MCT2 expression in the hypothalamus and the counterregulatory response to hypoglycemia

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Vincent Porcelli (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Joseph L. Beverly

Abstract: The human body seeks to maintain a stable physiological blood glucose concentration, despite a constantly changing availability of energy from eating. During food consumption, blood sugar would typically increase with time and during fasting, the opposite would be true. The body is able to release specific hormones to bring about either the storage or release of glucose from specific sites in the body. While this is all well and good, the body needs a sensor of sorts to determine when these actions need to take place. The brain, being the complex control center of the body, has such a site. The ventromedial hypothalamus is responsible for determining systemic glycemic levels. The exact mechanism that exists for the sensing isn’t fully understood, but it involves the VMH neurons. The loss of glucose, possibly due to fasting and a depleted amount of stored glucose, would lead to a response in the neurons that now lack fuel. While in a state of hypoglycemia, the neurons still need to function, and that is where the proposed astrocyte to neuron lactate shuttle hypothesis comes into play. This hypothesis suggests that glycogen stores in the astrocytes would be mobilized and converted to lactate, where it would be exported into the interstitial space and taken up via MCT2 proteins into the neurons to provide energy. In my study, we hypothesized that the knockdown of MCT2 proteins in the VMH will lead to an increased epinephrine response with recurrent bouts of exogenous-insulin induced hypoglycemia. Our results showed that MCT2 protein is very important to the function of energy sensing in the VMH and the loss of available lactate might simulate a bout of hypoglycemia.

Additional Information

Publication
Thesis
Language: English
Date: 2017
Keywords
Astrocyte to neuron lactate shuttle, Counter regulatory response, Diabetes, MCT2, Recurrent hypoglycemia
Subjects
Hypothalamus
Hypoglycemia
Blood sugar
Glycogen
Neurons
Proteins
Astrocytes
Lactate

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