Abstract
Pancreatic beta-cell apoptosis is an important feature of islets in type 2 diabetes. Apoptosis can occur through two major pathways, the extrinsic or death receptor mediated pathway, and the intrinsic or Bcl-2-regulated pathway. Hyperglycaemia, hyperlipidaemia and islet amyloid poly-peptide (IAPP) represent important possible causes of increased beta-cell apoptosis. Hyperglycaemia induces islet-cell apoptosis by the intrinsic pathway involving molecules of the Bcl-2 family. High concentrations of palmitate also activate intrinsic apoptosis in islets cells. IAPP oligomers can induce apoptosis by both intrinsic and extrinsic pathways. IL-1β produced through NLRP3 inflammasome activation can also induce islet cell death. Activation of the NLRP3 inflammasome may not be important for glucose or palmitate induced apoptosis in islets but may be important for IAPP mediated cell death. Endoplasmic reticulum (ER) and oxidative stress have been observed in beta cells in type 2 diabetes, and these could be the link between upstream metabolic abnormalities and downstream apoptotic machinery.
Highlights
Apoptosis can occur through two major pathways, the extrinsic or death receptor mediated pathway, and the intrinsic or Bcl-2-regulated pathway
Examination of pancreases obtained from healthy and type 2 diabetic human donors showed that beta-cell mass is decreased and apoptosis is increased in type 2 diabetes [1,2,3]
This review focuses on the molecular details of the type 2 diabetes induced apoptosis in pancreatic islet cells, the beta cells
Summary
Type 2 diabetes is caused by beta-cell dysfunction and declining beta-cell mass in insulin resistant subjects. Apoptosis is difficult to detect in islets because of rapid-turnover and clearance of apoptotic cells by neighboring macrophages. Because of this difficulty, most of the studies of apoptosis in type 2 diabetes have been carried out on animal models. Several animal models have shown loss of beta-cell mass and increased number of TUNEL positive apoptotic beta cells in type 2 diabetes. These include db/db mice [4] and Akita mice [5] that have diabetes caused by different mechanisms. This review focuses on the molecular details of the type 2 diabetes induced apoptosis in pancreatic islet cells, the beta cells
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