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

Hamlin, Gary P.; Černak, Ibolja; Wixey, Julie A.; Vink, Robert

doi:10.1089/08977150152693700

Cited by 59 publications

(45 citation statements)

References 37 publications

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“…It is also possible that TBI induces rapid alteration in MCT1 expression or alters MCT1 kinetics. Injury-induced alterations in glucose transporter expression have been reported as early at 4 h after TBI (Hamlin et al 2001) demonstrating the brain's potential to rapidly alter transporter numbers. The MCT1 has been shown to be pH sensitive and injury-induced pH changes could stimulate transport (Halestrap and Price 1999).…”

Section: Discussionmentioning

confidence: 99%

Increased cerebral uptake and oxidation of exogenous βHB improves ATP following traumatic brain injury in adult rats

Prins

Lee

Fujima

et al. 2004

Journal of Neurochemistry

101

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There is growing evidence of the brain's ability to increase its reliance on alternative metabolic substrates under conditions of energy stress such as starvation, hypoxia and ischemia. We hypothesized that following traumatic brain injury (TBI), which results in immediate changes in energy metabolism, the adult brain increases uptake and oxidation of the alternative substrate b-hydroxybutyrate (bHB). Arterio-venous differences were used to determine global cerebral uptake of bHB and production of 14 CO 2 from [ 14 C]3-bHB 3 h after controlled cortical impact (CCI) injury. Quantitative bioluminescence was used to assess regional changes in ATP concentration. As expected, adult sham and CCI animals with only endogenously available bHB showed no significant increase in cerebral uptake of bHB or 14 CO 2 production. Increasing arterial bHB concentrations 2.9-fold with 3 h of bHB infusion failed to increase cerebral uptake of bHB or 14 CO 2 production in adult sham animals. Only CCI animals that received a 3-h bHB infusion showed an 8.5-fold increase in cerebral uptake of bHB and greater than 10.7-fold increase in 14 CO 2 production relative to sham bHB-infused animals. The TBI-induced 20% decrease in ipsilateral cortical ATP concentration was alleviated by 3 h of bHB infusion beginning immediately after CCI injury. Keywords: alternative substrates, b-hydroxybutyrate, metabolism, traumatic brain injury. Although glucose remains the primary cerebral metabolic substrate under normal conditions, there are many physiological states during which the brain's reliance on glucose shifts to alternative substrates (Owen et al. 1967;Hawkins et al. 1971;Dahlquist and Persson 1976;Kries and Ross 1992;Vannucci and Vannucci 2000). In vitro studies have documented uptake and oxidation of 14 C-labeled glycerol (McKenna et al. 1986a) (Edmond et al. 1987). However, ketone bodies such as bHB are the only endogenously circulating alternative substrates that have been shown significantly to supplement cerebral metabolism (Owen et al. 1967;Hawkins et al. 1971;Dahlquist and Persson 1976). In normally fed adult mammals bHB metabolism comprises less than 3% of total cerebral metabolism and bHB is present in low circulating concentrations (0.1 mM) with negligible uptake into the brain (Hawkins et al. 1971). However, upon increasing bHB arterial concentrations by starvation for 2 days or more, cerebral uptake is significantly enhanced (Hawkins et al. 1971). Increased cerebral uptake of bHB has also been shown during development (Hawkins et al. 1971;Dahlquist and Persson 1976), following starvation (Owen et al. 1967) and in diabetes (Kries and Ross 1992). The brain's ability to increase its reliance on bHB appears to be a common form of cerebral metabolic adaptation under conditions of insufficient glucose availability and developmental increases in cerebral energy demand.The evidence for the use of bHB by the brain under conditions of cerebral metabolic stress suggests a role for this alternative substrate in cerebral metabolism after ...

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Section: Discussionmentioning

confidence: 99%

Increased cerebral uptake and oxidation of exogenous βHB improves ATP following traumatic brain injury in adult rats

Prins

Lee

Fujima

et al. 2004

Journal of Neurochemistry

101

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“…However, the patterns of GLUT1 and GLUT3 expression in mammals differ, with GLUT3 much more restricted in its distribution than GLUT1. 3,55 Within the preimplantation embryo, particularly the blastocyst, the patterns of GLUT1 and GLUT3 expression are substantially different, 56,57 as described below. One important functional difference between them is that GLUT3 may transport glucose at a higher rate than GLUT1, 58,59 potentially seven times faster, and therefore may be better suited to transport maternal glucose into the preimplantation embryo that encounters a low-glucose (1 mmol/L) environment.…”

Section: Discussionmentioning

confidence: 99%

Implications of Glucose Transporter Protein Type 1 (GLUT1)-Haplodeficiency in Embryonic Stem Cells for Their Survival in Response to Hypoxic Stress

Heilig

Brosius

Siu

et al. 2003

The American Journal of Pathology

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Glucose transporter protein type 1 (GLUT1) is a major glucose transporter of the fertilized egg and preimplantation embryo. Haploinsufficiency for GLUT1 causes the GLUT1 deficiency syndrome in humans, however the embryo appears unaffected. Therefore, here we produced heterozygous GLUT1 knockout murine embryonic stem cells (GT1؉/؊) to study the role of GLUT1 deficiency in their growth, glucose metabolism, and survival in response to hypoxic stress. GT1(؊/؊) cells were determined to be nonviable. Both the GLUT1 and GLUT3 high-affinity, facilitative glucose transporters were expressed in GT1(؉/؉) and GT1(؉/؊) embryonic stem cells. GT1(؉/؊) demonstrated 49 ؎ 4% reduction of GLUT1 mRNA. This induced a posttranscriptional, GLUT1 compensatory response resulting in 24 ؎ 4% reduction of GLUT1 protein. GLUT3 was unchanged. GLUT8 and GLUT12 were also expressed and unchanged in GT1(؉/؊). Stimulation of glycolysis by azide inhibition of oxidative phosphorylation was impaired by 44% in GT1(؉/؊), with impaired up-regulation of GLUT1 protein. Hypoxia for up to 4 hours led to 201% more apoptosis in GT1(؉/؊) than in GT1(؉/؉) controls. Caspase-3 activity was 76% higher in GT1(؉/؊) versus GT1(؉/؉) at 2 hours. Heterozygous knockout of GLUT1 led to a partial GLUT1 compensatory response protecting nonstressed cells. However, inhibition of oxidative phosphorylation and hypoxia both exposed their increased susceptibility to these stresses.

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“…Although glucose receptor/transporter was not estimated in the present study, the increased glycolysis must be met by increasing glucose supply that is primarily mediated by two members of the facilitative glucose transporter family [30]. Therefore, there is a possibility that fenugreek seed extract may bring about some of its effects through increasing the expression of glucose transporter especially GLUT4 as previously reported [31].…”

Section: Discussionmentioning

confidence: 52%

Regulation of hepatic and mucosal 6-phosphofructo-1-kinase activity by trigonella foenum-graecum linn (fenugreek) seeds of streptozotocin-induced diabetic rats

Ali¹,

Zamzami²,

Khoja³

2013

J Diab Res Clin Met

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Background: Trigonella foenum-graecum Linn. (fenugreek) can ameliorate hyperglycemia and dyslipidemia, however, the detailed mechanism is unclear. The present study aims to investigate the effect of fenugreek seeds water extract (FSE) on 6-phosphofructo-1-kinase (PFK-1) activity, a key enzyme of glycolysis, in the liver and small intestine of streptozotocin induced diabetic rats and its impact on plasma glucose and lipid concentrations. Methods: 50 male Wistar rats were used in this study. The rats were divided into five groups with 10 rats in each group: normal control rats (Group1), streptozotocin-induced diabetic rats (Group2), streptozotocin-induced diabetic rats + Fenugreek seeds (0.5g/500 ml water) (Group3), streptozotocin-induced diabetic rats + Fenugreek seeds (1.0g/500 ml water) (Group4), streptozotocin-induced diabetic rats + insulin (Group5). Blood samples were then collected after the period of treatment for the analysis of glucose, total cholesterol, triacylglycerol and insulin concentration. PFK-1 for liver and intestinal mucosa was extracted and assayed. Results: Diabetic rats showed significantly lower liver and intestinal mucosa PFK-1 activities (both at P<0.05) compared with control rats. Diabetic rats treated with FSE (1.0g / 500 ml water) showed a significant (P<0.0001) increase in the PFK-1 activity of liver and intestinal mucosa by 54% and 75% respectively. The plasma glucose concentrations of diabetic rats treated with 0.5g and 1.0g fenugreek / 500 ml water were significantly (P<0.001) decreased by 32% and 43%. In addition the concentrations of plasma total cholesterol and triacylglycerol were significantly (both at P<0.0001) decreased by 57% and 42%, respectively in rats treated with 1.0g fenugreek / 500 ml water, compared with non-treated diabetic rats. Conclusions: These results may suggest that the in-vivo hypoglycaemic effect of FSE is mediated, at least in part, by the activation of PFK-1 in intestinal and liver cells.

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

Cited by 59 publications

References 37 publications

Increased cerebral uptake and oxidation of exogenous βHB improves ATP following traumatic brain injury in adult rats

Increased cerebral uptake and oxidation of exogenous βHB improves ATP following traumatic brain injury in adult rats

Implications of Glucose Transporter Protein Type 1 (GLUT1)-Haplodeficiency in Embryonic Stem Cells for Their Survival in Response to Hypoxic Stress

Regulation of hepatic and mucosal 6-phosphofructo-1-kinase activity by trigonella foenum-graecum linn (fenugreek) seeds of streptozotocin-induced diabetic rats

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