Somatostatin is the hormone that controls many other hormones in the body. Because it is available throughout the body, abnormal levels of somatostatin can cause various health problems. Read on to learn more about the many functions, health benefits, side effects, and diseases linked to somatostatin.

Structure and Function

https://www.ncbi.nlm.nih.gov/pubmed/16764934

Two scientists accidentally discovered it when they were dissecting the brain of a sheep.

Somatostatin is a 14 amino acid peptide hormone that is in virtually every organ in the body. It acts as a hormone, a local regulator, and a neurotransmitter.

Somatostatin is produced in the hypothalamus ( the brain region that controls hormone secretion), the gut, and the pancreas (intestinal and pancreatic D cells) [R, R, R].

Somatostatin inhibits the release of hormones by binding to five somatostatin receptors (G-protein coupled receptors sst1 to sst5). Because somatostatin influences most organs and tissues in the body, it is a hormone that rarely deviates from the normal range [R, R].

Excess levels of somatostatin cause very low levels of many other hormones, while low levels of somatostatin cause excess levels of many other hormones [R, R].

  • sst2 and sst5 are located throughout the digestive tract, the pancreas, and the immune system. Most types of synthetic somatostatin bind to these two receptors.
  • sst1, 2, 4, and 5 stop cell growth by activating proteins that suppress tumors and induce cell death (MAPK, tumor suppressor protein, and p21).
  • sst3 triggers cell death by activating the proteins p53 and Bax.

A larger 28 amino acid somatostatin is the precursor to the 14 amino acid peptide. It binds more tightly to receptors and is 10 times stronger than the normal somatostatin in inhibiting growth hormone and insulin secretion [R].

Gut and Pancreatic Function

Somatostatin is released locally in The gut releases somatostatin locally, where it inhibits many gut hormones, and prevents local motor activity. It is found in hormone-secreting cells (endocrine cells) and nerve fibers of the digestive tract [R, R, R].

  • In the stomach, somatostatin inhibits stomach acid and stomach motor functions, slows down stomach emptying, and decreases the perception of fullness [R].
  • In the small intestines, somatostatin inhibits function and blood flow, decreases intestinal fluid secretion, and increases absorption of water and electrolytes into the bloodstream. After consuming a meal, somatostatin levels rise and inhibit glucose and fat absorption [R].
  • In the colon, somatostatin stimulates muscle contractions, increases transit time, and changes colon surface cell (epithelial) function [R].
  • In the pancreas, somatostatin decreases pancreas volume and inhibits release of glucagon and insulin, which are two hormones also produced by the pancreas [R].

Somatostatin increased food consumption with low doses but decreased food consumption with higher doses. Somatostatin may have pain-relieving effects and enhance learning [R].

Gut Hormone Regulation

Nutrients and stomach acid (low pH) are the main stimulants of somatostatin release. Fat and protein elicit a bigger somatostatin response than carbohydrates [R, R].

  • The neurotransmitter acetylcholine stimulates somatostatin release after eating a meal.
  • Gut peptides like gastrin, cholecystokinin, secretin, gastrin-releasing peptide, oxyntomodulin, and glucagon-like peptide also stimulate somatostatin.
  • Substance P, insulin, pancreatic polypeptide, and opioids are potent inhibitors of somatostatin release.

Brain and Spinal Cord Function

Somatostatin-producing neurons and receptors are widely distributed throughout the brain and spinal cord [R]:

  • Hypothalamus – controls body temperature, thirst, hunger, the release of hormone from the pituitary gland, and is involved in sleep and emotion.
  • Pituitary gland – secretes many hormones, including growth hormone, adrenocorticotropic hormone, and thyroid-stimulating hormone.
  • Hippocampus – involved in memory and emotion.
  • Cortex – plays an important role in memory, attention, and consciousness
  • Brainstem – controls heart rate, breathing, sleeping, and eating.
  • Spinal cord – sends messages to and from the brain to the rest of the body, involved in sensation and motor function.

Somatostatin has both inhibitory and excitatory effects on neurotransmitters and hormones [R]:

Brain and Spinal Cord Regulation

Somatostatin is regulated by neurotransmitters and hormones in the brain [R]:

  • Dopamine, acetylcholine, and growth hormone increases somatostatin. GABA and adrenocorticotropic hormone inhibit somatostatin.
  • Neurotensin stimulates somatostatin secretion in the hypothalamus and part of the cortex (neocortex).
  • Vasoactive intestinal peptide inhibits somatostatin secretion in the hypothalamus but stimulates its release from the neocortex.

Immune Function

Somatostatin allows the nervous system, the hormone (endocrine) system, and the immune system to communicate with one another. Somatostatin has a number of effects on immune function [R, R]:

  • Both suppress and stimulates reproduction of one type of white blood cell (lymphocyte).
  • Inhibits the function of other white blood cells (natural killer cells and monocytes).
  • Reduces immune protein (immunoglobulin) production.
  • Lowers the release of inflammatory cytokines (IFN-g), which normally activate an immune response.

Somatostatin receptors are present on white blood cells and tissues of the immune system [R]:

  • Lymph nodes
  • Tonsils
  • Spleen
  • Thymus

Systemic (injection into veins) treatment and local treatment with somatostatin could potentially treat autoimmune diseases and chronic inflammation [R].

Sleep Function

In the elderly, somatostatin disrupted sleep quality by decreasing total sleep time and rapid eye movement sleep (REM) sleep, which is when dreaming usually occurs. Somatostatin also decreased deep sleep (slow wave sleep), during which growth hormone is released and immune function is repaired [R, R].

Bone Function

Somatostatin may inhibit bone growth by locally reducing reproduction and growth of cartilage and bone precursor cells [R].

When injected with insulin, somatostatin has the potential to reduce the calcified cartilage and brittle bones caused by diabetes in a rat model. Somatostatin reduces bone and cartilage growth and development by inhibiting insulin-dependent cell production. It also reduced blood vessel invasion that leads to weak joints and brittle bones [R].

Health Benefits of Somatostatin

Although somatostatin is not often used in medicine, synthetic somatostatin can treat various diseases. Somatostatin analogs have similar molecular structures and mimic its effects. While somatostatin binds to all five somatostatin receptors, the analogs only bind to specific receptors [R].

Commonly used somatostatin analogs include:

  • Octreotide – binds primarily to sst2 and successfully controls over secretion of hormones in patients with hormone-producing tumors [R, R].
  • Pasireotide – binds tightly to sst5 and is used to treat Cushing’s disease and acromegaly [R].
  • Lanreotide – binds tightly to sst2 and less tightly to sst5. It is used to treat acromegaly and tumors in the stomach, intestines, and pancreas [R].

1) Somatostatin Analogs Reduces Tumor Growth

Tumors that produce hormones occur most often in the digestive tract, the pancreas, or the lungs. Hormone-producing tumors are hard to diagnosis due to the nonspecific and variable symptoms. More than 50% of these tumors cannot be surgically removed after diagnosis [R].

Somatostatin analogs can treat symptoms caused by the overproduction of hormones from these tumors. Octreotide can prevent low blood potassium levels, dehydration, and diarrhea in cancer patients with hormone-producing tumors [R].

Injections of octreotide treated 41 patients with hormone-producing tumors in the gut and lungs. Treatment with octreotide led to a 24% response rate in patients and a two-year survival rate of around 76%. Octreotide is an effective treatment for patients with therapy-resistant and progressive cancer [R, R].

Somatostatin analogs also treat non-hormone-producing tumors. Somatostatin stops tumor growth by inhibiting the release of growth hormone and preventing the formation of new blood vessels in tumors [R].

2) Somatostatin Analogs Helps Treat Acromegaly

Excess growth hormone from pituitary gland tumors causes acromegaly. Symptoms include enlargement of the face, hands, and feet. Somatostatin analogs are used when surgery is ineffective in controlling the disease [R].

In a study (DB-RCT), the analogs pasireotide and octreotide significantly reduced tumor size in 358 patients with acromegaly [R].

Somatostatin stops tumor cell growth by activating pathways that prevent cells from dividing (p21 and p27). Somatostatin also reduces symptoms associated with the disease, like heart, sleep, and insulin dysfunction [R, R].

3) Somatostatin Analogs Help Treat Cushing’s Disease and Cushing’s Syndrome

Cushing’s disease is caused by pituitary tumors that produce adrenocorticotropic hormone (ACTH). High levels of ACTH lead to high levels of cortisol, which can damage many tissues and organs in the body [R, R].

Pasireotide targets pituitary tumors and reduces cortisol levels, which lowers body weight, blood pressure, and cholesterol levels [R, R].

Although pasireotide is effective in treating Cushing’s disease, it can cause high blood sugar (by inhibiting glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide) [R].

Cushing’s disease causes Cushing’s syndrome if the body has high levels of cortisol for too long. Cushing’s syndrome symptoms include obesity, thin skin, short stature, high blood pressure, anxiety, depression, bruising, glucose intolerance, and weakness [R].

In 38 patients, octreotide temporarily suppressed cortisol secretion in ACTH-independent Cushing’s syndrome but was not effective for other forms of Cushing’s syndrome [R].

4) Somatostatin Helps Treat Diabetes

Somatostatin is produced in the pancreas (islet D cells) and locally inhibits insulin and glucagon. Insulin reduces blood sugar levels, while glucagon increases blood sugar levels [R].

Somatostatin and insulin helped control excess blood sugar more effectively than insulin alone in 10 diabetic patients [R].

Somatostatin inhibits glucagon and growth hormone, which prevents an increase in blood sugar. It also reduces high blood sugar after consuming food by inhibiting carbohydrate absorption in the digestive tract [R, R, R].

Although somatostatin can treat diabetes, the effects of somatostatin only last for half an hour. Blood sugar can also be precisely controlled with insulin delivery devices [R].

5) Somatostatin Analogs Treat Polycystic Kidney and Liver Disease

In a study (B-RCT) of 39 patients with polycystic kidney disease, octreotide slowed kidney volume growth, which reduced cyst volume. Kidney volume growth was 50% slower in the experimental group than the control group. Octreotide also reduced blood pressure and body weight [R].

In a study (DB-RCT) of 42 patients with the severe polycystic liver disease resulting from polycystic kidney or liver disease, octreotide slowed down the progressive increase in liver and kidney volume [R].

Octreotide inhibits fluid secretion and slows down cyst growth (via inhibition of cAMP production in kidney cells and collecting ducts) [R].

6) Somatostatin Helps Treats Ulcers

Somatostatin helped treat stomach ulcer bleeding in 43 patients (DB-RCT). When the stomach becomes too acidic, blood becomes thinner and does not clot properly when bleeding occurs. Somatostatin stops bleeding by reducing stomach acid secretion and blood flow to the stomach [R].

Low somatostatin levels are associated with ulcers. In 28 patients with intestinal ulcers, the suppression of somatostatin inhibited stomach acid function. After successfully treating the ulcers, somatostatin levels increased significantly [R].

7) Somatostatin Analogs Help Treat Arthritis

In a pilot study, scientists treated 10 arthritis patients with octreotide for three months. The somatostatin analog reduced pain and the number of swollen joints in weeks 8 to 10 but had less effect by week 12 [R].

Octreotide and pasireotide reduced joint swelling and pain in a mouse model of arthritis. Both octreotide and pasireotide reduced pain and inflammation by binding to sst2, one of the five somatostatin receptors [R].

8) Somatostatin Analogs Relieve Diarrhea Caused by Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) patients have overly sensitive intestines. Octreotide reduced discomfort and the feeling of fullness in the large intestines in 8 diarrhea-prone IBS patients [R].

Analogs like octreotide prevent diarrhea by slowing gut transit time, decreasing abnormal fluid secretion into the intestines, and increasing the absorption of water and electrolytes into the bloodstream. Octreotide increases the threshold for intestinal discomfort by inhibiting the release of serotonin from stomach glands [R, R].

9) Somatostatin Aids in the Treatment of Fistulas

Fistulas are abnormal connections between blood vessels, intestines, or other hollow organs. Gut fistulas are the most common cause of severe intestinal failure [R].

In 40 post-surgical patients, direct infusion of somatostatin into fistulas and nutrients into the gut significantly decreased fistula closure time. Somatostatin inhibited the effect of gut hormones and decreased gut muscle contractions, while nutrient infusion prevented nutrient imbalance [R].

Somatostatin and its analogs decreased fistula closure time in 33 patients. Although results were not statistically significant, somatostatin helped fix fluid, electrolyte and protein imbalances caused by fistulas [R].

10) Somatostatin May Treat Pancreatic Diseases

Pancreatitis is the severe inflammation of the pancreas. Acute pancreatitis is caused by digestive enzymes damaging pancreatic tissue, whereas chronic pancreatitis is pancreatic failure commonly resulting from alcoholism [R].

Somatostatin and octreotide reduced the death rate for acute pancreatitis and relieved pain for chronic pancreatitis in multiple clinical trials. Octreotide reduces inflammation in the pancreas by inhibiting cells and pathways (intestinal mucosal mast cells and TLR4NF-kB cytokine pathway) that produce an inflammatory immune response [R, R].

However, octreotide did not stop progression or reduce pain in a study (RCT) of 302 patients with chronic pancreatitis. The use of somatostatin analogs to treat pancreatitis is controversial and scientific studies yield mixed results [R].

11) Somatostatin Analogs May Treat Obesity

In another study with 39 healthy participants (DB-RCT), octreotide slowed stomach emptying and increased stomach volume, but also decreased feelings of fullness after eating a meal [R].

Somatostatin analogs suppress insulin secretion and stop weight gain. Hypothalamic obesity results from tumors in the hypothalamus, a brain region known from controlling hormones, weight, and body temperature [R, R].

In a study (DB-RCT) of 18 children with hypothalamic obesity, octreotide suppressed insulin secretion, which stabilized their weight and body mass index [R, R].

Side Effects of Somatostatin Analogs

Common side effects include [R, R]:

  • Stomach discomfort
  • Loss of appetite
  • Diarrhea
  • Gas
  • Nausea
  • Vomiting
  • Pain
  • Fatigue
  • Headache
  • Dizziness
  • Excess fat in the stools
  • Gallstones

Some analogs like pasireotide and octreotide can cause high blood sugar. Long-term use of octreotide can also result in growth hormone deficiency, which can cause [R, R]:

  • Changes in body composition – excessive body fat and muscle wasting
  • Decreased muscle strength and exercise capacity
  • Increased risk of heart disease
  • Reduced psychological well-being and quality of life

Diseases Linked to High Levels of Somatostatin

  • Somatostatin-producing tumors (Somatostatinomas) [R, R]
  • Brain and Spinal Cord tumors [R, R]
  • Huntington’s Disease [R, R, R]
  • Spinal Cord Disease [R, R]
  • Intervertebral Disc Disease [R, R]
  • Post-Traumatic Stress Disorder [R]
  • Anorexia [R]
  • Irritable Bowel Syndrome [R]
  • Gallstones [R]

Diseases Linked to Low Levels of Somatostatin

 

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