The Cell Biology Of Systemic Insulin Function
The cell biology of systemic insulin function Victoria L. Tokarz, View ORCID Profile Patrick E. MacDonald, View ORCID Profile Amira Klip Correspondence email Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, CanadaDepartment of Physiology, University of Toronto, Toronto, Ontario, Canada Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, CanadaDepartment of Physiology, University of Toronto, Toronto, Ontario, CanadaDepartment of Biochemistry, University of Toronto, Toronto, Ontario, Canada Insulin is the paramount anabolic hormone, promoting carbon energy deposition in the body. Its synthesis, quality control, delivery, and action are exquisitely regulated by highly orchestrated intracellular mechanisms in different organs or stations of its bodily journey. In this Beyond the Cell review, we focus on these five stages of the journey of insulin through the body and the captivating cell biology that underlies the interaction of insulin with each organ. We first analyze insulins biosynthesis in and export from the -cells of the pancreas. Next, we focus on its first pass and partial clearance in the liver with its temporality and periodicity linked to secretion. Continuing the journey, we briefly describe insulins action on the blood vasculature and its still-debated mechanisms of exit from the capillary beds. Once in the parenchymal interstitium of muscle and adipose tissue, insulin promotes glucose uptake into myofibers and adipocytes, and we elaborate on the intricate signaling and vesicle traffic mechanisms that underlie this fundamental function. Finally, we touch upon the renal degradation of insulin to end its action. Cellular discernment of insulins availability and action should prove critical to understanding its pivotal Continue reading >>
Insulin's Role In The Human Body
Insulin is a hormone produced by the pancreas that has a number of important functions in the human body, particularly in the control of blood glucose levels and preventing hyperglycemia. It also has an effect on several other areas of the body, including the synthesis of lipids and regulation of enzymatic activity. Insulin and Metabolic Processes The most important role of insulin in the human body is its interaction with glucose to allow the cells of the body to use glucose as energy. The pancreas usually produces more insulin in response to a spike in blood sugar level, for example after eating a meal high in energy. This is because the insulin acts as a “key” to open up the cells in the body and allows the glucose to be used as an energy source. Additionally, when there is excess glucose in the bloodstream, known as hyperglycemia, insulin encourages the storage of glucose as glycogen in the liver, muscle and fat cells. These stores can then be used at a later date when energy requirements are higher. As a result of this, there is less insulin in the bloodstream, and normal blood glucose levels are restored. Insulin stimulates the synthesis of glycogen in the liver, but when the liver is saturated with glycogen, an alternative pathway takes over. This involves the uptake of additional glucose into adipose tissue, leading to the synthesis of lipoproteins. Results Without Insulin In the absence of insulin, the body is not able to utilize the glucose as energy in the cells. As a result, the glucose remains in the bloodstream and can lead to high blood sugar, known as hyperglycemia. Chronic hyperglycemia is characteristic of diabetes mellitus and, if untreated, is associated with severe complications, such as damage to the nervous system, eyes, kidneys and extremitie Continue reading >>
This article is about the insulin protein. For uses of insulin in treating diabetes, see insulin (medication). Not to be confused with Inulin. Insulin (from Latin insula, island) is a peptide hormone produced by beta cells of the pancreatic islets, and it is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into fat, liver and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat. Beta cells are sensitive to glucose concentrations, also known as blood sugar levels. When the glucose level is high, the beta cells secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited. Their neighboring alpha cells, by taking their cues from the beta cells, secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high. Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin. The secretion of insulin and glucagon into the Continue reading >>
How Insulin Works In The Body
By Elizabeth Woolley | Reviewed by Richard N. Fogoros, MD Science Photo Library - SCIEPRO/Brand X Pictures/Getty Images Insulin is a hormone that has a hand in several processes in your body. Not only does it assist with metabolizing carbohydrates and storing glucose for energy in cells, it also helps utilize the fat, protein, and certain minerals you eat. Because this hormone is so important in helping your body use the foods you ingest, a problem with insulin can have widespread effects on all of your body's systems, tissues, and organseither directly or indirectly. If you have type 2 diabetes, learning how insulin works can help you understand why so many other medical conditions are associated with diabetes, why certain lifestyle practices are beneficial, and how your body reacts to food. Insulin is a hormone made up of a small polypeptide protein that is secreted by the pancreas, which acts as both an endocrine and exocrine gland. Endocrine glands are the system of glands that secrete hormones to regulate body functions, whereasexocrine glands aid in digestion. The pancreas sits behind the stomach, nestled in the curve of the duodenum (the first part of the small intestine), and contains clusters of cells called islets of Langerhans. Islets are made up of beta cells, which produce and release insulin into the bloodstream. Insulin affects carbohydrate, protein, and fat metabolism. Your body breaks these nutrients down into sugar molecules, amino acid molecules, and lipid molecules. The body can also store and reassemble these molecules into more complex forms. Insulin causes the storage of these nutrients, while another pancreatic hormone called glucagon releases them from storage. Insulin is involved in your body's careful balancing act to keep your blood sugar le Continue reading >>
What Is Insulin?
Essential for life, the hormone insulin regulates many metabolic processes that provide cells with needed energy. Understanding insulin, what insulin does, and how it affects the body, is important to your overall health. Tucked away behind the stomach is an organ called the pancreas, which produces insulin. Insulin production is regulated based on blood sugar levels and other hormones in the body. In a healthy individual, insulin production and release is a tightly regulated process, allowing the body to balance its metabolic needs. What does insulin do? Insulin allows the cells in the muscles, fat and liver to absorb glucose that is in the blood. The glucose serves as energy to these cells, or it can be converted into fat when needed. Insulin also affects other metabolic processes, such as the breakdown of fat or protein. Problems with insulin production or use The most common problem associated with insulin is diabetes. Diabetes occurs when the body either does not secrete enough insulin or when the body no longer uses the insulin it secretes effectively. Diabetes falls into two categories: Type 1 diabetes occurs when the pancreas cannot produce insulin sufficiently to meet its own needs. This commonly occurs in children, and while an exact cause has not been found, many consider it to be an autoimmune disease. Some symptoms of type 1 diabetes include tiredness, increased urination and thirst, and problems with vision. Type 2 diabetes is more commonly associated with adults and lifestyle choices. People with type 2 diabetes will produce insulin but often not enough for their body's needs. They may also struggle to use the insulin they produce effectively. Patients may not know they have type 2 diabetes until they have an annual checkup, as symptoms tend to be mild un Continue reading >>
The Role Of Insulin In The Body
Tweet Insulin is a hormone which plays a key role in the regulation of blood glucose levels. A lack of insulin, or an inability to adequately respond to insulin, can each lead to the development of the symptoms of diabetes. In addition to its role in controlling blood sugar levels, insulin is also involved in the storage of fat. Insulin is a hormone which plays a number of roles in the body’s metabolism. Insulin regulates how the body uses and stores glucose and fat. Many of the body’s cells rely on insulin to take glucose from the blood for energy. Insulin and blood glucose levels Insulin helps control blood glucose levels by signaling the liver and muscle and fat cells to take in glucose from the blood. Insulin therefore helps cells to take in glucose to be used for energy. If the body has sufficient energy, insulin signals the liver to take up glucose and store it as glycogen. The liver can store up to around 5% of its mass as glycogen. Some cells in the body can take glucose from the blood without insulin, but most cells do require insulin to be present. Insulin and type 1 diabetes In type 1 diabetes, the body produces insufficient insulin to regulate blood glucose levels. Without the presence of insulin, many of the body’s cells cannot take glucose from the blood and therefore the body uses other sources of energy. Ketones are produced by the liver as an alternative source of energy, however, high levels of the ketones can lead to a dangerous condition called ketoacidosis. People with type 1 diabetes will need to inject insulin to compensate for their body’s lack of insulin. Insulin and type 2 diabetes Type 2 diabetes is characterised by the body not responding effectively to insulin. This is termed insulin resistance. As a result the body is less able to t Continue reading >>
Regulation Of Insulin Action At The Cellular Level.
Abstract Insulin regulates cellular metabolic reactions by its action on the plasma membrane, intracellular enzymes and the nucleus. The first stage in the propagation of the insulin signal is the coupling of insulin to specific receptors at the cell surface. The exact mechanism whereby the transmembrane signalling mechanism (s) results in different insulin-mediated cellular effects is not known. However, the insulin receptor tyrosine kinase, the expression of second messengers, and the action of protein kinase C may, either individually or in combination, mediate some of the insulin effects, such as translocation and activation of glucose transporter proteins. Insulin resistance in clinical conditions such as insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM), hypertension and obesity may be acquired to a large extent, and is thus partially reversible. Regulatory factors in insulin sensitivity, such as free fatty acids, counterregulatory hormones and blood glucose level, play an important role in the metabolic control and pathogenesis of insulin resistance in man. Continue reading >>
The Action Of Insulin On Cells
The Action of Insulin on Cells: A Speculation on Mechanism of Insulin Action on Muscle focuses on metabolic alterations induced in man or animals by insulin deficiency or excess, t ... read full description The Action of Insulin on Cells: A Speculation on Mechanism of Insulin Action on Muscle focuses on metabolic alterations induced in man or animals by insulin deficiency or excess, t ... read full description The Action of Insulin on Cells: A Speculation on Mechanism of Insulin Action on Muscle focuses on metabolic alterations induced in man or animals by insulin deficiency or excess, tissues responsive to insulin, effects of insulin on muscles, adipose tissues, and liver, and the chemical structure and properties of insulin. The publication first offers information on tissues acted upon by insulin, insulin and muscle, and insulin and the liver. Discussions focus on amino acid incorporation into liver protein, liver enzymes and insulin, glucose output and uptake, insulin and incorporation of amino acids into peptides, and glucose uptake and glycogen synthesis. The text then examines the relationships of insulin and adipose tissues and insulin and cell permeability. The book takes a look at the interactions of insulin, pituitary factors, and adrenal hormones in isolated tissues and insulin effects in cell-free systems. Topics include thiamine phosphorylation, oxygen consumption and oxidative phosphorylation, glycogen synthesis in diaphragm fragments, amino acid incorporation into proteins of isolated tissues, and utilization of carbohydrates by isolated tissues. The book also ponders on the structure and properties of insulin and speculations on insulin action. The publication is a valuable source of information for researchers interested in the mechanism of insulin ac Continue reading >>
What Is Insulin?
Insulin is a hormone made by the pancreas that allows your body to use sugar (glucose) from carbohydrates in the food that you eat for energy or to store glucose for future use. Insulin helps keeps your blood sugar level from getting too high (hyperglycemia) or too low (hypoglycemia). The cells in your body need sugar for energy. However, sugar cannot go into most of your cells directly. After you eat food and your blood sugar level rises, cells in your pancreas (known as beta cells) are signaled to release insulin into your bloodstream. Insulin then attaches to and signals cells to absorb sugar from the bloodstream. Insulin is often described as a “key,” which unlocks the cell to allow sugar to enter the cell and be used for energy. If you have more sugar in your body than it needs, insulin helps store the sugar in your liver and releases it when your blood sugar level is low or if you need more sugar, such as in between meals or during physical activity. Therefore, insulin helps balance out blood sugar levels and keeps them in a normal range. As blood sugar levels rise, the pancreas secretes more insulin. If your body does not produce enough insulin or your cells are resistant to the effects of insulin, you may develop hyperglycemia (high blood sugar), which can cause long-term complications if the blood sugar levels stay elevated for long periods of time. Insulin Treatment for Diabetes People with type 1 diabetes cannot make insulin because the beta cells in their pancreas are damaged or destroyed. Therefore, these people will need insulin injections to allow their body to process glucose and avoid complications from hyperglycemia. People with type 2 diabetes do not respond well or are resistant to insulin. They may need insulin shots to help them better process Continue reading >>
What Is Insulin?
Insulin is a hormone; a chemical messenger produced in one part of the body to have an action on another. It is a protein responsible for regulating blood glucose levels as part of metabolism.1 The body manufactures insulin in the pancreas, and the hormone is secreted by its beta cells, primarily in response to glucose.1 The beta cells of the pancreas are perfectly designed "fuel sensors" stimulated by glucose.2 As glucose levels rise in the plasma of the blood, uptake and metabolism by the pancreas beta cells are enhanced, leading to insulin secretion.1 Insulin has two modes of action on the body - an excitatory one and an inhibitory one:3 Insulin stimulates glucose uptake and lipid synthesis It inhibits the breakdown of lipids, proteins and glycogen, and inhibits the glucose pathway (gluconeogenesis) and production of ketone bodies (ketogenesis). What is the pancreas? The pancreas is the organ responsible for controlling sugar levels. It is part of the digestive system and located in the abdomen, behind the stomach and next to the duodenum - the first part of the small intestine.4 The pancreas has two main functional components:4,5 Exocrine cells - cells that release digestive enzymes into the gut via the pancreatic duct The endocrine pancreas - islands of cells known as the islets of Langerhans within the "sea" of exocrine tissue; islets release hormones such as insulin and glucagon into the blood to control blood sugar levels. Islets are highly vascularized (supplied by blood vessels) and specialized to monitor nutrients in the blood.2 The alpha cells of the islets secrete glucagon while the beta cells - the most abundant of the islet cells - release insulin.5 The release of insulin in response to elevated glucose has two phases - a first around 5-10 minutes after g Continue reading >>
What Is Insulin Resistance?
Insulin is a hormone produced by the pancreas that helps unlock the body's cells so that sugar (glucose) from the food we eat can be used by the cells for energy. In people with type 2 diabetes, a combination of problems occurs, and scientists aren't really sure which is the chicken and which is the egg. The person's body may not be producing enough insulin to meet their needs, so some glucose can't get into the cells. Glucose remains in the bloodstream, causing high blood glucose levels. In many cases, the person may actually be producing more insulin than one might reasonably expect that person to need to convert the amount of food they've eaten at a meal into energy. Their pancreas is actually working overtime to produce more insulin because the body's cells are resistant to the effects of insulin. Basically the cells, despite the presence of insulin in the bloodstream, don't become unlocked and don't let enough of the glucose in the blood into the cells. Scientists don't know exactly what causes this insulin resistance, and many expect that there are several different defects in the process of unlocking cells that cause insulin resistance. Medications for type 2 diabetes focus on different parts of this insulin-cell interaction to help improve blood glucose control. Some medications stimulate the pancreas to produce more insulin. Others improve how the body uses insulin by working on this insulin resistance. Physical activity also seems to improve the body's ability to use insulin by decreasing insulin resistance, which is why activity is so important in diabetes management. Continue reading >>
The Effect Of Insulin On The Growth And Metabolism Of The Human Diploid Cell,
In a confluent culture of WI-38 cells the membrane area available for nutrient uptake is greatly reduced and the possibility exists that this reduction in uptake capacity of the cell is a contributory factor in contact inhibition. Insulin has been reported by many authors to facilitate glucose uptake and also to stimulate protein, DNA and RNA synthesis, glycolysis, pino-cytosis and growth in cultured cells. The effect of insulin on WI-38 cells was determined, therefore, to find out whether it enabled the cell to escape from contact inhibition of growth. The action of insulin was found to be dependent upon medium composition. Growth and protein synthesis were stimulated in Eagle's minimal essential medium, but not when this medium was supplemented with glucose and glutamine. Apparently insulin is only effective when high-energy compounds become limiting. Whilst insulin did not induce any post-confluent division, the protein content of cells was increased by 30%, and this was correlated with an increased rate of protein synthesis. Despite this increased activity in protein metabolism, the utilization of amino acids was less in the presence of insulin indicating that a control mechanism for more economical utilization of amino acids for protein synthesis was activated by insulin. Insulin had no effect on RNA synthesis, and only a slight inhibitory effect on DNA synthesis. Evidence was produced suggesting that insulin blocked cell division and encouraged differentiation. Glucose uptake and incorporation into the cell was stimulated by insulin, and this was especially noticeable after the cell sheet became confluent. The turnover of labelled glucose and derivatives was also enhanced by insulin and this was accompanied by a much higher rate of lactic acid production. It is co Continue reading >>
Nih Study Shows How Insulin Stimulates Fat Cells To Take In Glucose
Findings could aid in understanding diabetes, related conditions. Using high-resolution microscopy, researchers at the National Institutes of Health have shown how insulin prompts fat cells to take in glucose in a rat model. The findings were reported in the Sept. 8 issue of the journal Cell Metabolism. By studying the surface of healthy, live fat cells in rats, researchers were able to understand the process by which cells take in glucose. Next, they plan to observe the fat cells of people with varying degrees of insulin sensitivity, including insulin resistance — considered a precursor to type 2 diabetes (These observations may help identify the interval when someone becomes at risk for developing diabetes. "What we're doing here is actually trying to understand how glucose transporter proteins called GLUT4 work in normal, insulin-sensitive cells," said Karin G. Stenkula, Ph.D., a researcher at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and a lead author of the paper. "With an understanding of how these transporters in fat cells respond to insulin, we could detect the differences between an insulin-sensitive cell and an insulin-resistant cell, to learn how the response becomes impaired. We hope to identify when a person becomes pre-diabetic, before they go on to develop diabetes." Glucose, a simple sugar, provides energy for cell functions. After food is digested, glucose is released into the bloodstream. In response, the pancreas secretes insulin, which directs the muscle and fat cells to take in glucose. Cells obtain energy from glucose or convert it to fat for long-term storage. Like a key fits into a lock, insulin binds to receptors on the cell's surface, causing GLUT4 molecules to come to the cell's surface. As their name impli Continue reading >>
The Effects Of Insulin On The Body
Insulin is a hormone produced by the pancreas. Its function is to allow other cells to transform glucose into energy throughout your body. Without insulin, cells are starved for energy and must seek an alternate source. This can lead to life-threatening complications. The Effects of Insulin on the Body Insulin is a natural hormone produced in the pancreas. When you eat, your pancreas releases insulin to help your body make energy out of sugars (glucose). It also helps you store energy. Insulin is a vital part of metabolism. Without it, your body would cease to function. In type 1 diabetes, the pancreas is no longer able to produce insulin. In Type 2 diabetes, the pancreas initially produces insulin, but the cells of your body are unable to make good use of the insulin (insulin resistance). Uncontrolled diabetes allows glucose to build up in the blood rather than being distributed to cells or stored. This can wreak havoc with virtually every part of your body. Complications of diabetes include kidney disease, nerve damage, eye problems, and stomach problems. People with Type 1 diabetes need insulin therapy to live. Some people with Type 2 diabetes must also take insulin therapy to control blood sugar levels and avoid complications. Insulin is usually injected into the abdomen, but it can also be injected into the upper arms, thighs, or buttocks. Injection sites should be rotated within the same general location. Frequent injections in the same spot can cause fatty deposits that make delivery of insulin more difficult. Some people use a pump, which delivers insulin through a catheter placed underneath the skin of the abdomen. When you eat, food travels to your stomach and small intestines where it is broken down into nutrients. The nutrients are absorbed and distributed v Continue reading >>
You And Your Hormones
What is insulin? Insulin is a hormone made by an organ located behind the stomach called the pancreas. Here, insulin is released into the bloodstream by specialised cells called beta cells found in areas of the pancreas called islets of langerhans (the term insulin comes from the Latin insula meaning island). Insulin can also be given as a medicine for patients with diabetes because they do not make enough of their own. It is usually given in the form of an injection. Insulin is released from the pancreas into the bloodstream. It is a hormone essential for us to live and has many effects on the whole body, mainly in controlling how the body uses carbohydrate and fat found in food. Insulin allows cells in the muscles, liver and fat (adipose tissue) to take up sugar (glucose) that has been absorbed into the bloodstream from food. This provides energy to the cells. This glucose can also be converted into fat to provide energy when glucose levels are too low. In addition, insulin has several other metabolic effects (such as stopping the breakdown of protein and fat). How is insulin controlled? When we eat food, glucose is absorbed from our gut into the bloodstream. This rise in blood glucose causes insulin to be released from the pancreas. Proteins in food and other hormones produced by the gut in response to food also stimulate insulin release. However, once the blood glucose levels return to normal, insulin release slows down. In addition, hormones released in times of acute stress, such as adrenaline, stop the release of insulin, leading to higher blood glucose levels. The release of insulin is tightly regulated in healthy people in order to balance food intake and the metabolic needs of the body. Insulin works in tandem with glucagon, another hormone produced by the pan Continue reading >>