Animal models of type 2 diabetes with reduced pancreatic beta-cell mass

Int J Biochem Cell Biol. 2006;38(5-6):873-93. doi: 10.1016/j.biocel.2005.09.007. Epub 2005 Oct 4.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclin D2
  • Cyclin-Dependent Kinase 4 / deficiency
  • Cyclins / deficiency
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Disease Models, Animal*
  • Exenatide
  • Fetal Growth Retardation / physiopathology
  • Homeodomain Proteins
  • Insulin Receptor Substrate Proteins
  • Insulin-Secreting Cells / pathology*
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Transgenic
  • Peptides / therapeutic use
  • Phosphoproteins / deficiency
  • Proto-Oncogene Proteins c-akt / deficiency
  • Rats
  • Receptor, Insulin
  • Ribosomal Protein S6 Kinases, 70-kDa / deficiency
  • Trans-Activators / deficiency
  • Venoms / therapeutic use
  • eIF-2 Kinase / deficiency

Substances

  • Ccnd2 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Cyclin D2
  • Cyclins
  • Homeodomain Proteins
  • Insulin Receptor Substrate Proteins
  • Intracellular Signaling Peptides and Proteins
  • Irs2 protein, mouse
  • Irs2 protein, rat
  • Peptides
  • Phosphoproteins
  • Trans-Activators
  • Venoms
  • pancreatic and duodenal homeobox 1 protein
  • Exenatide
  • Receptor, Insulin
  • PERK kinase
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • eIF-2 Kinase
  • Cyclin-Dependent Kinase 4