Abstract
Type 2 diabetes is increasingly viewed as a disease of insulin deficiency due not only to intrinsic pancreatic beta-cell dysfunction but also to reduction of beta-cell mass. It is likely that, in diabetes-prone subjects, the regulated beta-cell turnover that adapts cell mass to body's insulin requirements is impaired, presumably on a genetic basis. We still have a limited knowledge of how and when this derangement occurs and what might be the most effective therapeutic strategy to preserve beta-cell mass. The animal models of type 2 diabetes with reduced beta-cell mass described in this review can be extremely helpful (a) to have insight into the mechanisms underlying the defective growth or accelerated loss of beta-cells leading to the beta-cell mass reduction; (b) to investigate in prospective studies the mechanisms of compensatory adaptation and subsequent failure of a reduced beta-cell mass. Furthermore, these models are of invaluable importance to test the effectiveness of potential therapeutic agents that either stimulate beta-cell growth or inhibit beta-cell death.
MeSH terms
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Animals
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Cyclic AMP Response Element-Binding Protein / genetics
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Cyclin D2
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Cyclin-Dependent Kinase 4 / deficiency
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Cyclins / deficiency
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Diabetes Mellitus, Experimental / physiopathology
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Diabetes Mellitus, Type 2 / pathology
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Diabetes Mellitus, Type 2 / physiopathology*
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Disease Models, Animal*
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Exenatide
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Fetal Growth Retardation / physiopathology
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Homeodomain Proteins
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Insulin Receptor Substrate Proteins
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Insulin-Secreting Cells / pathology*
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Intracellular Signaling Peptides and Proteins
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Mice
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Mice, Transgenic
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Peptides / therapeutic use
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Phosphoproteins / deficiency
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Proto-Oncogene Proteins c-akt / deficiency
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Rats
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Receptor, Insulin
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Ribosomal Protein S6 Kinases, 70-kDa / deficiency
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Trans-Activators / deficiency
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Venoms / therapeutic use
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eIF-2 Kinase / deficiency
Substances
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Ccnd2 protein, mouse
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Cyclic AMP Response Element-Binding Protein
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Cyclin D2
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Cyclins
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Homeodomain Proteins
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Insulin Receptor Substrate Proteins
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Intracellular Signaling Peptides and Proteins
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Irs2 protein, mouse
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Irs2 protein, rat
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Peptides
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Phosphoproteins
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Trans-Activators
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Venoms
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pancreatic and duodenal homeobox 1 protein
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Exenatide
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Receptor, Insulin
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PERK kinase
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Proto-Oncogene Proteins c-akt
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Ribosomal Protein S6 Kinases, 70-kDa
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eIF-2 Kinase
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Cyclin-Dependent Kinase 4