The global prevalence of diabetes mellitus and its severe complications is on the rise. The study of the pathogenesis of the onset and the progression of complications related to the disease, as well as the search for new therapeutic agents and methods of treatment, remains relevant. Experimental models are extremely important in the study of diabetes. This survey contains a synthesis of the most commonly used experimental animal models described in scientific literature. The mechanisms of the streptozotocin model are also analyzed and discussed, as it is considered as the most adequate and easily reproducible diabetes model. A review of the significant advantages and disadvantages of the described models has also been conducted.
Great advances in type 1 diabetes (T1D) and type 2 diabetes (T2D) treatment have been made to this day. However, modern diabetes therapy based on insulin injections and cadaveric islets transplantation has many disadvantages. That is why researchers are developing new methods to regenerate the pancreatic hormone-producing cells in vitro. The most promising approach is the generation of stem cell-derived beta cells that could provide an unlimited source of insulin-secreting cells. Recent studies provide methods to produce beta-like cell clusters that display glucose-stimulated insulin secretion—one of the key characteristics of the beta cell. However, in comparison with native beta cells, stem cell-derived beta cells do not undergo full functional maturation. In this paper we review the development and current state of various protocols, consider advantages, and propose ways to improve them. We examine molecular pathways, epigenetic modifications, intracellular components, and the microenvironment as a possible leverage to promote beta cell functional maturation. A possibility to create islet organoids from stem cell-derived components, as well as their encapsulation and further transplantation, is also examined. We try to combine modern research on beta cells and their crosstalk to create a holistic overview of developing insulin-secreting systems.
Type 2 diabetes mellitus (T2DM) is the most common endocrine disorder (90%) in the world; it has numerous clinical, immunological, and genetic differences from type 1 diabetes mellitus. The pathogenesis of T2DM is complex and not fully clear. To date, animal models remain the main tool by which to study the pathophysiology and therapy of T2DM. Rodents are considered the best choice among animal models, because they are characterized by a small size, short induction period, easy diabetes induction, and economic efficiency. This review summarizes data on experimental models of T2DM that are currently used, evaluates their advantages and disadvantages vis-a-vis research, and describes in detail the factors that should be taken into account when using these models. Selection of a suitable model for tackling a particular issue is not always trivial; it affects study results and their interpretation.
Diabetes affects over 350 million people worldwide, with the figure projected to rise to nearly 500 million over the next 20 years, according to the World Health Organization. Insulin-dependent diabetes mellitus (type 1 diabetes) is an endocrine disorder caused by an autoimmune reaction that destroys insulin-producing -cells in the pancreas, which leads to insulin deficiency. Administration of exogenous insulin remains at the moment the treatment mainstay. This approach helps to regulate blood glucose levels and significantly increases the life expectancy of patients. However, type 1 diabetes is accompanied by long-term complications associated with the systemic nature of the disease and metabolic abnormalities having a profound impact on health. Of greater impact would be a therapeutic approach which would overcome these limitations by better control of blood glucose levels and prevention of acute and chronic complications. The current efforts in the field of regenerative medicine are aimed at finding such an approach. In this review, we discuss the time-honored technique of donor islets of Langerhans transplantation. We also focus on the use of pluripotent stem and committed cells and cellular reprogramming. The molecular mechanisms of pancreatic differentiation are highlighted. Much attention is devoted to the methods of grafts delivery and to the materials used during its creation.
Mouse submandibular salivary gland cells and liver progenitor cells from long-term in vitro cultures with a high proliferation potential were side-by-side compared by methods of immunocytochemistry, quantitative real-time PCR, flow cytometry, and transcriptome analysis. The two cell types were found to be similar in expressing cell markers such as EpCAM, CD29, c-Kit, Sca-1, and c-Met. In addition, both cell types expressed cytokeratins 8, 18, and 19, alpha-fetoprotein, and (weakly) albumin. Unlike the liver cells, however, the salivary gland cells in culture showed high-level expression of cytokeratin 14 and CD49f, which was indicative of their origin from salivary gland ducts. Quantitative real-time PCR and deep-sequencing transcriptome analysis revealed similarities in the expression pattern of transcription factors between the two cell types. In this respect, however, the cultured salivary gland cells proved to be closer to exocrine cells of the pancreas than to the liver progenitor cells. Thus, ductal cells of postnatal submandibular salivary glands in culture show phenotypic convergence with progenitor cells of endodermal origin, suggesting that these glands may serve as a potential cell source for cellular therapy of hepatic and pancreatic disorders. The results of this study provide a deeper insight into the molecular features of salivary gland cells and may help optimize procedures for stimulating their differentiation in a specified direction.