Helicobacter pylori

Helicobacter pylori

The cause of stomach ulcers had long been attributed to stress, spicy foods, smoking, or other lifestyle habits.[1]

Conventional thinking was that no bacterium could live within the acidic environment of the stomach.

It was not until the early 1980's when the bacteria, Helicobacter pylori (H. pylori) was discovered in the stomachs of patients with gastritis and stomach ulcers that conventional thinking began to change...

... Began to change ... as in, the 'H. pylori - ulcer' connection being proposed by Dr. Barry Marshall and Dr. Robin Warren in the early 80's was initially met with strong resistance from colleagues adhering to the accepted theories of the day.

Unable to gain access to suitable test subjects (H. pylori affects only primates), Marshall decided to take matters into his own hands by drinking a solution H. pylori from the gut of an ailing patient. Shortly thereafter, he began to develop symptoms of gastritis, the precursor to an ulcer. Taking a biopsy from his own gut (as one does), he was able to culture H. pylori and show the bacteria to be the underlying cause of ulcers.[16]

In recognition of their discovery, Dr. Barry Marshall and Dr. Robin Warren were awarded the 2005 Nobel Prize in Physiology or Medicine.[12][13][14][15]

• It is estimated that at least half the world's population is infected by the H. pylori bacterium, making it the most widespread infection in the world.[4]

• Considering that statistic, it is indeed fortunate that up to 85% of people infected with H. pylori never experience symptoms or complications.[5]

• On another positive note, the overall frequency of H. pylori infection appears to be on the decline.[2][6]

• Most frequently acquired in early childhood,[2] H. pylori is contagious, although the exact route of transmission is not known.[8][9] 

• It is believed H. pylori may be transmitted person-to-person via the oral-oral or fecal-oral route; oral transmission may also occur through the ingestion of waste-tainted water.[10][11]

COMPLICATIONS ASSOCIATED WITH H. PYLORI INFECTION: 

ULCERS

A benign gastric ulcer of a gastrectomy 
specimen.

A natural mucous barrier exists on the lining of the stomach to protect against its strong digestive acids. 

There is normally a balance between the amount of acid produced by the stomach and the mucous defense barrier.[1][2][3]

H. pylori can damage the protective lining of the stomach and small intestine, and disrupt this balance, allowing stomach acid to create an open sore (ulcer).

Individuals infected with H. pylori have a 10 to 20% lifetime risk of developing peptic ulcers.[2][30][31][34]

INFLAMMATION OF THE STOMACH LINING

By the same action as described above, H. pylori infection can cause inflammation of the stomach lining (gastritis). This may develop into an ulcer.[31]

CANCER

Endoscopic image of gastric ulcer, biopsy proven
to be gastric cancer.

In 1994, the International Agency for Research on Cancer classified H. pylori as a carcinogen, or cancer-causing agent, in humans.[34]

Infection with H. pylori is the primary identified cause of non-cardia gastric cancer (cancer found in all other areas of the stomach other than the top portion).[35-43]

A meta-analysis[33] conducted in 2009 concluded the eradication of H. pylori reduces gastric cancer risk in previously infected individuals. The analysis suggested the continued presence of H. pylori constitutes a relative risk factor of 65% for gastric cancers; in terms of absolute risk, the increase was from 1.1% to 1.7%.[2][31][32]

Although it is not known for certain how H. pylori infection increases the risk of non-cardia gastric cancer, some researchers speculate that the long-term presence of an inflammatory response predisposes cells in the stomach lining to become cancerous.[40][41]

Long-term follow-up of data from a randomized clinical trial carried out in Shandong, China—an area where rates of gastric cancer are very high—found that short-term treatment with antibiotics to eradicate H. pylori reduced the incidence of gastric cancer.

During a nearly 15-year period after treatment, gastric cancer incidence was reduced by almost 40%.[42]

When the results of this trial were pooled with those of several smaller trials examining the effects of H. pylori eradication on incidence of gastric cancer, a similar reduction was seen.[42]

SYMPTOMS   

Acute infection may appear as an acute gastritis (inflammation of the stomach lining) with abdominal pain or nausea.[17]

Where this develops into chronic gastritis, the symptoms may include stomach pains, nausea, bloating, belching, and sometimes vomiting or black stool.[18][19]


DIAGNOSIS[20][21]

H. pylori can be detected via:

• A breath test
• A stool antigen test
• A blood test to detect the presence of H. pylori antibodies 
• If a biopsy sample of the stomach’s lining has been taken during gastroscopy, it can be tested for H. pylori.

Immunohistochemical detection of H. pylori in
gastric biopsy

TREATMENT

• H. pylori infections are usually treated with two varieties of antibiotics at once, to help prevent the bacteria from developing a resistance to one particular antibiotic; as well as an acid-suppressing drug, to help the stomach lining heal.[1]

• Despite efforts to prevent resistance, it is perhaps not entirely surprising to hear that an increasing number of infected individuals are being found to harbor antibiotic-resistant bacteria.[7][22]

• This results in initial treatment failure and requires additional rounds of antibiotic therapy or alternative strategies.[23][24][25] 

• Supplementing diets with yogurt containing Lactobacillus and Bifidobacterium has improved the rates of eradication of H. pylori in humans.[26]

• The substance sulforaphane, which occurs naturally in broccoli and  cauliflower, has also been proposed as a treatment.[27][28][29] 

GENOME

• H. pylori is believed to have migrated out of Africa along with its human hosts around 60,000 years ago.[50][51]

• There is a great deal of diversity among the various strains of H. pylori. The genomes of three have been completely sequenced.[43-47]

A 'PATHOGENICITY ISLAND' IS THE NAME GIVEN TO A COMMON GENE SEQUENCE BELIEVED TO BE RESPONSIBLE FOR PATHOGENESIS

• The Cag PATHOGENICITY ISLAND (cag PAI) is usually absent from H. pylori strains isolated from asymptomatic human carriers of the bacteria.[48]

• About 50–70% of H. pylori strains in Western countries carry the cag PAI.[49]

• Western patients infected with strains carrying the cag PAI have been shown to have a stronger inflammatory response in the stomach and are at a greater risk of developing peptic ulcers or stomach cancer than those infected with strains lacking the island.[2]

***

FIN

REFERENCES:

[1] http://www.mayoclinic.org/diseases-conditions/h-pylori/basics/definition/con-20030903
[2] Kusters JG, van Vliet AH, Kuipers EJ (July 2006). "Pathogenesis ofHelicobacter pylori Infection". Clin Microbiol Rev 19 (3): 449–90.doi:10.1128/CMR.00054-05. PMC 1539101. PMID 16847081.
[3] Amieva MR, El-Omar EM (January 2008). "Host-bacterial interactions in Helicobacter pylori infection". Gastroenterology 134 (1): 306–23. doi:10.1053/j.gastro.2007.11.009.PMID 18166359.
[4] Pounder RE, Ng D (1995). "The prevalence of Helicobacter pylori infection in different countries". Aliment. Pharmacol. Ther. 9 (Suppl 2): 33–9. PMID 8547526.
[5] Bytzer P, Dahlerup JF, Eriksen JR, Jarbøl DE, Rosenstock S, Wildt S (April 2011)."Diagnosis and treatment of Helicobacter pylori infection". Dan Med Bull 58 (4): C4271.PMID 21466771.
[6] Malaty HM (2007). "Epidemiology of Helicobacter pylori infection". Best Pract Res Clin Gastroenterol 21 (2): 205–14. doi:10.1016/j.bpg.2006.10.005. PMID 17382273.
[7] Mégraud F (September 2004). "H pylori antibiotic resistance: prevalence, importance, and advances in testing". Gut 53 (9): 1374–84. doi:10.1136/gut.2003.022111.PMC 1774187. PMID 15306603.
[8] Mégraud F (1995). "Transmission of Helicobacter pylori: faecal–oral versus oral–oral route". Aliment. Pharmacol. Ther. 9 (Suppl 2): 85–91. PMID 8547533.
[9] Cave DR (May 1996). "Transmission and epidemiology of Helicobacter pylori". Am. J. Med. 100 (5A): 12S–17S; discussion 17S–18S. PMID 8644777.
[10] Brown LM (2000). "Helicobacter pylori: epidemiology and routes of transmission". Epidemiol Rev 22 (2): 283–97.doi:10.1093/oxfordjournals.epirev.a018040. PMID 11218379.
[11] Delport W, van der Merwe SW (2007). "The transmission of Helicobacter pylori: the effects of analysis method and study population on inference". Best Pract Res Clin Gastroenterol 21 (2): 215–36. doi:10.1016/j.bpg.2006.10.001. PMID 17382274.
[12] http://www.webmd.com/digestive-disorders/h-pylori-helicobacter-pylori?
[13] "The Nobel Prize in Physiology or Medicine 2005".
[14] Atwood IV KC (2004). "Bacteria, Ulcers, and Ostracism? H. pylori and the making of a myth"
[15] "Helicobacter pylori in peptic ulcer disease". NIH Consensus Statement Online Jan 7–9;12(1):1–23.
[16] http://discovermagazine.com/2010/mar/07-dr-drank-broth-gave-ulcer-solved-medical-mystery.
[17] Butcher, Graham P. (2003). Gastroenterology: An Illustrated Colour Text. Elsevier Health Sciences. p. 25. ISBN 0-443-06215-3.
[18] Butcher 2003, pp. 24–5
[19] Ryan, Kenneth (2010). Sherris Medical Microbiology. McGraw-Hill. pp. 573, 576.ISBN 978-0-07-160402-4.
[20] http://www.webmd.com/digestive-disorders/h-pylori-helicobacter-pylori?
[21] http://www.patient.co.uk/health/helicobacter-pylori-and-stomach-pain
[22] http://en.wikipedia.org/wiki/Helicobacter_pylori
[23] Stenström B, Mendis A, Marshall B (August 2008). "Helicobacter pylori—The latest in diagnosis and treatment". Aust Fam Physician 37 (8): 608–12. PMID 18704207.
[24] Fischbach L, Evans EL (August 2007). "Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori".Aliment. Pharmacol. Ther. 26 (3): 343–57. doi:10.1111/j.1365-2036.2007.03386.x.PMID 17635369.
[25] Graham DY, Shiotani A (June 2008). "Newer concepts regarding resistance in the treatment Helicobacter pylori infections". Nat Clin Pract Gastroenterol Hepatol 5 (6): 321–31. doi:10.1038/ncpgasthep1138. PMC 2841357. PMID 18446147.
[26] Wang KY, Li SN, Liu CS et al. (September 2004). "Effects of ingesting Lactobacillus- and Bifidobacterium-containing yogurt in subjects with colonized Helicobacter pylori". The American Journal of Clinical Nutrition 80 (3): 737–41. PMID 15321816.
[27] J. K. Moon, J. R. Kim et al: Analysis and anti-Helicobacter activity of sulforaphane and related compounds present in broccoli (Brassica oleracea L.) sprouts. In: Journal of Agricultural and Food Chemistry. Volume 58, Number 11, June 2010, pp 6672–6677,ISSN 1520-5118. doi:10.1021/jf1003573. PMID 20459098.
[28] J. W. Fahey, X. Haristoy et al: Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. In: PNAS. Volume 99, Number 11, May 2002, pp 7610–7615, ISSN 0027-8424. doi:10.1073/pnas.112203099. PMID 12032331. PMC 124299.
[29] X. Haristoy, K. Angioi-Duprez u. a.: Efficacy of sulforaphane in eradicating Helicobacter pylori in human gastric xenografts implanted in nude mice. In: Antimicrobial agents and chemotherapy. Volume 47, Number 12, December 2003, pp 3982–3984, ISSN 0066-4804. PMID 14638516. PMC 296232.
[30] http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/peptic-ulcer/Pages/overview.aspx
[31] http://www.patient.co.uk/health/helicobacter-pylori-and-stomach-pain
[32] Fuccio, L; Zagari, RM; Eusebi, LH; Laterza, L; Cennamo, V; Ceroni, L; Grilli, D; Bazzoli, F (2009). "Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer?". Ann Intern Med 151 (2): 121–8. doi:10.7326/0003-4819-151-2-200907210-00009. PMID 19620164.
[33] Greenland S, O' Rourke K: Meta-Analysis. Page 652 in Modern Epidemiology, 3rd ed. Edited by Rothman KJ, Greenland S, Lash T. Lippincott Williams and Wilkins; 2008.
[34] http://www.cancer.gov/cancertopics/factsheet/Risk/h-pylori-cancer
[35] Forman D, Burley VJ. Gastric cancer: Global pattern of the disease and an overview of environmental risk factors. Best Practice & Research Clinical Gastroenterology 2006; 20(4):633–649.
[36] Brenner H, Rothenbacher D, Arndt V. Epidemiology of stomach cancer. Methods in Molecular Biology 2009; 472:467–477.
[37] Atherton JC. The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases. Annual Review of Pathology 2006; 1:63–96.
[38] Kusters JG, van Vliet AH, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clinical Microbiology Reviews 2006; 19(3):449–490
[39] Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: A combined analysis of 12 case control studies nested within prospective cohorts. Gut 2001; 49(3):347–353.
[40] Parsonnet J, Friedman GD, Vandersteen DP, et al. Helicobacter pylori infection and the risk of gastric carcinoma. New England Journal of Medicine 1991; 325(16):1127–1131.
[41] Huang JQ, Sridhar S, Chen Y, Hunt RH. Meta-analysis of the relationship between Helicobacter pylori seropositivity and. Gastroenterology 1998; 114(6):1169–1179.
[42] Eslick GD, Lim LL, Byles JE, Xia HH, Talley NJ. Association of Helicobacter pylori infection with gastric carcinoma: A meta-analysis. American Journal of Gastroenterology 1999; 94(9):2373–2379.
[43] Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. New England Journal of Medicine 2001; 345(11):784–789.
[44] Parsonnet, J, Hansen S, Rodriguez L, et al. Helicobacter pylori infection and gastric lymphoma.New England Journal of Medicine 1994; 330(18):1267–1271.
[45] Sagaert X, Van Cutsem E, De Hertogh G, Geboes K, Tousseyn T. Gastric MALT lymphoma: A model of chronic inflammation-induced tumor development. Nature Reviews Gastroenterology & Hepatology 2010; 7(6):336–346.
[46] Ma JL, Zhang L, Brown LM, et al. Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality. Journal of the National Cancer Institute 2012; 104(6):488-492.
[47] Tomb JF, White O, Kerlavage AR et al. (August 1997). "The complete genome sequence of the gastric pathogen Helicobacter pylori". Nature 388 (6642): 539–47.doi:10.1038/41483. PMID 9252185.
[48] "Genome information for the H. pylori 26695 and J99 strains". Institut Pasteur. 2002.
[49] "Helicobacter pylori 26695, complete genome". National Center for Biotechnology Information.
[50] "Helicobacter pylori J99, complete genome". National Center for Biotechnology Information.
[51] Oh JD, Kling-Bäckhed H, Giannakis M et al. (June 2006). "The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: Evolution during disease progression". Proc Natl Acad Sci U.S.A. 103 (26): 9999–10004.doi:10.1073/pnas.0603784103. PMC 1480403. PMID 16788065.
[52] Baldwin DN, Shepherd B, Kraemer P et al. (February 2007). "Identification ofHelicobacter pylori Genes That Contribute to Stomach Colonization". Infect Immun 75(2): 1005–16. doi:10.1128/IAI.01176-06. PMC 1828534. PMID 17101654.
[53] Peek RM, Crabtree JE (January 2006). "Helicobacter infection and gastric neoplasia". J. Pathol. 208 (2): 233–48. doi:10.1002/path.1868. PMID 16362989.
[54] Correa P, Piazuelo MB (January 2012). "Evolutionary History of the Helicobacter pyloriGenome: Implications for Gastric Carcinogenesis". Gut Liver 6 (1): 21–8.doi:10.5009/gnl.2012.6.1.21. PMC 3286735. PMID 22375167.
[55] Linz B, Balloux F, Moodley Y et al. (February 2007). "An African origin for the intimate association between humans and Helicobacter pylori". Nature 445 (7130): 915–8.doi:10.1038/nature05562. PMC 1847463. PMID 17287725.

IMAGE CREDITS

"EMpylori" by Yutaka Tsutsumi, M.D.Professor Department of PathologyFujita Health University School of Medicine - Yutaka Tsutsumi, M.D.Professor Department of Pathology Fujita Health University School of Medicinehttp://info.fujita-hu.ac.jp/~tsutsumi/photo/photo002-6.htmhttp://info.fujita-hu.ac.jp/~tsutsumi/image/002/2-6.jpg. Licensed under Copyrighted free use via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:EMpylori.jpg#mediaviewer/File:EMpylori.jpg

"Ulcer-causing Bacterium (H.Pylori) Crossing Mucus Layer of Stomach" by Illustration Credit: Zina Deretsky, National Science Foundation - NSF Flickr photostream, http://www.flickr.com/photos/nsf_beta/4822021538/in/set-72157621768317570. Licensed under Public Domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Ulcer-causing_Bacterium_(H.Pylori)_Crossing_Mucus_Layer_of_Stomach.jpg#mediaviewer/File:Ulcer-causing_Bacterium_(H.Pylori)_Crossing_Mucus_Layer_of_Stomach.jpg

"Benign gastric ulcer 1" by Ed Uthman, MD - http://web2.airmail.net/uthman/specimens/index.html. Licensed under Public Domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Benign_gastric_ulcer_1.jpg#mediaviewer/File:Benign_gastric_ulcer_1.jpg

"Gastric ulcer 3" by Original uploader was Samir (The Scope) at en.wikipedia - Originally from en.wikipedia; description page is/was here.. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Gastric_ulcer_3.jpg#mediaviewer/File:Gastric_ulcer_3.jpg

"Immunohistochemical detection of Helicobacter (1) histopatholgy" by User:KGH - User:KGH. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Immunohistochemical_detection_of_Helicobacter_(1)_histopatholgy.jpg#mediaviewer/File:Immunohistochemical_detection_of_Helicobacter_(1)_histopatholgy.jpg

Insulin

DIET  fads and their fleeting results aside, I sometimes think if we could just pause before tucking our forks into that enormous slice of chocolate cake and envision the physiological effects it is about to have on our bodies, we might, if not put our forks down, at least be more inclined to pace ourselves a bit. 

The hormone insulin is synthesized in the pancreas

within the β-cells of the islets of Langerhans.[1]

(Pancreatic islet on diagram)

By physiological effects, I am referring to the demands our increasingly high sugar diets are placing on the vital ability of pancreatic cells to regulate blood glucose levels through the production and release of insulin.

Although glucose is essential to our survival (which is why it makes our brains so hap-hap-happy!) its over-consumption can have negative consequences when the demands it places on our bodies surpasses the ability to meet those demands. 

I am not a proponent of eliminating certain foods from our diet completely. As with most things in life, moderation is key. My own experience has taught me that the second I tell myself I cannot have something, the value my brain places on that item increases a million fold. 

That said, I have also learned that we can train-trick-reprogram our brains into feeling satisfied by more healthy eating patterns and options; to the point where the time may come when we can look at an item we would have previously devoured and quite easily either pace ourselves, or, even better, turn away and reach instead for a more healthy alternative. 

INSULIN

The strong homology seen in the insulin sequence of diverse species suggests that it has been conserved across much of animal evolutionary history.[1][2][3]

Bovine insulin differs from human insulin in only three amino acids.[1]

Porcine insulin differs from human insulin in only one amino acid.[1]

DIRECT & INDIRECT REGULATORY EFFECTS OF INSULIN ON CELLS [1]

Insulin regulates ...

• The cellular intake of glucose in muscle and adipose tissue.
• The storage of glucose in liver and muscle cells in the form of glycogen. When insulin is low, liver cells convert glycogen to glucose and excrete it into the blood. 
• The formation of triglycerides from fatty acid esters in adipose tissue. 
• The cellular absorption of circulating amino acids and potassium.
• Insulin decreases the production of glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids.[4]
• Insulin increases arterial blood flow.
• Insulin decreases renal sodium excretion.[1][5]
• Insulin influences cognition. Once insulin enters the human brain, it enhances learning and memory, and benefits verbal memory in particular.[1][6][7]
• Insulin has also been shown to be produced inside the neurons of the brain, and reduced insulin levels has been linked to Alzheimer's disease.[1][8][9][10]

EFFECT OF INSULIN ON GLUCOSE UPTAKE & METABOLISM.[1] 

(1) Insulin binds to its receptor.

(2) Which starts many protein activation cascades. These include:

(3) Translocation of Glut-4 transporter to the plasma membrane and influx of glucose.

(4) GLYCOGEN synthesis - stored form of energy.

(5) GLYCOLYSIS -  usable energy. 

(6) Formation of TRIGLYCERIDES - stored form of energy. 

HYPERGLYCEMIA & KETOACIDOSIS[11][21]

• Hyperglycemia, or high blood sugar is a condition in which an excessive amount of glucose circulates in the blood plasma.

• This is generally a glucose level higher than 11.1 mmol/l.

• If untreated, hyperglycemia, can result in ketoacidosis (diabetic coma).

• Ketoacidosis develops in the absence of sufficient levels of insulin. Without insulin's regulatory presence, glucose cannot be converted into usable energy. As a result, the body breaks down fats to use for energy.

• This process generates waste products called ketones.

• When these ketones cannot be efficiently eliminated (in the urine), they build up in the blood; and this, can lead to ketoacidosis.

HYPOGLYCEMIA[1]

• Low blood glucose level is known as hypoglycemia.

• As neurons depend solely upon glucose for energy, low blood glucose can impair the normal functioning of the central nervous system.

• Dizziness, speech problems, and loss of consciousness can result; the latter also referred to as hypoglycemic coma or insulin shock.

• Intentional overdoses have been reported, but most insulin shocks appear to be due to errors in dosage of insulin or other unanticipated factors like inadequate diet coupled with over-exertion.

DIABETES

When control of insulin levels fails, diabetes mellitus can result.

TYPE 1 DIABETES is characterized by the loss of insulin-producing β-cells in the pancreas.[1][12][13]

• This type can be further classified as either immune-mediated or triggered by unknown or environmental factors.

• The majority of cases are of the immune-mediated class, in which a T-cell-mediated autoimmune attack leads to the loss of β-cells and thus insulin.[14]

• It can be accompanied by irregular and unpredictable hyperglycemia and sometimes with serious hypoglycemia.[22]

• It is partly inherited, with multiple genes believed to be of influence.[15][22]

• However, genes alone do not determine disease state. This is exemplified in identical twins; as when one twin has type 1 diabetes, the other gets the disease at most, only half the time.[15]

TYPE 2 DIABETES is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion.[16] 

• About 90% of people with diabetes have type 2 diabetes.[13]

• The predominant abnormality at the onset of the condition is reduced insulin sensitivity. At this stage, hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver.[22]

• A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity, lack of physical activity, poor diet, and stress.[17]

• Excess body fat is associated with 30% of cases in those of Chinese and Japanese descent, 60–80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders.[16] 

• Consumption of sugar-sweetened drinks in excess is associated with an increased risk.[18][19] 

• The type of fats in the diet is also important, with saturated fats and trans fatty acids increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk.[20]

DIABETES RELATED COMPLICATIONS CAN INCLUDE: chronic kidney disease, erectile dysfunction, nerve damage, eye disease that can lead to blindness, heart attack, stroke, and non-traumatic lower limb amputation.[13]

Insulin is usually taken as subcutaneous injections.[1]

Oral administration of insulin is precluded by its digestion in the gastrointestinal tract.[1]

Biosynthetic human insulin for large scale clinical use is produced in either yeast or E. coli using recombinant DNA technology.[1][23][24] 

Researchers have also succeeded in introducing the gene for human insulin into safflower plants as another potential means of its production.[1][25][26]

**Notably absent from this entry on insulin are the accomplishments of, Banting, Best, Sanger, Langerhans, and Paulescu, to name a few. Scientists to whom we owe a debt of gratitude for the countless lives saved as a result of their tireless efforts. Mais, si vous voulez, you may click on this LINK for a timeline of insulin’s discovery and initial medical applications.

***

FIN

RELATED LINKS FROM MY NEWS FEED:

February 6, 2015  New Scientist    Both Cause and Cure for Diabetes Could be Your Gut

Jan 21, 2015   New Scientist    Cunning Fish Drug Snails With Insulin Then Eat Them

January 20, 2015  Popular Science   Stick-on Tattoo Measures Blood Sugar Without Needles

REFERENCES

[1] http://en.wikipedia.org/wiki/Insulin
[2] Le Roith, D.; Shiloach, J.; Heffron, R.; Rubinovitz, C.; Tanenbaum, R.; Roth, J. (1985). "Insulin-related material in microbes: similarities and differences from mammalian insulins".Can. J. Biochem. Cell Biol 63: 839–849. doi:10.1139/o85-106.
[3] Alzira Martins Ferreira de Souza, Jorge A. López (2004). Insulin or insulin-like studies on unicellular organisms: a review. Braz. arch. biol. technol. vol.47 no.6 Curitiba Nov. 2004.
[4] http://en.wikipedia.org/wiki/Gluconeogenesis
[5] Gupta AK, Clark RV, Kirchner KA (1992). "Effects of insulin on renal sodium excretion".Hypertension 19 (1 Suppl): 178–182. doi:10.1161/01.HYP.19.1_Suppl.I78.PMID 1730458.
[6] Benedict C, Hallschmid M, Hatke A, Schultes B, Fehm HL, Born J, Kern W. (November 2004). "Intranasal insulin improves memory in humans". Psychoneuroendocrinology 29 (10): 1326–34. doi:10.1016/j.psyneuen.2004.04.003. PMID 15288712.
[7] Benedict C, Brede S, Schiöth HB, Lehnert H, Schultes B, Born J, Hallschmid M. (2010)."Intranasal insulin enhances postprandial thermogenesis and lowers postprandial serum insulin levels in healthy men". Diabetes 60 (1): 114–118. doi:10.2337/db10-0329.PMC 3012162. PMID 20876713 [Epub'd ahead of print]
[8] Gustin N (2005-03-07). "Researchers discover link between insulin and Alzheimer's".EurekAlert!. American Association for the Advancement of Science.
[9] de la Monte SM, Wands JR (February 2005). "Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer's disease". J. Alzheimers Dis. 7 (1): 45–61. PMID 15750214.
[10] Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM (February 2005). "Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes?". J. Alzheimers Dis. 7 (1): 63–80. PMID 15750215.
[11] "Hyperglycemia"
[12] Comninos AN, Jayasena CN, Dhillo WS (2014). "The relationship between gut and adipose hormones, and reproduction". Hum. Reprod. Update 20 (2): 153–74.doi:10.1093/humupd/dmt033. PMID 24173881.
[13] http://www.diabetes.ca/about-diabetes/what-is-diabetes
[14] Rother KI (April 2007). "Diabetes treatment—bridging the divide". The New England Journal of Medicine 356 (15): 1499–501. doi:10.1056/NEJMp078030. PMID 17429082.
[15] http://www.diabetes.org/diabetes-basics/genetics-of-diabetes.html
[16] Shoback, edited by David G. Gardner, Dolores (2011). "Chapter 17".Greenspan's basic & clinical endocrinology (9th ed.). New York: McGraw-Hill Medical.ISBN 0-07-162243-8.
[17] Williams textbook of endocrinology (12th ed.). Philadelphia: Elsevier/Saunders. pp. 1371–1435. ISBN 978-1-4377-0324-5.
[18] Malik VS, Popkin BM, Bray GA, Després JP, Hu FB (2010-03-23). "Sugar Sweetened Beverages, Obesity, Type 2 Diabetes and Cardiovascular Disease risk". Circulation 121(11): 1356–64. doi:10.1161/CIRCULATIONAHA.109.876185. PMC 2862465.PMID 20308626
[19] Malik VS, Popkin BM, Bray GA, Després JP, Willett WC, Hu FB (November 2010)."Sugar-Sweetened Beverages and Risk of Metabolic Syndrome and Type 2 Diabetes: A meta-analysis". Diabetes Care 33 (11): 2477–83. doi:10.2337/dc10-1079.PMC 2963518. PMID 20693348.
[20] Risérus U, Willett WC, Hu FB (January 2009). "Dietary fats and prevention of type 2 diabetes". Progress in Lipid Research 48 (1): 44–51.doi:10.1016/j.plipres.2008.10.002. PMC 2654180. PMID 19032965.
[21] http://www.diabetes.org/living-with-diabetes/treatment-and-care/blood-glucose-control/hyperglycemia.html
[22] http://en.wikipedia.org/wiki/Diabetes_mellitus
[23] Drug Information Portal NLM – Insulin human USANhttp://druginfo.nlm.nih.gov/drugportal/
[24] Kjeldsen T (2000). "Yeast secretory expression of insulin precursors". Applied Microbiology and Biotechnology 54 (3): 277–86. doi:10.1007/s002530000402.PMID 11030562.
[25] From SemBiosys, A New Kind Of Insulin INSIDE WALL STREET By Gene G. Marcial(AUGUST 13, 2007)
[26] "GM Safflower with Human Pro-Insulin". I-sis.org.uk

OTHER SOURCES

http://www.medicinenet.com/insulin/article.htm
http://www.doctoroz.com/article/alzheimers-diabetes-brain
http://www.endocrineweb.com/conditions/type-1-diabetes/what-insulin

IMAGE CREDITS

"Blausen 0701 PancreaticTissue" by BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff. "Blausen gallery 2014". Wikiversity Journal of Medicine. DOI:10.15347/wjm/2014.010. ISSN 20018762. - Own work. Licensed under CC BY 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Blausen_0701_PancreaticTissue.png#mediaviewer/File:Blausen_0701_PancreaticTissue.png

"InsulinHexamer" by Original uploader was Takometer at en.wikipedia - Originally from en.wikipedia; description page is/was here.. Licensed under CC BY 2.5 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:InsulinHexamer.jpg#mediaviewer/File:InsulinHexamer.jpg

"Insulin glucose metabolism ZP" by XcepticZP at en.wikipedia - Transferred from en.wikipedia to Commons by User:Shizhao using CommonsHelper.. Licensed under Public Domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Insulin_glucose_metabolism_ZP.svg#mediaviewer/File:Insulin_glucose_metabolism_ZP.svg

"Inzulín" by Original uploader was Mr Hyde at cs.wikipedia(Original text : moje foto) - Originally from cs.wikipedia; description page is/was here.(Original text : moje foto). Licensed under Public Domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Inzul%C3%ADn.jpg#mediaviewer/File:Inzul%C3%ADn.jpg

"C. H. Best and F. G. Banting ca. 1924" by Unknown - University of Toronto. Licensed under Public Domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:C._H._Best_and_F._G._Banting_ca._1924.png#mediaviewer/File:C._H._Best_and_F._G._Banting_ca._1924.png