Editors' ChoiceMetabolism

Important Job for a Nervous Glucose Transporter

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Science Translational Medicine  15 Jan 2014:
Vol. 6, Issue 219, pp. 219ec13
DOI: 10.1126/scitranslmed.3008283

The endocrine pancreas is innervated by both the sympathetic and parasympathetic nervous systems, which play an important role in controlling insulin and glucagon secretion. However, it is not fully understood how glucose regulates the activity of the autonomic nervous system in the pancreatic islets and what the long-term effects of this activity are on β cell mass and function.

The glucose transporter 2 (Glut2), which is widely expressed in pancreatic β cells and in the liver, was previously demonstrated to be expressed also in various areas of the central and peripheral nervous systems. The exact role of Glut2 in the nervous system was not clear, although it has been suggested to participate in central glucose sensing and the control of feeding and glucose homeostasis. Recently, Tarussio et al. studied a mouse model with inactivation of Glut2 in the central and peripheral nervous systems. The absence of Glut2 in the nervous system resulted in decreased β cell proliferation in the postnatal period, which led to an ~30% reduction in β cell mass in adult mice. Although these mice had normal body weight and energy expenditure, they progressively developed β cell dysfunction and glucose intolerance, which were further accelerated by a high-fat diet. The authors demonstrated that the decrease in β cell mass resulted from decreased ability of glucose to stimulate the activity of the parasympathetic system. However, they could not yet identify what are the Glut2-expressing cells in the brain, or how Glut2 expression controls the parasympathetic outflow to the pancreas.

In addition to reduced β cell mass, exposure of these mice to high-fat diet resulted in impaired glucose-stimulated first-phase release of insulin and abnormally elevated secretion of glucagon. Because these abnormalities are characteristically observed in patients with type 2 diabetes, the suggested protective effects of parasympathetic activity on β cell mass and function may have an exciting translational potential for diabetes prevention in humans. In addition, it is also possible that postnatal exposure to environmental factors that may interfere with Glut2 expression or function in the brain might increase the risk for the development of glucose intolerance and diabetes later in life.

D. Tarussio et al., Nervous glucose sensing regulates postnatal β cell proliferation and glucose homeostasis. J. Clin. Invest. 124, 413–424 (2014). [Full Text]

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