Repair of pancreatic beta-cells. A relevant phenomenon in early IDDM?
Most studies dealing with the pathogenesis of IDDM have emphasized the immune assault against beta-cells. In this perspective, we review the data that suggest that the beta-cell destruction of IDDM depends on a balance between beta-cell damage and repair. The progressive beta-cell damage leading to IDDM seems to follow markedly different temporal courses in individual patients. Some individuals at high risk for developing IDDM, and presenting with impaired beta-cell function, appear to recover beta-cell function when followed prospectively. Moreover, after the clinical onset of IDDM, most patients experience a transitory period of improved insulin secretion. In vitro and in vivo experimental data suggest that beta-cells are indeed able to repair themselves after damage. Dispersed beta-cells or whole islets can survive and regain their function after a toxic assault. Furthermore, the abnormal insulin release and glucose oxidation of islets isolated from NOD mice during the prediabetic period is completely restored after 1 wk in tissue culture. Finally, treatment of NOD mice with monoclonal antibodies directed against infiltrating T-cells reverses the altered glucose metabolism of beta-cells. Note that beta-cell repair after exposure to different toxic agents can be enhanced both in vivo and in vitro. Potential enhancers of beta-cell repair are nicotinamide, glucose, protein-rich diets, and branched chain amino acids. A basic question that remains to be answered is the nature of the repair mechanisms triggered by beta-cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medical Cell Biology, Uppsala University, Sweden.
D L
DL
Eizirik
S
S
Sandler
J P
JP
Palmer
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology* / Q000503:physiopathology; D004044:Dietary Proteins / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D016688:Mice, Inbred NOD; D009536:Niacinamide / Q000494:pharmacology; D011446:Prospective Studies
D004044:Dietary Proteins; D009536:Niacinamide; D005947:Glucose