Beta-cell preservation with thiazolidinediones.
Progressive beta-cell dysfunction and beta-cell failure are fundamental pathogenic features of type 2 diabetes. Ultimately, the development and continued progression of diabetes is a consequence of the failure of the beta-cell to overcome insulin resistance. Strategies that aim to prevent diabetes must, therefore, ultimately aim to stabilize the progressive decline of the beta-cell. Clinical study evidence from several sources now suggests that thiazolidinediones (TZDs) have profound effects on the beta-cell, such as improving insulin secretory capacity, preserving beta-cell mass and islet structure and protecting beta-cells from oxidative stress, as well as improving measures of beta-cell function, such as insulinogenic index and homeostasis model assessment of beta-cell function (HOMA-%B). Furthermore, intervention studies suggest that TZDs have the potential to delay, stabilize and possibly even prevent the onset on diabetes in high-risk individuals, and these effects appear to accompany improvements in beta-cell function. Here, we review the evidence, from in vitro studies to large intervention trials, for the effects of TZDs on beta-cell function and the consequences for glucose-lowering therapy.
Campbell
Ian W
IW
Victoria Hospital, Kirkcaldy, Fife, Scotland.
Mariz
Segundo
S
D002839:Chromans / Q000494:pharmacology / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000517:prevention & control; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D000077205:Pioglitazone; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D000077288:Troglitazone
D002839:Chromans; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077288:Troglitazone; D000077205:Pioglitazone