Editors' ChoiceEndocrinology

PANDERing to the Liver in Glucose Control

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Science Translational Medicine  06 Oct 2010:
Vol. 2, Issue 52, pp. 52ec154
DOI: 10.1126/scitranslmed.3001751

Type 2 diabetes can be caused by several factors, the most important of which is abnormal regulation of glucose. Normally, glucose regulation is under the control of two hormones produced by the pancreas, insulin and glucagon. During fasting and in response to glucagon, the liver becomes an important player in glucose metabolism by producing glucose from noncarbohydrate sources (gluconeogenesis). The increase in glucose (hyperglycemia) during fasting is a risk factor for developing type 2 diabetes. A recent screen uncovered a new pancreatic-derived factor (PANDER) that is present in α and β pancreatic cells and also binds to receptors on liver cells (hepatocytes). This finding prompted Wilson et al. to examine whether PANDER has a role in glucose metabolism in the liver.

Wilson and colleagues used an adenovirus to overexpress PANDER in mouse liver. They discovered that under normal conditions, glucose levels remained stable, but during fasting they increased. The investigators then looked at the expression of gluconeogenesis genes in the livers of fasting mice overexpressing PANDER. They found increased expression of two key gluconeogenesis genes—PEPCK involved in glucose production and G6Pase involved in glucose release—in these mice as compared with that in control animals. Moving to cultured hepatocytes in vitro, they then demonstrated that PANDER acts directly on the transcription factor cAMP response element–binding protein (CREB) to up-regulate expression of these two gluconeogenesis genes.

This study illustrates the role of a recently discovered protein in promoting hyperglycemia during fasting in mice. Moreover, this work sheds light on new mechanisms controlling liver gluconeogenesis and pinpoints a potential new target for drug development in type 2 diabetes.

C. G. Wilson et al., Liver-specific overexpression of pancreatic-derived Factor (PANDER) induces fasting hyperglycemia in mice. Endocrinology 15 September 2010 (10.1210/en2010-0379). [Abstract]

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