Highlights

Striking a balance

27 Apr 2010

Blood vessel development in the pancreas is regulated by the signaling molecule STAT3

Fig. 1: STAT3 (red) and insulin (green) expression in the pancreas of control mice (top) and STAT3-deficient mice (bottom). Glucose regulation and blood vessel development was abnormal in the STAT3-deficient mice (scale bar, 50 µm).

Fig. 1: STAT3 (red) and insulin (green) expression in the pancreas of control mice (top) and STAT3-deficient mice (bottom). Glucose regulation and blood vessel development was abnormal in the STAT3-deficient mice (scale bar, 50 µm).

Reproduced from Ref. 1 © 2010 The Endocrine Society

An inability to regulate blood glucose levels and vascular abnormalities of the pancreas have been found in mice lacking a signaling protein called ‘signal transducer and activator of transcription 3’ (STAT3). The work, completed by an international team of researchers led by Weiping Han from the Singapore Bioimaging Consortium of A*STAR, could have implications for the treatment of diabetes.

Blood vessels transport glucose to the pancreas. When the levels are too high, the pancreas releases the hormone insulin, which is then transported away by other pancreatic blood vessels. Pancreatic dysfunction is linked to diabetes—the inability to regulate blood glucose levels—which, if left untreated, can lead to kidney failure or cardiovascular complications.

Since STAT3 regulates blood vessel formation in pancreatic cancer, Han and co-workers generated mice lacking this signaling protein in the pancreas (Fig. 1). They found that mice lacking STAT3 could not clear glucose from their blood as quickly as their normal counterparts. The researchers also found that, although the glucose-sensing function of the pancreas functioned normally in STAT3-deficient mice, and the pancreas released sufficient insulin in tissue culture after glucose administration, the live mice released less insulin in response to an injection of glucose.

Suspicion as to the cause of defective insulin release and glucose control in the STAT3-deficient mice then fell to the conduit of insulin from the pancreas to the rest of the body—the blood vessels.

After labeling blood vessels in the pancreas with a marker called CD31, Han and his co-workers observed that the density of blood vessels in the pancreas was lower in STAT3-deficient mice than normal mice. They suggest that the cause is likely to be reduced expression of vascular endothelial growth factor-A (VEGF-A), a protein known to be involved in regulating blood vessel development in many different organ systems. “This study establishes that STAT3 signaling is important in the regulation of pancreas vascular development, possibly via its regulation of VEGF-A,” notes Han.

“We next plan to study whether vascular abnormalities in the pancreas are a common mechanism that leads to defective glucose regulation,” says Han. If blood vessel abnormalities do exist in the pancreas of individuals with diabetes, these findings suggest that targeting the vasculature of the pancreas—for example, by increasing blood vessel generation there—could be a novel therapeutic approach to treat diabetes.

The A*STAR-affiliated authors in this highlight are from the Singapore Bioimaging Consortium.

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References

Kostromina, E., Gustavasson, M., Wang, X., Lim, C.-Y., Radda, G.K., Li, C. & Han, W. Glucose intolerance and impaired insulin secretion in pancreas-specific STAT3 KO mice are associated with microvascular alterations in the pancreas. Endocrinology 151, 2050–2059 (2010). | article

This article was made for A*STAR Research by Nature Research Custom Media, part of Springer Nature