hypoglycemia in hypoglycemia unawareness (7,8). This led us to formulate the hypothesis that there would be regional differences in the brain's metabolic responses to acute hypoglycemia between hypoglycemia-aware and -unaware patients.To investigate this, we performed [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scans in diabetic men with and without hypoglycemia awareness at euglycemia and hypoglycemia. FDG is an analog of natural glucose (deoxyglucose), labeled with a positron emitter, 18 F. Deoxyglucose is taken up by cells and phosphorylated but then proceeds no further along the intracellular glucose metabolic pathway. Accumulation of labeled deoxyglucose in tissue cells has long been used as a way of measuring glucose uptake in tissue and initial metabolism in many tissues, including the brain (9) The effect of moderate hypoglycemia on the factor (the lumped constant) used to relate the rate of FDG uptake to that of native glucose is uncertain (10). Thus it is not valid, for example, to interpret changes in the rate of wholebrain FDG uptake in hypoglycemia as directly proportional to change in the rate of glucose uptake. The analysis we present her...

show abstract

Section: Fdg-pet In Counter-regulatory Failuresupporting

confidence: 66%

Changes in Regional Brain 18F-Fluorodeoxyglucose Uptake at Hypoglycemia in Type 1 Diabetic Men Associated With Hypoglycemia Unawareness and Counter-Regulatory Failure

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Glut3 levels in neurons were found to initially increase following ischemic injury but at latter time points levels were found to have dramatically decreased corresponding with neuronal cell death (Vannucci et al, 1998). Hypoglycemia has also been shown to induce a dramatic and sustained global increase in neuronal expression of Glut3 (Duelli et al, 1999;Lee et al, 2000). Interestingly, the highest sustained levels of neuronal Glut3 expression appear to be in hypoglycemic models that actually promote large fluctuations in glycemic levels.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of Neuronal Glucose Transporter 3 but Not Glial Glucose Transporter 1 Following Severe Diffuse Traumatic Brain Injury in Rats

Hamlin

Černak

Wixey

et al. 2001

Journal of Neurotrauma

View full text Add to dashboard Cite

Traumatic brain injury results in an increased brain energy demand that is associated with profound changes in brain glycolysis and energy metabolism. Increased glycolysis must be met by increasing glucose supply that, in brain, is primarily mediated by two members of the facilitative glucose transporter family, Glut1 and Glut3. Glut1 is expressed in endothelial cells of the blood-brain barrier (BBB) and also in glia, while Glut3 is the primary glucose transporter expressed in neurons. However, few studies have investigated the changes in glucose transporter expression following traumatic brain injury, and in particular, the neuronal and glial glucose transporter responses to injury. This study has therefore focussed on investigating the expression of the glial specific 45-kDa isoform of Glut1 and neuronal specific Glut3 following severe diffuse traumatic brain injury in rats. Following impact-acceleration injury, Glut3 expression was found to increase by at least 300% as early as 4 h after induction of injury and remained elevated for at least 48 h postinjury. The increase in Glut3 expression was clearly evident in both the cerebral cortex and cerebellum. In contrast, expression of the glial specific 45-kDa isoform of Glut1 did not significantly change in either the cerebral cortex or cerebellum following traumatic injury. We conclude that increased glucose uptake after traumatic brain injury is primarily accounted for by increased neuronal Glut 3 glucose transporter expression and that this increased expression after trauma is part of a neuronal stress response that may be involved in increasing neuronal glycolysis and associated energy metabolism to fuel repair processes.

show abstract

“…Studies with cultured capillary endothelial cells also showed that glucose deprivation enhanced GLUT1 gene expression, with maximum effect observed 24 h after glucose removal (40). There is also convincing in vivo and in vitro evidence that neuronal GLUT3 is upregulated when glucose availability is reduced (99, 219,264,418); for example, 3-day starvation in mice increased brain GLUT3 mRNA by twofold, and 2-day glucose deprivation increased that of primary neuronal cultures by fourfold (264). In line with these data, work with primary cultures of rat neurons showed that 24-h hypoxia rapidly increased neuronal GLUT1 and GLUT3 mRNA up to 40-and 5-fold, respectively, with similar changes in GLUT1 mRNA measured in glia (49).…”

Section: Glucose Transportmentioning

confidence: 99%

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

Obrenovitch¹

2008

Physiological Reviews

230

176

View full text Add to dashboard Cite

Ischemic tolerance describes the adaptive biological response of cells and organs that is initiated by preconditioning (i.e., exposure to stressor of mild severity) and the associated period during which their resistance to ischemia is markedly increased. This topic is attracting much attention because preconditioning-induced ischemic tolerance is an effective experimental probe to understand how the brain protects itself. This review is focused on the molecular and related functional changes that are associated with, and may contribute to, brain ischemic tolerance. When the tolerant brain is subjected to ischemia, the resulting insult severity (i.e., residual blood flow, disruption of cellular transmembrane gradients) appears to be the same as in the naive brain, but the ensuing lesion is substantially reduced. This suggests that the adaptive changes in the tolerant brain may be primarily directed against postischemic and delayed processes that contribute to ischemic damage, but adaptive changes that are beneficial during the subsequent test insult cannot be ruled out. It has become clear that multiple effectors contribute to ischemic tolerance, including: 1) activation of fundamental cellular defense mechanisms such as antioxidant systems, heat shock proteins, and cell death/survival determinants; 2) responses at tissue level, especially reduced inflammatory responsiveness; and 3) a shift of the neuronal excitatory/inhibitory balance toward inhibition. Accordingly, an improved knowledge of preconditioning/ischemic tolerance should help us to identify neuroprotective strategies that are similar in nature to combination therapy, hence potentially capable of suppressing the multiple, parallel pathophysiological events that cause ischemic brain damage.

show abstract

Changes of glucose transporters in the cerebral adaptation to hypoglycemia

Cited by 42 publications

References 25 publications

Changes in Regional Brain 18F-Fluorodeoxyglucose Uptake at Hypoglycemia in Type 1 Diabetic Men Associated With Hypoglycemia Unawareness and Counter-Regulatory Failure

Changes in Regional Brain 18F-Fluorodeoxyglucose Uptake at Hypoglycemia in Type 1 Diabetic Men Associated With Hypoglycemia Unawareness and Counter-Regulatory Failure

Increased Expression of Neuronal Glucose Transporter 3 but Not Glial Glucose Transporter 1 Following Severe Diffuse Traumatic Brain Injury in Rats

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

Contact Info

Product

Resources

About