The Link Between The Gut And The Pancreas
Insulin is produced in higher amounts when sugar passes through the gut compared to when glucose is injected into the veins . This is because when sugar enters the gut, messages are sent from the gut to the pancreas to produce more insulin. These messages are chemicals called peptides. The best known gut peptide controlling insulin is called GLP1 . GLP1 speaks to the pancreas after glucose enters the gut, telling it to produce insulin at the right time. It is now known that in type 2 diabetes, GLP1 levels are too low, which is partly why blood sugar levels go too high after a meal . There are now many medicines that increase GLP1 levels to control post-prandial hyperglycaemia which are therefore good treatments for type 2 diabetes.
Last reviewed: Jul 2022
How Is Insulin Resistance Treated
Since not all factors that contribute to insulin resistance can be treated, such as genetic factors and age, lifestyle modifications are the primary treatment for insulin resistance. Lifestyle modifications include:
- Eating a healthy diet: Your healthcare provider or nutritionist may recommend avoiding eating excessive amounts of carbohydrates and eating less unhealthy fat, sugar, red meats and processed starches. Instead, theyll likely recommend eating a diet of whole foods that includes more vegetables, fruits, whole grains, fish and lean poultry.
- Physical activity: Getting regular amounts of moderate-intensity physical activity helps increase glucose energy usage and improve muscle insulin sensitivity. A single session of moderate-intensity exercise can increase glucose uptake by at least 40%.
- Losing excess weight: Your healthcare provider may recommend trying to lose excess weight to try treating insulin resistance. One study revealed that losing 7% of your excess weight can reduce the onset of Type 2 diabetes by 58%.
Over time, these lifestyle modifications can:
- Increase insulin sensitivity .
- Lower your blood glucose levels.
- Raise HDL cholesterol levels.
You may work with other healthcare providers, such as a nutritionist and endocrinologist, in addition to your regular doctor to come up with an individualized treatment plan that works best for you.
Reprogramming Cells To Produce Insulin
Each cell in the body develops to serve a particular function, but the identity that some cells take on is not always final, as the investigators in the current study note.
Instead, some adult cells are able to adapt and shift and can potentially replace cells with other functions that have died or become damaged.
cells are not terminally differentiated but maintain some plasticity potential even in higher organisms, the researchers note.
Cells might change and adapt as a result of injury or stress to compensate for the loss of other, neighboring cells. However, scientists are still striving to gain a better understanding of how and when this happens, since this process has important potential in regenerative medicine.
In the current study, the researchers were able, for the first time, to uncover some of the key mechanisms that allow cells to switch identity, looking specifically at pancreatic alpha- and beta-cells in a mouse model.
They found that alpha-cells respond to complex signals they receive from neighboring cells in the context of beta-cell loss. Approximately 2 percent of alpha-cells can thus reprogram themselves and start producing insulin.
By using a compound able to influence cell signaling in the pancreas, the researchers could boost the number of insulin-making cells by 5 percent. While this may be a relatively small number, it is a significant first step in learning how to wield the bodys own potential to fight diabetes.
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Effects Of O Sanctum On Insulin Secretion From Perfused Pancreas
LongâEvans rats were anaesthetized with sodium pentobarbital and the pancreas was isolated and perfused at 37 °C according to the method of Giroix et al.. Extract and fractions of O. sanctum were dissolved in KrebsâRinger bicarbonate buffer containing 2.8 or 11.1 mM d-glucose. The perfusate was continuously gassed with a mixture of O2/CO2 . After the first 20-min equilibration period, the composition of the perfusate changed as indicated in Fig. 2 . Effluent samples were stored at â20 °C for insulin assay.
How Is Insulin Controlled
The main actions that insulin has are to allow glucose to enter cells to be used as energy and to maintain the amount of glucose found in the bloodstream within normal levels. The release of insulin is tightly regulated in healthy people in order to balance food intake and the metabolic needs of the body. This is a complex process and other hormones found in the gut and pancreas also contribute to this blood glucose regulation. When we eat food, glucose is absorbed from our gut into the bloodstream, raising blood glucose levels. This rise in blood glucose causes insulin to be released from the pancreas so glucose can move inside the cells and be used. As glucose moves inside the cells, the amount of glucose in the bloodstream returns to normal and insulin release slows down. Proteins in food and other hormones produced by the gut in response to food also stimulate insulin release. Hormones released in times of acute stress, such as adrenaline, stop the release of insulin, leading to higher blood glucose levels to help cope with the stressful event.
Insulin works in tandem with glucagon, another hormone produced by the pancreas. While insulin’s role is to lower blood sugar levels if needed, glucagon’s role is to raise blood sugar levels if they fall too low. Using this system, the body ensures that the blood glucose levels remain within set limits, which allows the body to function properly.
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Researchers Use Zinc To Target Insulin
To treat diabetes directly, rather than manage its symptoms, doctors need a way to get drugs to cells that produce insulin. The key, Stanford researchers report, may be those cells affinity for zinc.
Justin Annes, Tim Horton and colleagues developed a zinc-loving chemical compound that helps deliver drugs that trigger insulin-producing cells in the pancreas , but not others , to replicate .Christine Gray
An insulin injection can manage diabetes symptoms, but actually curing the disease would mean healing cells in the pancreas that produce insulin, a hormone that regulates the amount of sugar in blood.
One promising approach may be to stimulate the regeneration of those cells with drugs. But theres a major obstacle: The growth triggered by the drug is willy-nilly, affecting tissues not just in the pancreas but throughout the body.
Now, a team of Stanford University endocrinologists and chemists has taken a step toward targeting the right cells more precisely, using a property that researchers have long known about but never exploited for treatment: Beta cells, the insulin-producing cells in the pancreas, have a particularly strong taste for zinc.
In a study published online Dec. 6 in Cell Chemical Biology, Stanford researchers used that fact to selectively deliver a drug to beta cells. Justin Annes, MD, PhD, assistant professor of medicine, is the senior author. Graduate student Timothy Horton is the lead author.
Cellular Signaling Transduction Pathways In Regulation Of Insulin Secretion
Several proteins participate in insulin exocytosis. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor plays an essential role in insulin granule membrane fusion. Four SNARE motifs form the extremely stable helical -cell exocytotic core complex. The central part of this complex contains four highly conserved amino acids contributed by the four SNARE motifs: three glutamine , and one arginine residue . In -cells, the fusion of the insulin granules with the plasma membrane involves the assembly of a complex consisting of VAMP-2 on the granule membrane, syntaxin-1a on the plasma membrane, and the membrane-associated protein SNAP-25 . The assembly of this complex can be regulated by other accessory factors to achieve elegant regulation of insulin granule fusion. Tomosyn-1 is such a regulatory factor that can replace VAMP2 in the process of assembly . It is required for granule fusion and/or priming of the granules, but its absence does not influence insulin granule transport and docking .
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Your Pancreas Is A Very Important Six Inch Powerhouse
Your pancreas is a flat, oblong organ about six inches long thats located deep in the upper left-center region of the abdomen, surrounded by the stomach, liver, spleen, gallbladder and small intestine.
The pancreas has two primary functions:
Yeah, exocrine vs endocrine was new to me, too. Who woulda thunk it, but the pancreas functions both as an exocrine and endocrine gland, or organ:
Exocrine glands relate to or denote glands that secrete their products through ducts opening onto an epithelium rather than directly into the bloodstream whereas endocrine glands relate to or denote glands that secrete hormones or other products directly into the blood.
Functioning as an exocrine gland, the pancreas produces and excretes enzymes and digestive juices into the small intestine to break down the proteins, lipids, carbohydrates, and nucleic acids in food after it has left the stomach. Functioning as an endocrine gland, the pancreas produces and secretes the hormones insulin and glucagon to regulate the bodys glucose or blood sugar levels throughout the day, as well as some other hormones.
But before we dive into those specifics, ask yourself if you may have a problem with your pancreas?
Symptoms of pancreatic problems
What Is The Difference Between Glucagon And Insulin
Glucagon and insulin are both important hormones that play essential roles in regulating your blood glucose . Both hormones come from your pancreas alpha cells in your pancreas make and release glucagon, and beta cells in your pancreas make and release insulin.
The difference is in how these hormones contribute to blood sugar regulation. Glucagon increases blood sugar levels, whereas insulin decreases blood sugar levels. If your pancreas doesnt make enough insulin or your body doesnt use it properly, you can have high blood sugar , which leads to diabetes.
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Viii Pharmacologic Modulators Of Insulin Response
There is a plethora of pharmcologic agents designed to target various aspects of glucose metabolism. In this chapter, we provide examples of pharmacologic agents that directly or indirectly modulate insulin response.
A. Incretin mimetics
Diabetes therapeutics have recently utilized the role of incretin hormones for pharmacologic benefit. Due to the desirable effect of GLP-1 on hemoglobin A1c reduction and weight loss , GLP-1 receptor agonists and inhibitors of its degradation via dipeptidyl peptidase-4 inhibitors, have been used to treat type 2 diabetes since 2005.
Short-acting GLP-1 receptor agonists , and long-acting GLP-1 receptor agonists potentiate insulin secretion and reduce gastric motility . Given that GLP-1 receptor agonists potentiate glucose-induced insulin gene transcription, they, alone, do not induce hypoglycemia when used as monotherapy .
DPP-4 inhibitors can significantly increase the peak post-prandial concentration of GLP-1 . Additionally, sitagliptin has been found to potentiate GSIS independently of GLP-1 via islet peptide tyrosine tyrosine .
B. Sulfonylureas
C. Insulin Sensitizers
D. Diazoxide
Diazoxide is a sulfonamide pharmacological agent used in treatment of hyperinsulinism, insulinoma, and hypoglycemia due to overtreatment with sulfonylureas. It works by opening b cell membrane potassium ATP channels, hyperpolarizing the b cells, thus decreasing intracellular calcium concentration and inhibiting insulin secretion .
How Does Insulin Resistance Affect My Body
The development of insulin resistance typically increases insulin production so your body can maintain healthy blood sugar levels. Elevated levels of insulin can result in weight gain, which, in turn, makes insulin resistance worse.
Hyperinsulinemia is also associated with the following conditions:
You dont have to have all four of these features to have metabolic syndrome.
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What Is The Difference Between Insulin Resistance And Diabetes
Anyone can develop insulin resistance temporarily or chronically. Over time, chronic insulin resistance can lead to prediabetes and then Type 2 diabetes if its not treated or able to be treated.
Prediabetes happens when your blood glucose levels are higher than normal, but not high enough to be diagnosed as diabetes. Prediabetes usually occurs in people who already have some insulin resistance.
Prediabetes can lead to Type 2 diabetes , the most common type of diabetes. T2D happens when your pancreas doesnt make enough insulin or your body doesnt use insulin well , resulting in high blood glucose levels.
Type 1 diabetes happens when your bodys immune system attacks and destroys the insulin-producing cells in your pancreas for an unknown reason. T1D is an autoimmune and chronic disease, and people with T1D have to inject synthetic insulin to live and be healthy. While T1D is not caused by insulin resistance, people with T1D can experience levels of insulin resistance in which their cells dont respond well to the insulin they inject.
Gestational diabetes is a temporary form of diabetes that can happen during pregnancy. Its caused by insulin resistance thats due to the hormones the placenta makes. Gestational diabetes goes away once you deliver your baby. Approximately 3% to 8% of all people who are pregnant people in the United States are diagnosed with gestational diabetes.
What Hormone Causes The Pancreas To Release Insulin
Insulin is released by the beta cells in the islets of Langerhans in response to food. Its role is to lower glucose levels in the bloodstream and promote the storage of glucose in fat, muscle, liver and other body tissues. Alpha cells in the islets of Langerhans produce another important hormone, glucagon.
What hormones stimulate insulin?
Insulin secretion by the cells of the islets of Langerhans is primarily regulated by the d-glucose level in the extracellular fluid bathing the cells. Glucagon increases and somatostatin decreases insulin release via paracrine actions. Insulin release is stimulated by GH, cortisol, PRL, and the gonadal steroids.
What stimulates the release of insulin?
Proteins in food and other hormones produced by the gut in response to food also stimulate insulin release. Hormones released in times of acute stress, such as adrenaline, stop the release of insulin, leading to higher blood glucose levels to help cope with the stressful event.
Does protein stimulate insulin release?
Dietary proteins have an insulinotropic effect and thus promote insulin secretion, which indeed leads to enhanced glucose clearance from the blood. In the long term, however, a high dietary protein intake has been associated with an increased risk of type 2 diabetes.
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Vphysiology Of Insulin Secretion In Vivo
Insulin secretionin vivo has also been extensively studied. As predictable from the studies of single beta cells described above, the most important regulators of insulin secretion are circulating nutrients, in particular, glucose. In the fasting state, insulin secretion is maintained at levels that provide sufficient insulin to constrain hepatic glucose release at rates that match glucose utilization and so the plasma glucose concentration is maintained at normal levels of 90 mg/dl . After meal ingestion, glucose concentrations in the circulation rise and stimulate insulin secretion . Increased delivery of insulin into the circulation causes further suppression of hepatic glucose release and increased stimulation of glucose uptake by insulin-sensitive tissues such as muscle to restore normoglycemia. Therefore, the simplest model to describe insulin secretion in vivo would have two components: a constant basal rate of insulin secretion superimposed on which are meal-related increments. Although this model is commonly employed by physicians attempting to replace insulin in patients who secrete insufficient insulin, it is an oversimplification of a very complex dynamic neuroendocrine secretory system.
Juris J. Meier, in, 2016
Producing Too Much Insulin
Excess insulin production occurs when your cells become insensitive to insulin. Think of it this way: insulin knocks on the door of your cells to tell them to let glucose in, but the cells dont answer the door in a timely manner. The pancreas releases more insulin in an effort to get glucose into cells and out of the bloodstream, where too much sugar floating around can damage nerves. A vicious cycle ensues where the pancreas produces more insulin to keep blood sugar balanced. After a while the pancreas can have trouble keeping up with the extra insulin production. Then blood sugar levels rise, increasing the risk of type 2 diabetes.
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When The Blood Glucose Level Goes Up
- Blood sugar rises
- The pancreas detects the rise
- The pancreas pumps out insulin into the blood
- Insulin helps the uptake of glucose into muscles and other cells
- This causes the blood glucose level to fall to its normal set point and
- The pancreas detects the fall and switches off insulin production.
Who Does Insulin Resistance Affect
Insulin resistance can affect anyone you dont have to have diabetes and it can be temporary or chronic. The two main factors that seem to contribute to insulin resistance are excess body fat, especially around your belly, and a lack of physical activity.
People who have prediabetes and Type 2 diabetes usually have some level of insulin resistance. People with Type 1 diabetes can also experience insulin resistance.
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What Happens If I Have Too Much Insulin
If a person accidentally injects more insulin than required, e.g. because they expend more energy or eat less food than they anticipated, cells will take in too much glucose from the blood. This leads to abnormally low blood glucose levels . The body reacts to hypoglycaemia by releasing stored glucose from the liver in an attempt to bring the levels back to normal. Low glucose levels in the blood can make a person feel ill.
The body mounts an initial ‘fight back’ response to hypoglycaemia through a specialised set of of nerves called the sympathetic nervous system. This causes palpitations, sweating, hunger, anxiety, tremor and pale complexion that usually warn the person about the low blood glucose level so this can be treated.
However, if the initial blood glucose level is too low or if it is not treated promptly and continues to drop, the brain will be affected too because it depends almost entirely on glucose as a source of energy to function properly. This can cause dizziness, confusion, fits and even coma in severe cases.
Some drugs used for people with type 2 diabetes, including sulphonylureas and meglitinides , can also stimulate insulin production within the body and can also cause hypoglycaemia. The body responds in the same way as if excess insulin has been given by injection.