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Linking Metabolic Abnormalities to Apoptotic Pathways in Beta Cells in Type 2 Diabetes
Immunology and Diabetes Unit, St Vincent's Institute, Fitzroy, Victoria, 3065 Australia
Department of Medicine, the University of Melbourne, St. Vincent's Hospital, Fitzroy, Victoria, 3065 Australia
The Walter and Eliza Hall Institute, Parkville, Victoria, 3052 Australia
* Author to whom correspondence should be addressed.
Received: 14 February 2013; in revised form: 3 April 2013 / Accepted: 5 April 2013 / Published: 26 April 2013
(This article belongs to the Special Issue Apoptosis
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-1b 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.
Keywords: Type 2 diabetes; pancreatic beta cell; apoptosis; endoplasmic reticulum stress; oxidative stress; NLRP3 inflammasome; Bcl-2 pathway
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MDPI and ACS Style
Wali, J.A.; Masters, S.L.; Thomas, H.E. Linking Metabolic Abnormalities to Apoptotic Pathways in Beta Cells in Type 2 Diabetes. Cells 2013, 2, 266-283.
Wali JA, Masters SL, Thomas HE. Linking Metabolic Abnormalities to Apoptotic Pathways in Beta Cells in Type 2 Diabetes. Cells. 2013; 2(2):266-283.
Wali, Jibran A.; Masters, Seth L.; Thomas, Helen E. 2013. "Linking Metabolic Abnormalities to Apoptotic Pathways in Beta Cells in Type 2 Diabetes." Cells 2, no. 2: 266-283.