IGF-1 Definition

IGF-1 (Insulin-like growth factor-1) or somatomedin C is a peptide (short chain of amino acids) hormone that regulates growth hormone (GH) synthesis and so affects tissue development. It also promotes tissue development without causing growth hormone to be released. This growth factor functions independently of GH when it is produced by an autocrine or paracrine hormone in the liver and particular cells and tissues.

What is IGF-1?

IGF-1 is a hormone proliferation factor which moves from the liver (through the circulatory system) to the brain and single cells by binding to an insulin-like growth factor binding protein (IGFBP). It’s a member of the somatotropic axis, a hormone-based signalling mechanism.

The somatotropic axis is initiated by the secretion of two hormones known as growth hormone-releasing hormone (GHRH) and ghrelin. The pituitary gland is stimulated to increase growth hormone production as a result of these factors. GH interacts with particular receptors once it is generated. When the liver and other less important organs are bound, they are told to create IGF-1.

IGF-1 prompts the pituitary gland to release less growth hormone and the hypothalamus to secrete less GH-releasing hormone when it binds to its own receptor. This feedback mechanism is always working to keep the levels of growth hormone and IGF-1 in check.

The whole somatotropic feedback mechanism is impacted when IGF-1 receptors become less responsive or when IGF-1 is not generated in appropriate numbers. Low levels of IGF-1 may cause major developmental difficulties since it is required for brain and cell growth. Gene mutations or abnormalities in the synthesis of additional somatotropic axis hormones and their receptors may also have a domino effect.

From the time of conception through the 3rd decade of existence, IGF-1 levels are high. From this point on, output gradually declines; the older we become, the less IGF-1 we make. This is paralleled in the synthesis of growth hormones.

However, it is still unclear if higher levels of IGF-1 in old age are beneficial to human health. According to certain research, the greater the level of IGF-1 in the elderly, the greater the incidence of dementia, whereas low levels of IGF-1 lower the risk. In some studies, high IGF-1 levels were associated with an increased chance of cancer, whereas low IGF-1 levels were connected to a relatively high risk of cancer in others. We still have a long way to go.

IGF-1 Hormone Function

The IGF-1 hormone regulates a number of developmental and metabolic activities inside the human body, albeit the majority of these pathways are yet unknown.

Insulin-like growth factor is a pleiotropic hormone, which means that it’s made by a specific gene that also makes other proteins. IGF-1 is produced by a similar gene that also produces insulin as well as relaxin. This gene’s mutations may influence all or any of these hormones, resulting in a variety of physiological and metabolic abnormalities.

Relaxin has a role in both male and female reproduction. Insulin and IGF-1 are essential for our metabolic and physiological development (tissue growth). Insulin-like growth factor and insulin binding proteins and receptors, which were previously considered to have completely different functions, are now known to interact. Because diabetics often have several hormone abnormalities and because decreased insulin production or insulin resistance is the fundamental cause of diabetes, under the phrase insulin protein superfamily, all important components are gathered collectively.

Despite the fact that insulin-like growth factor is more crucial for proliferation than insulin, all are required for glucose control. IGF-1, for instance, stimulates glucose circulation in osteoblasts, the bone-forming cells. IGF-1 is involved in a variety of processes, including our ability to smell, neuron synapses, bone growth and mineralization, cell proliferation, cell differentiation, and the death of cells.

In the Central Nervous System

Both GH and IGF-1 have a role in brain growth, nerve myelination, amyloid clearance (which is crucial in Alzheimer’s disease progression), and anti-inflammatory processes in the central nervous system.

Low GH levels are common in MS patients with high impairment ratings, while low IGF-1 and GH levels are common in Alzheimer’s patients. The less growth hormone we make as we age, the more our neurons deteriorate. The younger we are, the higher our levels of insulin-like growth factor-1 and growth hormone are, as well as the more efficiently our brains function. IGF-1 levels are greater in children with higher IQs. When physical development ceases, IGF-1 aids damaged neurons’ healing at the cellular level.

Cardiovascular Function

IGF-1 and GH are both involved in the development and preservation of the cardiovascular system. They promote vasodilation, which improves blood circulation to areas of the body that need more nutrients and oxygen, or the widening of blood vessels. The progression of atherosclerosis is also slowed by wider blood vessels.

Within the blood vessels, insulin-like growth factor 1 acts like an antioxidant and anti-inflammatory, According to research, When the pituitary gland, which generates GH, is injured, GH levels are low and IGF-1 levels are high in a variety of disorders. Gigantism (also known as acromegaly) is a condition that causes the bones of the hands, feet, and face to become unnaturally large. Cardiovascular issues are more common in those with acromegaly. Excessive bone development causes the huge jaw that is characteristic of acromegaly, as seen here.

In the Kidneys

IGF-1 levels influence the development of capillaries in the kidney glomerulus. Insulin-like growth factor (IGF) improves blood circulation towards the kidneys and glomerular filtration rate (GFR) by directly or indirectly associating with the renin-angiotensin system (RAS).

Polycystic kidney disease has been linked to increased insulin-like growth factor-1 activity, whereas chronic kidney failure is linked to IGF-1 resistance, which occurs when the body generates enough of the polypeptide but is unable to metabolise or utilise it.

Diabetes

Insulin-like growth factor-1 is the complete name of a hormone involved in diabetes. Its relevance is increased by the fact that it is a member of the insulin protein superfamily. Nearly half of the DNA coding of IGF-1 matches that of insulin. IGF-1 levels that are either low or too high are linked to poor glucose sensitivity, an early sign of type II diabetes mellitis.

Insulin and IGF-1 both help cells absorb sugar, lowering blood sugar levels. The quantity of glucose generated in the liver is reduced as a result. On the other hand, growth hormone boosts glucose synthesis. These hormones assist in managing blood sugar levels in healthy people by acting as a feedback mechanism. This feedback mechanism is entirely out of whack when diabetes is present.

When insulin-like growth factor-1 levels are low, men are less prone to developing insulin resistance. Even throughout puberty, girls are generally less insulin sensitive (insulin resistant) than boys. This tendency has been confirmed by several sex-specific growth hormone replacement medications. For the treatment of diabetes, there are no licenced growth factors. A recent study indicates that neither hormone is promising.

In Blood Cells

Hematopoiesis, or the creation of blood cells, occurs inside the bone marrow. White blood cell, red blood cell, and platelet synthesis involve a variety of growth factors. All of these cells start out as hematopoietic stem cells and then develop into progenitor cells before becoming T and B lymphocytes and erythrocytes. All of these phases of development are controlled by growth factors.

Insulin-like growth factor-1 is one of these regulatory factors. IGF-1 receptors are found in osteoblasts, chondrocytes (cartilage-producing cells), and osteocytes. Low levels of insulin-like growth factor-1, which stimulates bone and cartilage development, are linked to osteoporosis. It also reduces cell death and protects these cells from oxidative stress (apoptosis).

IGF-1 is required for growth hormone to enhance osteoblast synthesis. They work together to control bone growth and resorption. When bone development is disrupted, the possibility of aberrant bone development As we’ve witnessed, gigantism, also known as acromegaly, causes excessive bone development. A damaged pituitary gland causes an imbalance in GH and IGF-1, resulting in this condition.

Insulin-like growth factor-1 deficiency may possibly contribute to the progression of acute lymphoblastic leukaemia (ALL). Another element of IGF-1 – its binding proteins – is most likely to blame for this. All children seem to have low IGF-1 levels and a large number of binding proteins. This study is still in its early stages, and there are no explanations as of yet.

Low or high amounts of IGF, which is also generated by cancer cells, may halt or accelerate cancer development. We have not yet discovered a method for treating cancer using insulin-like growth factor.

GH vs IGF-1

IGF-1 production is influenced by the supply of growth hormone as well as the activity of both the pituitary gland and liver. The availability of IGF-1 determines GH production. This codependency is unsurprising given their status as key participants in the somatotropic feedback system.

Growth hormone, generated by the pituitary gland, is responsible for more than just regulating growth. When GH levels are high, it stimulates triglyceride breakdown in the blood and delays lipid absorption in adipocytes (fat cells). Consequently, injectable human growth factor (HGH) is now being investigated as a possible weight loss aid, despite the fact that it is not yet authorised.

It is recognised that elevated HGH levels increase the risk of cardiovascular disease. Therefore, this medication is unlikely to satisfy the FDA’s strict standards. Increased IGF-1 levels as a consequence of elevated GH may also raise the chance of some cancers forming.

Other actions of growth hormone include increasing muscle mass and increasing glucose synthesis in the liver. Growth hormone is also known to have mood-enhancing properties. Low amounts might make people feel fatigued and despondent.

Multiple variables influence GH synthesis and regulation. The amount of growth hormone we make may be reduced or increased depending on stress, diet, and sleep quality.

IGF-1 is largely generated in the liver. It stimulates glucose absorption at the cellular level, lowering rather than raising blood sugar levels (as with GH). Insulin-like growth factor-1 also promotes fatty acid absorption.

Despite its involvement in protein synthesis, it does not seem to have the same impact on muscle mass as growth hormone. Decreased levels of IGF-1, like GH, are linked to low energy and mood.

The U-shaped curves of both hormones indicate how excessively high or low levels are hazardous. It is one of the causes why the results of research on IGF-1 levels are so inconsistent. If you produce insufficient IGF-1 and endure as a consequence, consuming excessive dosages might put you on the other side of the curve, with comparable unfavourable repercussions. The peaks of very hot (too high IGF-1) and much too cool (too low) are undesirable, much as in the fable of Goldilocks and the Three Bears, where just one bowl of porridge is ideal.

The same is true for GH. Neither hormone must be purchased over-the-counter; their use needs periodic blood tests and must be supervised by an endocrinologist.

IGF-1 Testing

The primary purpose of IGF-1 testing is to determine growth hormone levels. Serum (blood circulation) levels of insulin-like growth factor are measured in an insulin-like growth factor test. Although pituitary tumours (which may cause gigantism or acromegaly) sometimes provide odd findings, it is more normal for results to be low. Ted Cassidy (below), who portrayed Lurch in the original Addams Family series, suffered from gigantism as a youngster (which contributed to his huge size) and acromegaly caused by an uncontrollable pituitary gland following puberty.

Growth hormone production is measured using IGF-1 because its daily curve is relatively steadier than the daily fluctuations of growth hormone production. IGF-1 readings, on the other hand, will be unreliable if the liver is destroyed. These values do not match the GH curve precisely, even when the liver is not injured — high GH concentrations only raise IGF-1 levels to a specific threshold. Hepatocytes (liver cells) cannot continue to function at this rate.

Low levels of IGF-1 suggest GH insufficiency or receptor sensitivity. Low levels of GH in children inhibit their development and growth. They may attain normal height if given growth hormone.

As a result of the feedback loop, low levels of GH result in low levels of IGF-1, resulting in a reduction in IGF-1 synthesis in response to reduced pituitary function. Pituitary dysfunction may be induced by inherited genes or triggered by head trauma and inflammation. The pituitary gland may also be affected by infections.

Because the liver and kidneys are the organs that produce the most insulin-like growth factor-1, a low level might suggest a problem with these organs.

Excess GH production is the most prevalent cause of high IGF-1 levels, which are at the other extreme of the U-shaped curve. It is reasonable to expect higher levels throughout puberty as well as pregnancy, considering that both are crucial periods of development and growth. Gestational diabetes is more probable in pregnant women who generate less IGF-1 during their pregnancy.

IGF-1 LR3–Health Supplement or Carcinogen?

IGF-1 LR3 (long arginine 3-IGF-1) is a synthetic variant of IGF-1 that researchers produced to examine the hormone’s activities over extended periods of time. Natural IGF-1 has a short half-life and enjoys interacting with various proteins, which might cause lab-based test findings to vary.

Despite the fact that IGF-1 LR3 is exclusively allowed in laboratories, it has found its way towards the bodybuilding sector. When administered as an intramuscular injection, it is used to enhance skeletal muscle growth and fat loss. Oral supplements are also available. There have been no extensive clinical trials involving humans to determine the safety of either medication. This artificial insulin-like growth factor was never intended to be created or utilised as a dietary supplement.

IGF-1 LR3 is not a human-approved medicine, and its long-term effects are unknown. Natural insulin-like growth factor-1 has a variety of functions, including stimulating cell reproduction and extending cell lifespan. This may render it carcinogenic. Several studies establish a connection between IGF1 and breast, colorectal, and prostate tumors, while others find none. It’s unclear if this holds true for IGF-1 LR3.

Acromegaly

Acromegaly and gigantism may be diagnosed with IGF-1 testing. These words pertain to the identical pituitary gland dysfunction-related condition. Gigantism occurs prior to the fusion of the bone plates of the lengthy bones (femur, tibia, fibula, humerus, radius, ulna, metacarpals of the fingers, and metatarsals of the toes). Following the fusion of these bones, acromegaly develops in adults. The bones of the face, feet, and hands grow in size rather than get longer.

An IGF-1 test and an oral glucose tolerance test are used to diagnose gigantism or acromegaly. A glucose tolerance test involves drinking a sweet beverage and checking blood glucose readings on a frequent basis. This indicates the rapidity of insulin production and the sensitivity of cells to insulin. The production of GH and IGF-1 is usually reduced when blood glucose levels increase.

High blood sugar levels have no effect on GH production in those with gigantism or acromegaly because the pituitary gland cannot function correctly, resulting in elevated GH and IGF-1 levels.

Since they are both members of the insulin protein family, growth hormone as well as blood glucose levels are intricately related. The presence of high insulin-like growth factor-1 and GH, as well as rising blood glucose, is a significant indicator of acromegaly. However, this is not always the case. Stress, eating disorders, thyroid dysfunction, diabetes, puberty, pregnancy, and liver and kidney failure all raise these two hormones.

References

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• Ashpole, NM, Logan, S, et al. (2017). IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan. GeroScience, 39(2), 129–145. https://doi.org/10.1007/s11357-017-9971-0
• Wang, Y, Bikle, DD, Chang, W. (2013). Autocrine and Paracrine Actions of IGF-I Signaling in Skeletal Development. Bone research, 1(3), 249–259. https://doi.org/10.4248/BR201303003
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