Stem Cells and Diabetes The Present August 26, 2010

Background Diabetes affects more people and causes more deaths each year than breast cancer and AIDS combined. The American Diabetes Association estimates that 16 million people, 5.9% of the U.S. population, currently has some type of diabetes. NIH Stem Cell Information Center http://stemcells.nih.gov/info/scireport/chapter7.asp The above refers to all types of diabetes: type 1, type 2, and gestational.

What is diabetes? group of diseases abnormally high levels of glucose in the blood possible complications include blindness, stroke, kidney failure, heart disease, poor circulation, and amputation According to the National Institutes of Health publication Resource for Stem Cell Research, http://stemcells.nih.gov/info/scireport/chapter7.asp, diabetes is a group of diseases characterized by abnormally high levels of glucose in the blood.

Type 1 Diabetes juvenile-onset typically affects children and young adults immune system attacks and destroys beta cells (β cells) in the islets of Langerhans of the pancreas that normally produce insulin glucose does not enter the cells and therefore accumulates in the blood Type 1 diabetes is classified as an autoimmune disease. Islets are small clusters of cells located in the pancreas. These will be discussed more on future slides.

Type 2 Diabetes adult-onset diabetes typically affects older, sedentary, and overweight individuals with a family history of diabetes body cannot use insulin effectively due to insulin resistance, glucose accumulates in the blood Type 2 diabetes mellitus is characterized by the resistance of peripheral tissues to insulin and a relative deficiency of insulin secretion. Dysfunction of the pancreatic β cell is a key defect in type 2 diabetes. However, it’s exact relationship to insulin resistance is unclear. It is known that insulin receptors in pancreatic β cells play an important role in glucose sensing. Defects in insulin signaling at the level of the β cell may contribute to the observed alterations in insulin secretion in type 2 diabetes.

Role of Pancreas in Diabetes Comments: The pancreas is approximately the size of a banana located in the gut near the stomach and intestines. It has major exocrine and endocrine functions. Islets in the pancreas measure the amount of glucose in the blood and secrete insulin so that other cells will take up the glucose. Each year approximately 1,300 people with type 1 diabetes receive whole organ transplants. After approximately one year, 83% are symptom free and no longer need to use insulin to maintain the appropriate level of glucose in the blood. The demand for organs exceeds the availability. Also, recipients must take drugs to suppress the immune system. This opens them up to a number of other health issues such as infections and cancer. This is because many immunosuppressants shut down the entire immune system, not just one specific part of it. Doctors have also tried to cure diabetes by injecting patients with pancreatic islet cells. These patients must also take immunosuppressant drugs which increase the metabolic demand and ultimately tax the islets so that they can no longer produce insulin. Only about 8% of islet transplants have been successful. Source: The National Institute of Health Stem Cell Information Center <http://stemcells.nih.gov/info/scireport/chapter7.asp>

What is insulin? peptide hormone synthesized within the β cells of the islets of Langerhans located in the pancreas affects metabolism and other body functions causes cells in the liver, muscle, and fat tissue to take up glucose from the bloodstream

Role of Pancreas in Diabetes Comments: Somatostatin is a peptide hormone that regulates the endocrine system. It suppresses the release of gastrointestinal hormones. When somatostatin is released from pancreatic delta cells located in the islets of Langerhans, insulin release by the beta cells is inhibited. Somatostatin also affects neurotransmission and cell proliferation. Glucagon is also important in carbohydrate metabolism. It is another hormone produced by the pancreas and is released when the blood glucose level is low. It stimulates the liver to convert stored glycogen into glucose and release it into the blood. Its action is opposite to that of insulin. Pancreatic polypeptide (PP) is secreted by cells in the pancreas. The function of PP is to regulate the secretion activities of the pancreas (both endocrine and exocrine). All three of these cells are important in maintaining homeostasis through feedback mechanisms. For a nice graphic go to http://static.howstuffworks.com/gif/diabetes-glucose-regulation.gif

Question: In type I diabetics, is it possible to get  cells to produce insulin? two possible sources of  cells existing  cells adult stem cells

What are adult stem cells? They are: undifferentiated cells that occur in differentiated tissue able to make identical copies of themselves able to yield specialized cell types of the tissue from which they originated do not replicate indefinitely in culture

Researchers are Investigating: Is it possible to activate the differentiation of adult stem cells present in the pancreas in order to produce needed insulin in type I diabetics? What advantage/disadvantage would this have over organ/islet transplantation or insulin injection?

Researchers Would Need to Know: Are there adult stem cells present in the pancreas that differentiate into beta cells? Are adult pancreatic beta cells formed by self-duplication, stem cell differentiation, or a combination of the two processes?

Mouse-Model Study A pulse-chase experiment performed by Professor Douglas Melton and his team provides important information about how beta cells are replaced. 1. In molecular biology, a pulse-chase analysis is a method for examining a cellular process over time. A labeled compound is injected (pulse) into the organism. The fate of the compound is followed over a period of time (chase). For example, a selected cell or a group of cells is exposed to a labeled compound (the pulse). The labeled compound is incorporated into the system being studied. Time is allowed to pass (from minutes to years) so that the labeled compound is used in the synthesis of the product being studied (the chase). 2. Have students read through and complete the Pulse-Chase Primer followed by chapters #31 and #32 from Lecture One on the “Potent Biology” DVD. Dr. Melton explains the set up of his pulse-chase experiment. 3. Next introduce the activity: “Are adult pancreatic beta cells formed by self-duplication or stem cell differentiation?” 4. After completing the activity, “Are adult pancreatic beta cells formed by self-duplication or stem cell differentiation?”, show students the following chapters in Lecture One of “Potent Biology: Stem Cells, Cloning, and Regeneration” #31 Some cell types replenish by division, not by stem cells #32 A pulse-chase experiment on pancreatic cell replacement #33 New pancreatic beta cells are from division, not stem cells #34 In type I diabetes, no new beta cells can be made

Keep in mind that cells are replaced by: Adult stem cells Mitotic division of existing cells Combination of the two Dr. Melton and his colleagues wanted to know how β cells are being replaced. The pulse-chase experiment was a way to discover this information.