The beta-cell in human type 2 diabetes.
beta-cell dysfunction is central to the onset and progression of type 2 diabetes. Reduced islet number and/or diminished beta-cell mass/volume in the pancreas of type 2 diabetic subjects have been reported by many authors, mainly due to increased apoptosis not compensated for by adequate regeneration. In addition, ultrastructural analysis has shown reduced insulin granules and morphological changes in several beta-cell organelles, including mitochondria and endoplasmic reticulum. Several quantitative and qualitative defects of beta-cell function have been described in human type 2 diabetes using isolated islets, including alterations in early phase, glucose-stimulated insulin release. These survival and functional changes are accompanied by modifications of islet gene and protein expression. The impact of genotype in affecting beta-cell function and survival has been addressed in a few studies, and a number of gene variants have been associated with beta-cell dysfunction. Among acquired factors, the role of glucotoxicity and lipotoxicity could be of particular importance, due to the potential deleterious impact of elevated levels of glucose and/or free fatty acids in the natural history of beta-cell damage. More recently, it has been proposed that inflammation might also play a role in the dysfunction of the beta-cell in type 2 diabetes. Encouraging, although preliminary, data show that some of these defects might be directly counteracted, at least in part, by appropriate in vitro pharmacological intervention.
Marchetti
Piero
P
Department of Endocrinology and Metabolism, Cisanello Hospital, 56124 Pisa, Italy. marchant@immr.med.unipi.it
Lupi
Roberto
R
Del Guerra
Silvia
S
Bugliani
Marco
M
Marselli
Lorella
L
Boggi
Ugo
U
D017209:Apoptosis; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D018450:Disease Progression; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology*; D007515:Islets of Langerhans / Q000166:cytology; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D012038:Regeneration
D007328:Insulin