title: The pancreatic beta-cell in human Type 2 diabetes.
abstract: OBJECTIVE
  There is growing evidence that the beta-cell is central to the development of Type 2 diabetes. In this brief review we discuss the factors predisposing to beta-cell dysfunction and some characteristics of islet cells in Type 2 diabetes.
  
  
  RESULTS
  Several genes have been associated with islet cell dysfunction in Type 2 diabetes, including those encoding for transcription factors, glucose metabolism proteins, molecules of the insulin signaling pathways, and several others. On the other hand, many environmental factors can directly or indirectly affect pancreatic islet cells, and possibly contribute to the development and/or progression of Type 2 diabetes. In this regard, the role of prolonged exposure to high glucose (glucotoxicity) and high fatty acid (lipotoxicity) concentrations seems to be of particular relevance. More recently, it has been possible to directly evaluate some properties of pancreatic islets prepared from Type 2 diabetic donors. Consistently, a marked decrease in insulin secretion during glucose stimulation has been found, although the secretory response to amino acids or sulphonylurea is usually less severely affected. In addition, increased beta-cell apoptosis in Type 2 diabetes islets has been reported. Interestingly, experimental data show that in vitro manipulation of human Type 2 diabetes islets by agents that are able to reduce oxidative stress can improve beta-cell function and survival.
  
  
  CONCLUSIONS
  Available data are consistent with the concept that the defect of the beta-cell is of primary importance in Type 2 diabetes; the evidence that some alterations in Type 2 diabetes beta-cells can be reverted, at least in vitro, may open new perspectives in the treatment of this disease.
authors.affiliation: Department of Endocrinology and Metabolism, Metabolic Section, University of Pisa, Pisa, Italy. marchant@immr.med.unipi.it
authors.forename: Piero
authors.initials: P
authors.lastname: Marchetti
authors.forename: Stefano
authors.initials: S
authors.lastname: Del Prato
authors.forename: Roberto
authors.initials: R
authors.lastname: Lupi
authors.forename: Silvia
authors.initials: S
authors.lastname: Del Guerra
mesh_terms: D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D005227:Fatty Acids / Q000009:adverse effects / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin