Pancreatic β-Cell Mass as a Pharmacologic Target in Diabetes.
While the prevalence of maternal While the prevalence of diabetes mellitus reaches epidemic proportions, most available treatments still focus on the symptoms of the disease, rather than the underlying pathology. Types 1 and 2 diabetes have in common a deficit in β-cell mass. In type 1 diabetes, auto-immune β-cell destruction leads to an absolute deficit in β-cells, while in type 2 diabetes, insulin resistance and β-cell dysfunction cause a functional deficit. More recently, however, it has been suggested that type 2 diabetes is also marked by an absolute deficit in β-cell mass, although a causal relationship has not yet been established. Overall β-cell mass reflects the balance between the dynamic processes of β-cell expansion, through proliferation and neogenesis, and β-cell loss via apoptosis. Given that β-cell mass can be modified significantly by altering the rate of any of these mechanisms, therapies that modulate β-cell expansion and loss have garnered recent interest. We review herein the current therapeutics under investigation as modulators of β-cell mass dynamics, and the basic research that supports these novel therapeutic targets.
Stephen
S
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