Study finds small colony of neurons modulate amount of insulin the pancreas produces.


The brain is the key regulator of appetite, body weight and metabolism. Specifically, there is a small group of hypothalamus neurons, named the Proopiomelanocortin neurons (POMC), which can detect and integrate signals that inform on the energy state of the organism and activate the appropriate physiological responses. These neurons are sensitive to fluctuations in nutrients such as glucose, fatty acids and amino acids. However, the precise mechanisms underlying nutrient sensing in POMC neurons is poorly understood.  Now, a study led by researchers at IRB Barcelona identifies the connection between POMC neurons in the hypothalamus and the release of insulin by the pancreas, and describes new molecular mechanisms involved in this pathway. The team state that their study shows mitochondrial dynamics mediated by Mitofusin 1 in POMC neurons couple nutrient sensing with systemic glucose metabolism.  The study is published in the journal Cell Metabolism.

Previous studies show that POMC neurons can detect changes in nutrient availability, however, the molecular mechanisms involved are not known.  In the past the molecular mechanisms involved in POMC neuron’s ability to detect fluctuations in nutrients have been linked to changes in the shape of mitochondria.  This phenomenon is known as mitochondrial dynamics, a mechanism of energy adaptation in changing metabolic conditions to adjust the needs of cells.  To test this theory, the current study investigates whether defects in the mitochondrial dynamics of POMC neurons can cause alterations in metabolism.

The current study ablates the mitochondrial dynamics protein, Mitofusin 1, in the POMC cells of mice.  Results show that these mice have an altered detection of glucose levels and adaptation between the fasting state and being fed.  Data findings show that defects in mitochondrial dynamics lead to disturbances in glucose metabolism which are caused by a lower secretion of insulin.

Results show that POMC neurons are involved in the control of the intake and the amount of insulin secreted by the beta cells of the pancreas.  Data findings show that this communication between the hypothalamus and the pancreas depends on the activity of the protein Mitofusin 1.  The group explain the alterations are due to a disproportionate, though transitory, increase in the production of radical oxygen species in the hypothalamus; when the levels of  radical oxygen species in the hypothalamus are restored in the laboratory, the pancreas starts to secrete the correct levels of insulin again.

The team surmise that their data shows Mitofusin 1-mediated mitochondrial dynamics in POMC neurons are an intrinsic nutrient-sensing mechanism, and unveils a previously unknown link between this subset of neurons and insulin release.  For the future the researchers state that understanding the mechanisms involved in regulating insulin is important and helps to better understand the pathophysiology of diabetes.

Source: Institute for Research in Biomedicine (IRB Barcelona)

 

This is a fluorescence microscopy image of the hypothalamus arcuate nucleus with POMC neurons in green. Credit: Image: Alicia G Gómez-Valadés.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s