Apoptosis in pancreatic β-islet cells in Type 2 diabetes
Apoptosis plays important roles in the pathophysiology of Type 2 diabetes mellitus (T2DM). The etiology of T2DM is multifactorial, including obesity-associated insulin resistance, defective insulin secretion, and loss of β-cell mass through β-cell apoptosis. β-cell apoptosis is mediated through a m...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2016-08-01
|
| Series: | Biomolecules & Biomedicine |
| Subjects: | |
| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/919 |
| _version_ | 1797260896344473600 |
|---|---|
| author | Tatsuo Tomita |
| author_facet | Tatsuo Tomita |
| author_sort | Tatsuo Tomita |
| collection | DOAJ |
| description |
Apoptosis plays important roles in the pathophysiology of Type 2 diabetes mellitus (T2DM). The etiology of T2DM is multifactorial, including obesity-associated insulin resistance, defective insulin secretion, and loss of β-cell mass through β-cell apoptosis. β-cell apoptosis is mediated through a milliard of caspase family cascade machinery in T2DM. The glucose-induced insulin secretion is the principle pathophysiology of diabetes and insufficient insulin secretion results in chronic hyperglycemia, diabetes. Recently, hyperglycemia-induced β-cell apoptosis has been extensively studied on the balance of pro-apoptotic Bcl-2 proteins (Bad, Bid, Bik, and Bax) and anti-apoptotic Bcl family (Bcl-2 and Bcl-xL) toward apoptosis in vitro isolated islets and insulinoma cell culture. Apoptosis can only occur when the concentration of pro-apoptotic Bcl-2 exceeds that of anti-apoptotic proteins at the mitochondrial membrane of the intrinsic pathway. A bulk of recent research on hyperglycemia-induced apoptosis on β-cells unveiled complex details on glucose toxicity on β-cells in molecular levels coupled with cell membrane potential by adenosine triphosphate generation through K+ channel closure, opening Ca2+ channel and plasma membrane depolarization. Furthermore, animal models using knockout mice will shed light on the basic understanding of the pathophysiology of diabetes as a glucose metabolic disease complex, on the balance of anti-apoptotic Bcl family and pro-apoptotic genes. The cumulative knowledge will provide a better understanding of glucose metabolism at a molecular level and will lead to eventual prevention and therapeutic application for T2DM with improving medications.
|
| first_indexed | 2024-04-24T23:32:36Z |
| format | Article |
| id | doaj.art-9318e7325ba44229a0385376751ce724 |
| institution | Directory Open Access Journal |
| issn | 2831-0896 2831-090X |
| language | English |
| last_indexed | 2024-04-24T23:32:36Z |
| publishDate | 2016-08-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
| record_format | Article |
| series | Biomolecules & Biomedicine |
| spelling | doaj.art-9318e7325ba44229a0385376751ce7242024-03-15T14:31:56ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2016-08-0116310.17305/bjbms.2016.919113Apoptosis in pancreatic β-islet cells in Type 2 diabetesTatsuo Tomita0Oregon Health and Science University Apoptosis plays important roles in the pathophysiology of Type 2 diabetes mellitus (T2DM). The etiology of T2DM is multifactorial, including obesity-associated insulin resistance, defective insulin secretion, and loss of β-cell mass through β-cell apoptosis. β-cell apoptosis is mediated through a milliard of caspase family cascade machinery in T2DM. The glucose-induced insulin secretion is the principle pathophysiology of diabetes and insufficient insulin secretion results in chronic hyperglycemia, diabetes. Recently, hyperglycemia-induced β-cell apoptosis has been extensively studied on the balance of pro-apoptotic Bcl-2 proteins (Bad, Bid, Bik, and Bax) and anti-apoptotic Bcl family (Bcl-2 and Bcl-xL) toward apoptosis in vitro isolated islets and insulinoma cell culture. Apoptosis can only occur when the concentration of pro-apoptotic Bcl-2 exceeds that of anti-apoptotic proteins at the mitochondrial membrane of the intrinsic pathway. A bulk of recent research on hyperglycemia-induced apoptosis on β-cells unveiled complex details on glucose toxicity on β-cells in molecular levels coupled with cell membrane potential by adenosine triphosphate generation through K+ channel closure, opening Ca2+ channel and plasma membrane depolarization. Furthermore, animal models using knockout mice will shed light on the basic understanding of the pathophysiology of diabetes as a glucose metabolic disease complex, on the balance of anti-apoptotic Bcl family and pro-apoptotic genes. The cumulative knowledge will provide a better understanding of glucose metabolism at a molecular level and will lead to eventual prevention and therapeutic application for T2DM with improving medications. https://www.bjbms.org/ojs/index.php/bjbms/article/view/919Amyloidapoptosisβ-cellscaspasehyperglycemiainsulin |
| spellingShingle | Tatsuo Tomita Apoptosis in pancreatic β-islet cells in Type 2 diabetes Biomolecules & Biomedicine Amyloid apoptosis β-cells caspase hyperglycemia insulin |
| title | Apoptosis in pancreatic β-islet cells in Type 2 diabetes |
| title_full | Apoptosis in pancreatic β-islet cells in Type 2 diabetes |
| title_fullStr | Apoptosis in pancreatic β-islet cells in Type 2 diabetes |
| title_full_unstemmed | Apoptosis in pancreatic β-islet cells in Type 2 diabetes |
| title_short | Apoptosis in pancreatic β-islet cells in Type 2 diabetes |
| title_sort | apoptosis in pancreatic β islet cells in type 2 diabetes |
| topic | Amyloid apoptosis β-cells caspase hyperglycemia insulin |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/919 |
| work_keys_str_mv | AT tatsuotomita apoptosisinpancreaticbisletcellsintype2diabetes |