School of Medicine and Health Sciences Poster Presentations

Title

A Developmental Profile of Glucose Transport and Utilization in the Brains of Mice

Document Type

Poster

Abstract Category

Neuroscience

Keywords

glucose, development, metabolism, neuroscience, GLUT

Publication Date

Spring 5-1-2019

Abstract

The brain is known to use glucose and related substrates for energy, as opposed to fatty acids and amino acids. How the brain specifically transports and uses glucose during development, however, has not been completely characterized. The aim of this project is to compile an age-specific, region-specific, and cell-specific profile of glucose transport and utilization during development using a mouse model. This profile, once completed, can be used to better understand changes to metabolism in pediatric disease states such as perinatal hypoxia, epilepsy, hyperglycemia, and mitochondrial disease. Mouse brains were harvested at ages P11, P15, and P30, which correspond to neonates, young children, and adolescents respectively. Dissected brains were probed by Western Blot for glucose transporters GLUT1, GLUT2, GLUT3, GLUT4, and GLUT8. We expected to see a shift in glucose metabolism between the ages of P15 and P30 based on an observed behavioral shift (increased activity and self-directed search for food). Results showed a significant increase in GLUT2, a transporter localized to astrocytes, and GLUT8, an insulin-dependent transporter. GLUT3, which is said to be neuron-specific, did not show any significant changes in expression over time. GLUT2 expression was significantly increased by P30 in the frontal cortex and the hippocampus but showed no significant difference in white matter. The increase in expression of GLUT2 makes sense as the proportion of astrocytes increases greatly during development. In the hippocampus. the astrocyte-neuronal lactate shuttle is implicated in the development of long-term memory; therefore, glucose uptake must be positively regulated here in order to provide enough substrate for the shuttle. The large increase in GLUT8 expression can be explained by the feeding pattern of mice during development. From birth to P15, the mice are still in their suckling phase, receiving mostly proteins and fatty acids through their mothers’ milk. These are broken down into ketones that are used as energy for the brain. By P30, however, the mice are feeding on their own and consume a diet significantly higher in carbohydrates, likely causing greater insulin release. Since GLUT8 is an insulin-dependent glucose transporter, this increase in insulin should cause an increase in expression of GLUT8. Although insulin-dependent GLUT4 should have shown similar patterns in expression, it is only weakly expressed in the brain and more prevalent in other peripheral tissues. Therefore, GLUT8 may be the key insulin-dependent glucose transporter in the brain. GLUT8 activity in diabetic patients, therefore, should be further explored.

Open Access

1

Comments

Presented at Research Days 2019.

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A Developmental Profile of Glucose Transport and Utilization in the Brains of Mice

The brain is known to use glucose and related substrates for energy, as opposed to fatty acids and amino acids. How the brain specifically transports and uses glucose during development, however, has not been completely characterized. The aim of this project is to compile an age-specific, region-specific, and cell-specific profile of glucose transport and utilization during development using a mouse model. This profile, once completed, can be used to better understand changes to metabolism in pediatric disease states such as perinatal hypoxia, epilepsy, hyperglycemia, and mitochondrial disease. Mouse brains were harvested at ages P11, P15, and P30, which correspond to neonates, young children, and adolescents respectively. Dissected brains were probed by Western Blot for glucose transporters GLUT1, GLUT2, GLUT3, GLUT4, and GLUT8. We expected to see a shift in glucose metabolism between the ages of P15 and P30 based on an observed behavioral shift (increased activity and self-directed search for food). Results showed a significant increase in GLUT2, a transporter localized to astrocytes, and GLUT8, an insulin-dependent transporter. GLUT3, which is said to be neuron-specific, did not show any significant changes in expression over time. GLUT2 expression was significantly increased by P30 in the frontal cortex and the hippocampus but showed no significant difference in white matter. The increase in expression of GLUT2 makes sense as the proportion of astrocytes increases greatly during development. In the hippocampus. the astrocyte-neuronal lactate shuttle is implicated in the development of long-term memory; therefore, glucose uptake must be positively regulated here in order to provide enough substrate for the shuttle. The large increase in GLUT8 expression can be explained by the feeding pattern of mice during development. From birth to P15, the mice are still in their suckling phase, receiving mostly proteins and fatty acids through their mothers’ milk. These are broken down into ketones that are used as energy for the brain. By P30, however, the mice are feeding on their own and consume a diet significantly higher in carbohydrates, likely causing greater insulin release. Since GLUT8 is an insulin-dependent glucose transporter, this increase in insulin should cause an increase in expression of GLUT8. Although insulin-dependent GLUT4 should have shown similar patterns in expression, it is only weakly expressed in the brain and more prevalent in other peripheral tissues. Therefore, GLUT8 may be the key insulin-dependent glucose transporter in the brain. GLUT8 activity in diabetic patients, therefore, should be further explored.