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14-07-2016 | Diabetes | News | Article

Studies expand beta-cell knowledge

medwireNews: Two studies reveal four distinct subtypes of β cells and a marker that can distinguish proliferative from mature cells.

Furthermore, the first study, published in Nature Communications, shows that the distribution of the four β-cell subtypes varies in patients with Type 2 diabetes.

The four subtypes were categorised according to whether or not they expressed the tetraspanin CD9 and ST8SIA1 – an alpha-N-acetylneuraminide alpha-2,8-sialyltransferase, the function of which is unknown in endocrine cells.

A “sizeable list” of genes was differentially expressed between the subtypes, report Craig Dorrell (Oregon Health and Science University, Portland, USA) and co-researchers. The functions of most of these are not known, they say, but some, such as GLUT2, have an established role in insulin secretion, while others, such as G6PC2, are reportedly abnormally expressed in patients with Type 2 diabetes.

The islet cells were obtained from people who died and consented to organ donation. The distribution of β cell subtypes was consistent in 17 people who did not have diabetes at death, and did not differ between lean and obese people.

However, the distribution was significantly altered in patients with Type 2 diabetes and was highly variable between patients. For example, six of eight patients had “unusually high” proportions of ST8SIA1-expressing cells, whereas in the seventh they had disappeared and the eighth had a high proportion of CD9-expressing cells.

“The clearly abnormal distribution of β cell subsets in the majority of our small [Type 2 diabetes] sample set raises the possibility that the subtypes differ in their susceptibility to metabolic stress, proliferative capacity or differentiation state”, say Dorrell et al.

The second report – a research letter in Nature – shows that expression of Fltp, a gene from the signalling pathway that regulates the orientation of cells and organelles within body tissue, increases in the β cells of mice between postnatal days 1 and 11, as their cells mature.

Cells with high Fltp expression also had altered expression of 996 other genes, with increased expression of many with a known role in mature β-cell function. But levels of the proliferation marker Ki-67 were significantly lower in cells with Fltp expression than in those without, all indicating that Fltp expression identifies mature β cells, as opposed to proliferative cells.

“The availability of a unique marker for mature β-cells opens new ways to explore pathways regulating islet heterogeneity and might allow researchers to target β-cell maturation for cell-replacement and regenerative therapy”, say Heiko Lickert (Helmholtz Zentrum München, Germany) and study co-authors.

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016

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