The recent discovery that genetically modified α cells can regenerate and convert into β-like cells in vivo holds great promise for diabetes research. However, to eventually translate these findings to human, it is crucial to discover compounds with similar activities. Herein, we report the identification of GABA as an inducer of α-to-β-like cell conversion in vivo. This conversion induces α cell replacement mechanisms through the mobilization of duct-lining precursor cells that adopt an α cell identity prior to being converted into β-like cells, solely upon sustained GABA exposure. Importantly, these neo-generated β-like cells are functional and can repeatedly reverse chemically induced diabetes in vivo. Similarly, the treatment of transplanted human islets with GABA results in a loss of α cells and a concomitant increase in β-like cell counts, suggestive of α-to-β-like cell conversion processes also in humans. This newly discovered GABA-induced α cell-mediated β-like cell neogenesis could therefore represent an unprecedented hope toward improved therapies for diabetes.

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Diabetes can result from the loss or dysfunction of insulin-producing δ cells. Druelle et al. find that ectopic expression of the pancreatic beta cell master gene Pax4 in somatostatin-expressing δ cells triggers an endocrine cell neogenesis process. Importantly, the beta-like cells thereby generated are functional and can partly reverse the consequences of chemically induced diabetes.

).To efficiently treat type 1 diabetes, exogenous insulin injections currently represent the main approach to counter chronic hyperglycaemia. Unfortunately, such a therapeutic approach does not allow for perfectly maintained glucose homeostasis and, in time, cardiovascular complications may arise. Therefore, seeking alternative/improved treatments has become a major health concern as an increasing proportion of type 2 diabetes patients also require insulin supplementation. Towards this goal, numerous laboratories have focused their research on β-cell replacement therapies. Herein, we will review the current state of this research area and describe the cell sources that could potentially be used to replenish the depleted β-cell mass in diabetic patients.

Ghrelin is a gastric peptide with anabolic functions. It acutely stimulates growth hormone (GH) secretion from the anterior pituitary glands and modulates hypothalamic circuits that control food intake and energy expenditure. Besides its central activity, ghrelin is also involved in the regulation of pancreatic development and physiology. Particularly, several studies highlighted the ability of ghrelin to sustain β-cell viability and proliferation. Furthermore, ghrelin seems to exert inhibitory effects on pancreatic acinar and endocrine secretory functions. Due to its pleiotropic activity on energy metabolism, ghrelin has become a topic of great interest for experimental research focused on type II diabetes and obesity. The aim of this review is to illustrate the complex and not fully understood interplay between ghrelin, pancreas and glucose homeostasis.

Both type 1 and type 2 diabetes are conditions that are associated with the loss of insulin-producing β-cells within the pancreas. An active research therefore aims at regenerating these β-cells with the hope that they could restore euglycemia. The approaches classically used consist in mimicking embryonic development, making use of diverse cell sources or converting pre-existing pancreatic cells. Despite impressive progresses and promising successes, it appears that we still need to gain further insight into the molecular mechanisms underlying β-cell development. This becomes even more obvious with the emergence of a relatively new field of research, epigenetics. The current review therefore focuses on the latest advances in this field in the context of β-cell (neo-)genesis research.

Type 1 diabetes is an auto-immune disease resulting in the loss of pancreatic β-cells and, consequently, in chronic hyperglycemia. Insulin supplementation allows diabetic patients to control their glycaemia quite efficiently, but treated patients still display an overall shortened life expectancy and an altered quality of life as compared to their healthy counterparts. In this context and due to the ever increasing number of diabetics, establishing alternative therapies has become a crucial research goal. Most current efforts therefore aim at generating fully functional insulin-secreting β-like cells using multiple approaches. In this review, we screened the literature published since 2011 and inventoried the selected markers used to characterize insulin-secreting cells generated by in vitro differentiation of stem/precursor cells or by means of in vivo transdifferentiation. By listing these features, we noted important discrepancies when comparing the different approaches for the initial characterization of insulin-producing cells as true β-cells. Considering the recent advances achieved in this field of research, the necessity to establish strict guidelines has become a subject of crucial importance, especially should one contemplate the next step, which is the transplantation of in vitro or ex vivo generated insulin-secreting cells in type 1 diabetic patients.

The pancreas is an abdominal gland that serves 2 vital purposes: assist food processing by secreting digestive enzymes and regulate blood glucose levels by releasing endocrine hormones. During embryonic development, this gland originates from epithelial buds located on opposite sites of the foregut endoderm. Pancreatic cell specification and maturation are coordinated by a complex interplay of extrinsic and intrinsic signaling events. In the recent years, the canonical Wnt/β-catenin pathway has emerged as an important player of pancreas organogenesis, regulating pancreatic epithelium specification, compartmentalization and expansion. Importantly, it has been suggested to regulate proliferation, survival and function of adult pancreatic cells, including insulin-secreting β-cells. This review summarizes recent work on the role of Wnt/β-catenin signaling in pancreas biology from early development to adulthood, emphasizing on its relevance for the development of new therapies for pancreatic diseases.