Beta Cell Biology
The threat of obesity and diabetes
The incidence of obesity and diabetes has increased rapidly over the last decades in both developed and developing countries and post a major threat to the health of a large proportion of the population. Type 2 diabetes develops in association with obesity because the pancreatic beta cells fail to compensate for the increased demand for insulin as a result of obesity induced insulin resistance. Type 1 diabetes develops as a result of specific destruction of the pancreatic beta cells by an immune-mediated mechanism, but the cause of the increase in incidence is not known.
Beta cells' amazing ability
Stimulation of beta cell generation for the treatment of both Type 1 and Type 2 diabetes is attractive because it directly addresses the major functional deficiency underlying the disease. The ability of beta cells to undergo mitosis and serve as a source for new beta cells and thus beta cell regeneration has been shown to occur both in vivo and in vitro and can be stimulated by specific growth factors. Also the ability of the organism to generate new beta cells from stem or precursor cell populations has been proposed as a mechanism for the generation of beta cells in response to metabolic demand.
Studying beta cells
We use a number of in vitro and in vivo models systems to study the molecular and cellular basis for stimulation of beta cell growth and differentiation. Beta cells from animals or humans are cultured and the proliferation and function in response to various factors are investigated. The molecular mechanisms responsible for these effects are studied by analysis of intracellular signalling and gene expression studies. Specific pathways are analyzed by over-expression or knock-down of specific components of the regulatory pathways. In vivo, we use mouse and rat models of diabetes, pregnancy and obesity to study the hormones and cellular basis for up-regulation of beta cells mass. In particular the conditions in which beta cell up-regulation fails and diabetes develops are in focus. Pathways and factors identified as being involved in beta cells regulation during obesity, pregnancy and diabetes are being studied in transgenic and knock-out mouse models for their potential in preventing or curing diabetes.