Diabetes Research

With an estimated 1.6 million deaths in 2015, diabetes has advanced to a leading health problem worldwide. Diabetes refers to a heterogeneous group of metabolic disorders associated with high blood sugar levels, which develop either when the pancreas does not produce enough insulin (type 1 diabetes), or the body cannot effectively use the supplied insulin (type 2 diabetes). Long-time hyperglycemia causes serious damage to many of the body’s systems, eventually resulting in heart attacks, strokes, blindness, kidney failure, or lower-limb amputation. Such adverse effects involve a complex pathology that includes many cellular and subcellular changes (Alam et al., 2014). Research is crucial, and in numerous studies, scientists are working to develop novel methods to both prevent and treat this pandemic.

One promising novel therapeutic approach involves the use of pluripotent stem cells (PSCs), as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Recent efforts focus on the potential of iPSCs to differentiate into insulin-secreting pancreatic β-cells, and on the use of patient-derived stem cells for drug screening (Abdelalim et al., 2014). New studies on the role of innate immunity in the development of type 2 diabetes have shown that increased numbers of immune cells, specifically macrophages, are associated with dysfunctions of pancreatic islets (Ehses et al., 2007). The increased use of bioreactors in regenerative medicine in the future will provide better in vitro cell culture systems, and allow a better understanding of the pathophysiology of both type 1 and type 2 diabetes (Minteer et al., 2014).

Insulin resistance is one major feature of diabetes type 2 and occurs when muscle, fat, and liver cells fail to properly respond to insulin, and they cannot easily absorb glucose from the bloodstream. Obesity is considered the major risk factor for insulin resistance, and recent research has focused on the role of adipose tissue as endocrine organ (Arcidiacono et al. 2017). Preadipocytes can be induced to differentiate into mature adipocytes, which offer a good in vitro model for the investigation of the mechanisms controlling obesity-induced insulin resistance. Novel assays have also evidenced the role of vascular endothelial cells dysfunctions in the development of metabolic diseases. Therefore, therapeutic approaches could focus on endothelial cell metabolism (Li et al., 2017). In addition, many studies have highlighted the links between chronic inflammation and insulin resistance, and the role that activated macrophages can play in type 2 diabetes. So, investigating macrophages could reveal new therapeutic strategies for metabolic diseases (Ahmed et al., 2017).

In diabetes, hyperglycemia-induced oxidative stress can lead to endothelial dysfunction, which contributes to the development of diabetes-associated complications, including retinopathy, nephropathy, neuropathy, ischemic heart disease, stroke, and peripheral vascular disease. Aberrant angiogenesis is one of the main reasons for these vascular complications. This is why the underlying cellular processes need to be better characterized, as multiple mechanisms are probably involved (Roberts and Porter, 2013).

Difficulty in wound healing is a common complication of diabetes mellitus, and is characterized by high rates of infection and amputation. Promising new treatments include the use of keratinocytes, fibroblasts, platelets, or mesenchymal stem cells, all of which have been shown to promote wound healing (You et al., 2012; You et al., 2014; Cobos et al., 2015; Han et al., 2015).

The diabetic environment negatively affects muscle progenitor cells, causing them to fail to maintain healthy muscle. This contributes to the progression of additional diabetic complications, as shown in several in vitro studies (D’souza et al, 2013).