Lisa Juntti-Berggren1, Per-Olof Berggren. 1. The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1:03, SE-171 76 Stockholm, Sweden.
Abstract
PURPOSE OF REVIEW: Type-1 and type-2 diabetes are diseases with an increasing number of patients and a complex, multifactorial pathogenesis. Apolipoprotein (apo) CIII is increased in both types of diabetes and interventions preventing the increase have effects on the development of diabetes. RECENT FINDINGS: ApoCIII affects intracellular Ca-handling by activating voltage-gated Ca-channels. ApoCIII is produced within the pancreatic islets and it increases in parallel with the development of insulin resistance and type-2 diabetes. Preventing the increase maintains a normal glucose tolerance as well as Ca-handling and no signs of inflammation can be seen in islets wherein the augmented local production of the apolipoprotein is absent. SUMMARY: ApoCIII has been found to interfere with both function and survival of the β-cell and thereby promote the development of diabetes. Increased levels of this apolipoprotein affects intracellular Ca-handling and insulin sensitivity, which finally results in impaired glucose homeostasis and diabetes. Interestingly, in a type-1 diabetes rat model lowering of apoCIII delays onset of diabetes. In type-2 diabetes insulin resistance within the pancreatic islets leads to a local increase in apoCIII that promotes inflammation and β-cell dysfunction. Hence, targeting apoCIII may constitute a novel pharmacological strategy to treat both type-1 and type-2 diabetes.
PURPOSE OF REVIEW: Type-1 and type-2 diabetes are diseases with an increasing number of patients and a complex, multifactorial pathogenesis. Apolipoprotein (apo) CIII is increased in both types of diabetes and interventions preventing the increase have effects on the development of diabetes. RECENT FINDINGS:ApoCIII affects intracellular Ca-handling by activating voltage-gated Ca-channels. ApoCIII is produced within the pancreatic islets and it increases in parallel with the development of insulin resistance and type-2 diabetes. Preventing the increase maintains a normal glucose tolerance as well as Ca-handling and no signs of inflammation can be seen in islets wherein the augmented local production of the apolipoprotein is absent. SUMMARY:ApoCIII has been found to interfere with both function and survival of the β-cell and thereby promote the development of diabetes. Increased levels of this apolipoprotein affects intracellular Ca-handling and insulin sensitivity, which finally results in impaired glucose homeostasis and diabetes. Interestingly, in a type-1 diabetesrat model lowering of apoCIII delays onset of diabetes. In type-2 diabetes insulin resistance within the pancreatic islets leads to a local increase in apoCIII that promotes inflammation and β-cell dysfunction. Hence, targeting apoCIII may constitute a novel pharmacological strategy to treat both type-1 and type-2 diabetes.
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