Loss of pancreatic islet b-cell mass and b-cell dysfunction are central in the development of type 2 diabetes (T2DM). We recently showed that mature human insulincontaining b-cells can convert into glucagon-containing a-cells ex vivo. This loss of b-cell identity was characterized by the presence of b-cell transcription factors (Nkx6.1, Pdx1) in glucagon + cells. Here, we investigated whether the loss of b-cell identity also occurs in vivo, and whether it is related to the presence of (pre)diabetes in humans and nonhuman primates. We observed an eight times increased frequency of insulin + cells coexpressing glucagon in donors with diabetes. Up to 5% of the cells that were Nkx6.1 + but insulin 2 coexpressed glucagon, which represents a five times increased frequency compared with the control group. This increase in bihormonal and Nkx6.1 + glucagon + insulin 2 cells was also found in islets of diabetic macaques. The higher proportion of bihormonal cells and Nkx6.1 + glucagon + insulin 2 cells in macaques and humans with diabetes was correlated with the presence and extent of islet amyloidosis. These data indicate that the loss of b-cell identity occurs in T2DM and could contribute to the decrease of functional b-cell mass. Maintenance of b-cell identity is a potential novel strategy to preserve b-cell function in diabetes.Loss of pancreatic b-cell mass and b-cell dysfunction are central in the development of type 2 diabetes (T2DM) and, in combination with peripheral insulin resistance, lead to hyperglycemia (1). Whereas b-cells, on the one hand, fail to properly secrete insulin at a given glucose level, there is also a progressive decline in the number of b-cells (2,3). Loss of b-cell mass has been ascribed to increased apoptosis in T2DM (4). In patients with T2DM, b-cell mass can be up to 40-60% lower than in healthy control subjects (4-6). In addition, abnormal function of glucagon-producing a-cells leading to hyperglucagonemia is associated with T2DM (7). b-cell dedifferentiation and subsequent transition to other islet cell types were suggested as an alternative explanation for the loss of functional b-cell mass in mice (8,9). In this concept, b-cells lose insulin content and insulin secretory capacity followed by the production of other endocrine hormones such as glucagon (8). We recently showed (10) that loss of b-cell identity with the conversion of b-cells into glucagon-containing a-cells can occur in human pancreatic islets ex vivo.A number of transcription factors have been identified to be essential for the development and maintenance of functional b-cells (11,12). Recent reports (13,14) indicate that a selective loss of transcription factors MafA, Nkx6.1, and Pdx1 is associated with b-cell dysfunction and T2DM. Chronic hyperglycemia in rats is accompanied by the loss of b-cell transcription factors (15). Moreover, mouse b-cells that genetically lack FOXO1 can dedifferentiate in vivo under conditions of metabolic stress and subsequently can convert (or transdifferentiate) into glucagonproducing a-cells...

Scientists’ participation in science communication and public engagement activities is considered important and a duty. However, in particular, the science-media relationship has not been studied frequently. In this paper, we present findings from interviews with both scientists and journalists which were guided by the Theory of Planned Behavior. Results show that different behavioural, normative and control beliefs underlie scientists’ and journalists’ participation in science-media interactions. Both groups are positive about science-media interactions, but scientists perceive various disadvantages in this relationship while journalists perceive mainly practical barriers. Enhancing mutual understanding and further research is suggested.

Type 2 diabetes (T2DM) is associated with pancreatic islet dysfunction. Loss of β-cell identity has been implicated via dedifferentiation or conversion to other pancreatic endocrine cell types. How these transitions contribute to the onset and progression of T2DM is unknown. The aims of this study were to determine the degree of epithelial-to-mesenchymal transition occurring in α and β cells and to relate this to diabetes-associated (patho)physiological conditions. The proportion of islet cells expressing the mesenchymal marker vimentin was determined by immunohistochemistry and quantitative morphometry in specimens of pancreas from human donors with T2DM ( = 28) and without diabetes (ND, = 38) and in non-human primates at different stages of the diabetic syndrome: normoglycaemic (ND, = 4), obese, hyperinsulinaemic (HI, = 4) and hyperglycaemic (DM, = 8). Vimentin co-localised more frequently with glucagon (α-cells) than with insulin (β-cells) in the human ND group (1.43% total α-cells, 0.98% total β-cells, median; < 0.05); these proportions were higher in T2DM than ND (median 4.53% α-, 2.53% β-cells; < 0.05). Vimentin-positive β-cells were not apoptotic, had reduced expression of Nkx6.1 and Pdx1, and were not associated with islet amyloidosis or with bihormonal expression (insulin + glucagon). In non-human primates, vimentin-positive β-cell proportion was larger in the diabetic than the ND group (6.85 vs 0.50%, medians respectively, < 0.05), but was similar in ND and HI groups. In conclusion, islet cell expression of vimentin indicates a degree of plasticity and dedifferentiation with potential loss of cellular identity in diabetes. This could contribute to α- and β-cell dysfunction in T2DM.

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