A large body of data gathered over the last decades has identified the neuronal pathways which link the central nervous system with the autonomic innervation of the endocrine pancreas. These are important regulatory functions that are certainly keys for preserving the capacity of the endocrine pancreas to control glucose homeostasis over a lifetime and are implicated in diabetes.

It is known that the ventromedial nucleus of the hypothalamus (VMH) plays a critical role in regulating systemic glucose homeostasis. However, it is unclear how neurons in this brain area adapt to the changing metabolic environment to regulate circulating glucose levels.  Now, a study from researchers at Yale shows the spike in blood sugar levels that can come after a meal is controlled by the brain’s neuronal mitochondria, the powerhouse of cells.  The team state that the findings could provide a better understanding of how type 2 diabetes develops.  The opensource study is published in the journal Cell.

Previous studies show that glucose-sensing neurons of the VMH are either activated or inhibited by increased glucose levels, with their responses to changes in glucose levels shown to be important for the counter-regulatory responses following insulin-induced hypoglycemia and for the secretion of pancreatic insulin in response to increased glucose levels.  Alteration in mitochondrial dynamics has been observed in metabolic tissues of human and rodent models of diabetes. However, whether mitochondrial dynamics in neuronal populations of the VMH is involved in control of systemic glucose homeostasis is still ill-defined.  The current study defines a crucial role for mitochondria in a small subset of neurons of the VMH in systemic glucose control.

The current study investigated how neurons in the brain adapt to the glucose rush.  Results show that mitochondria of neurons feel the change in circulating glucose levels and that adaptive changes in these same mitochondria are at the core of the body’s ability to handle sugar in the blood.

To test this point, the lab generated several mouse models in which a specific mitochondrial protein called uncoupling protein 2 (UCP2) was either missing or present in varying amounts in the subset of brain cells that sense circulating sugar levels.  Data findings show that when sugar increases in the body, mitochondria in subsets of brain neurons rapidly change their shape and their function is altered.

The team surmise that their findings imply that alterations in this mechanism may be crucial for the development of metabolic diseases such as type 2 diabetes, where the body is not able to clear the blood from high levels of sugar that occur after meals.  For the future, the researchers plan on assessing whether alteration of this mitochondrial mechanism in the brain is involved in the development and propagation of type 2 diabetes.

Source: Yale School of Medicine