Preservation of beta-cell function by targeting beta-cell mass.
Type 2 diabetes is characterized by progressive beta-cell dysfunction and a reduction in beta-cell mass. Pancreatic islets are a target for adverse effectors such as high concentrations of glucose, pro-inflammatory cytokines and increased free fatty acid concentrations - which are associated with adiposity, insulin resistance and the induction of beta-cell apoptosis. If the beta-cell mass is already below the threshold for maintaining normoglycemia, the expansion of beta-cell mass is the only option for achieving normoglycemia without the use of additional glucose-lowering agents. Therapies based on glucagon-like peptide-1 and combinations of growth factors such as epidermal growth factor and gastrin are promising new strategies for beta-cell preservation. In this review, we address the mechanisms involved in beta-cell dysfunction and beta-cell loss, and provide a rationale for pharmacological intervention for the preservation and/or expansion of beta-cell mass in type 2 diabetes.
de Koning
Eelco J P
EJ
Department of Nephrology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. e.dekoning@lumc.nl <e.dekoning@lumc.nl>
Bonner-Weir
Susan
S
Rabelink
Ton J
TJ
D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors; D019610:Cytoprotection; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009765:Obesity / Q000473:pathology; D018027:Receptors, Glucagon / Q000819:agonists; D012084:Renin-Angiotensin System / Q000187:drug effects
D016207:Cytokines; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D016328:NF-kappa B; D018027:Receptors, Glucagon