Investigational agents that protect pancreatic islet beta-cells from failure.
Type 2 diabetes is associated with insulin resistance and reduced insulin secretion, which results in hyperglycaemia. This can then lead to diabetic complications such as retinopathy, neuropathy, nephropathy and cardiovascular disease. Although insulin resistance may be present earlier in the progression of the disease, it is now generally accepted that it is the deterioration in insulin-secretory function that leads to hyperglycaemia. This reduction in insulin secretion in Type 2 diabetes is due to both islet beta-cell dysfunction and death. Therefore, interventions that maintain the normal function and protect the pancreatic islet beta-cells from death are crucial in the treatment of Type 2 diabetes so that plasma glucose levels may be maintained within the normal range. Recently, a number of compounds have been shown to protect beta-cells from failure. This review examines the evidence that the existing therapies for Type 2 diabetes that were developed to lower plasma glucose (metformin) or improve insulin sensitivity (thiazolidinediones) may also have islet-protective function. Newer emerging therapeutic agents that are designed to increase the levels of glucagon-like peptide-1 not only stimulate insulin secretion but also appear to increase islet beta-cell mass. Evidence will also be presented that the future of drug therapy designed to prevent beta-cell failure should target the formation of advanced glycation end products and alleviate oxidative and endoplasmic reticulum stress.
Aston-Mourney
Kathryn
K
Department of Medicine (AH/NH), Heidelberg Repatriation Hospital, University of Melbourne, Heidelberg Heights, Victoria 3081, Australia.
Proietto
Joseph
J
Andrikopoulos
Sofianos
S
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism
D015507:Drugs, Investigational; D007004:Hypoglycemic Agents