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The Roles Of Stressed Endoplasmic Reticulum On Type Ii Diabetes

2036 words - 9 pages

The rough endoplasmic reticulum (ER) is the site of synthesis for many proteins in the cell. It also assists in the subsequent protein folding via numerous proteins housed in its lumen. However, the rough ER can be subjected to stress and protein folding may not always be completed or properly executed. ER stress leading to an accumulation of both unfolded and misfolded proteins triggers the unfolded protein response, or UPR. The UPR is a mechanism by which the ER increases its protein folding capacity and decreases its client load, thus enabling it to cope with the stress. However, extended periods of UPR activation due to extreme and prolonged ER stress harms the cell. Correlational and mechanistic research studies have shown that sustained UPR contributes to the pathogenesis of Type II Diabetes—a disorder characterized by raised blood sugar levels due to insulin resistance. Obesity, the most common cause of type II Diabetes, causes ER stress that triggers two UPR signal transduction pathways—the Inositol requiring protein–1 (IRE1) and protein kinase RNA-like ER kinase (PERK) pathways. IRE1 leads to insulin resistance by inactivating an adaptor protein needed for insulin’s interaction with its receptor. PERK amplifies elevated blood sugar levels by activating an apoptotic agent that targets the insulin-producing beta cells of the pancreas. Currently, various medical treatments for Type II Diabetes are being pursued. This includes non-peptide insulin action enhancers, incretins and glucokinase activators.
Type II Diabetes
Insulin is a hormone produced by the pancreas in response to high blood sugar levels (Vijan, 2010). It stimulates cells to uptake glucose, where it can either be metabolized for energy or stored as glycogen (eg. liver and muscle cells) (Vijan, 2010). This allows blood sugar levels to recede back to normal (Vijan, 2010). However, in some cases, insulin receptors on cells are unresponsive and signal transduction initiated by insulin is not carried out (Vijan, 2010). Type II Diabetes is a disorder where blood sugar levels are unusually high due to insulin resistance (Vijan, 2010). Type II Diabetes is caused by obesity, and its symptoms include thirst, frequent urination, and fatigue (Vijan, 2010). In severe cases, it is also characterized by blurred vision and numbness or a tingling sensation on the hands and feet (Vijan, 2010). On the cellular level, the root of type II Diabetes can be traced to problems in the endoplasmic reticulum (Lee and White, 2004).
The role of the ER in the cell
The endoplasmic reticulum (ER) is an organelle in the cell that is responsible for a wide range of functions (Rutkowski and Kaufman, 2004). The smooth endoplasmic reticulum is primarily responsible for lipid synthesis (Rutkowski and Kaufman, 2004).In contrast, the rough endoplasmic reticulum—so-called because it is studded with ribosomes—is the site for co-translational protein synthesis. It also assists in subsequent protein folding (Rutkowski...

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