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