Chronic insulin hypoglycemia induces GLUT-3 protein in rat brain neurons

Abstract

Near-normalization of glycemia reduces the risks of chronic diabetic complications but increases the risk of serious hypoglycemia. Hypoglycemia can impair neuronal function in the brain and diminish awareness of subsequent hypoglycemic episodes, yet little is known about how neurons adapt to hypoglycemia. This study tests the hypothesis that isoform-specific alterations in brain glucose transport proteins occur in response to chronic hypoglycemia. To study this, groups of rats were injected with approximately 25 U/kg ultralente insulin daily at 1700 for 8 days to maintain hypoglycemia. Vascular-free and microvessel membrane fractions from brain were prepared for immunoblot analysis of GLUT-1 and GLUT-3 by use of isoform-specific antisera. Insulin treatment reduced blood glucose levels from 4.0 +/- 0.1 (vehicle-injected controls) to 1.7 +/- 0.1 mmol/l on day 8 (P < 0.001) and increased GLUT-3 protein expression (175.6% of control; P < 0.05). Microvascular GLUT-1 (55 kDa) tended to increase (195.6% of controls; P = 0.08) variably, whereas nonvascular GLUT-1 (45 kDa) was unchanged. We conclude that neuronal glucose transport protein (GLUT-3) expression adapts to chronic hypoglycemia. This adaptation may spare neuronal energy metabolism but could dampen neuronal signaling of glucose deprivation.

Effects of Peroxisome Proliferator-Activated Receptor Gamma Agonists on Brain Glucose and Glutamate Transporters after Stress in Rats

“…Taking into account the high affinity and dependence of neurons for glucose, it has been postulated that the activity of this transporter would play a beneficial role during glucose deprivation, hypoxic episodes or other metabolic compromising situations (Burant and Bell, 1992;Gerhart et al, 1992;Fattoretti et al, 2001;Burkhalter et al, 2003). Thus, GLUT-3 activity affords neuroprotection (Hara et al, 1989;Lee and Bondy, 1993;Urabe et al, 1996;Uehara et al, 1997), and its malfunctioning is related with neuronal damage (reviewed in McEwen and Reagan (2004)). We have shown that after repeated stress, at the stress intensity and duration evaluated in this article, the neuronal transporter GLUT-3 membrane expression results clearly affected supporting the preventive effects demonstrated of the PPARg agonists used in this particular experimental setting (García-Bueno et al, 2005a, b).…”

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

“…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).…”

Hipoglicemia recurrente como causa reversible de síndrome demencial en adultos mayores diabéticos, a propósito de un caso

“…Se ha evidenciado en modelos animales que la hipoglicemia prolongada induciría un aumento del transporte de glucosa a través de la barrera hemato-encefálica (BHE) por medio de un fenó-meno de up regulation de la expresión de GLUT 1 en la superficie luminal de la BHE y de GLUT 3 en las neuronas [10][11][12][13] .…”