In 2012, statistics showed that 29.1 million Americans were diabetics and a staggering 86 million Prediabetics compared to 25.8 million and 79 million respectively in 2010.
Type 2 Diabetes, a disease formerly known as adult onset diabetes, is now very common among youth with 208,000 Americans under the age of 20 diagnosed.
Insulin resistance is another hidden danger paving its way fast among the population. Statistics show that more than 40% of Americans over the age of 50 are at risk of insulin resistance with 60-70 million already diagnosed.
In insulin resistance, our cells stop responding to the insulin secreted by the Beta cells of the pancreas. Insulin is essential to make our cells open their doors to take up glucose, thus reducing its concentration in the blood.
When the cells stop responding to the insulin knocking on their doors, the pancreas keeps pumping more and more of its hormone urging the cells to open.
Eventually, the pancreas beta cells become exhausted and fail to secrete the needed amount of insulin, our blood sugar levels start to escalate resulting in diabetes.
The problem with diabetes doesn’t end there, though. Type 2 diabetes has been linked to obesity, cardiovascular diseases, hypertension, dyslipidemia, heart attacks, stroke, kidney diseases, polycystic ovarian syndrome, amputations, eye complication and blindness. It is estimated that diagnosed diabetes costs the American health care system $245 billion a year.
Understanding Glucose Control System
Our human body is a perfectly designed, highly sophisticated system of cells, nerves, organs and tissues communicating together via a series of hormones, neurotransmitters and enzymes. Each has its highly specialized job while still organizing and harmonizing with the whole symphony and functions of the entire body.
The reductionist Newtonian view that saw the body as a clock with set of gears that could be replaced or corrected individually is finally fading away. Instead of using medications as mere chemical intervention or hormonal replacements, scientists are trying to understand the underlying controlling system thus restoring our cells harmony and balance.
In case of diabetes, understanding the sophisticated blood sugar level (BSL) control mechanism with all its involved players is crucial to restore our cells ability to secrete and sense the insulin, and consequently our body ability to balance the glucose.
With the advancement of biochemical research and analysis, new players in BSL control are continuously being discovered. In the past decade, attention was focused on a class of protein breaking enzymes, the prolyl oligopeptidase (POP) family of Proteases that play a major role in balancing insulin and glucagon levels.
Insulin and glucagon are the major two hormones secreted by the pancreas and required to balance BSL. Insulin reduces glucose in the blood and glucagon raises it.
Many of these POP family enzymes have gained the interest of pharmaceutical and medical industry as they play major roles in the regulation of peptide hormones and are thus involved in many health conditions including dementia, trypanosomiasis, amnesia, depression, and type 2 diabetes.
An especially important enzyme in this class is dipeptidyl peptidase IV (DPP IV). Inhibition of this enzyme was shown to increase cell sensitivity to insulin reducing risk of obesity, metabolic syndrome and diabetes.
In 2006, Sitagliptin (Januvia) was the first anti-diabetic drug from this class of DPP-IV inhibitors to be approved by the FDA. Gliptins (DPP IV inhibitors) respond to the presence of high glucose in the blood by stimulating the release of insulin and reducing of glucagon release.
And, as this class of medication work with the enzymatic glucose control system in the body, Gliptins showed the advantage of being glucose-dependent.
This means they exert their blood sugar lowering action only when needed thereby lowering the potential risk of hypoglycemia, a major side effect of many of the other anti-diabetic medication.
Yet, efficiency is an issue. Gliptins cannot do the job alone; they are still used as a second line of treatment in conjunction with primary diabetic medications like metformin.
Advancement in Biochemical Studies & New Hopes
In July 2014, researchers at Yale school of medicine identified another enzyme that belong to the same POP family of proteases and that proved to be an important player in the regulation of BSL and pancreatic function.
This enzyme, Prolyl endopeptidase, is active in a part of the hypothalamus of the brain specifically in an area known as the ventromedial nucleus which plays an important role in the regulation of glucose metabolism.
Although the exact biochemical pathway is yet to be identified, lab tests show that prolyl endopeptidase (PREP) regulates glucose-induced insulin secretion centrally (via the central nervous system).
The discovery of this new PREP enzyme action is highly valuable piece of puzzle that lead us one step further in understanding glucose metabolism and BSL control.
According to the researchers, this enzyme makes the brain cells of the ventromedial nucleus of the hypothalamus sensitive to glucose.
As the neurons sense the increase in BSL, they order the pancreas to release the required insulin. If this enzyme is inhibited, the ventromedial nucleus ability to sense the presence of high glucose in the blood is impaired leading to reduced insulin secretion by the pancreas and increased glucagon release.
This, in turn, increases BSL and eventually leads to diabetes. Furthermore, central PREP regulation of insulin and glucagon secretion appears to be mediated by the sympathetic system, our fight-or-flight response. This fact should raise more questions about the role stress plays in the whole process.
Yet, the Journey Continues
As you can see, although both belong to the same POP family of enzymes, the action of PREP enzyme totally differ from that of the DPP IV. Still, both are highly valuable in regulating and fine tuning BSL. Simply stimulating an enzyme and/or inhibiting another won’t do the trick. Pharmaceutical medications are here to help not to heal. They are necessary and highly valuable to assist us on our healing journey until we restore our body perfectly designed balance.
Our enzymes and hormones are Orchestrating in a majestic highly organized manner… to affect healing, we need to restore body harmony and balance and, to achieve this goal, why not start today with a healthy diet and some lifestyle and stress management.
References:
Populations of the types of Diabetes
- The National Diabetes Statistics Report, June 2014. Retreived from: www.diabetes.org
- http://www.pharmacytimes.com
- Rosenblum &, Kozarich. 2003. Prolyl peptidases: a serine protease subfamily with high potential for drug discovery. Curr Opin Chem Biol.; 7(4):496-504.
- Venäläinen, Juvonen & Männistö. 2004. Evolutionary relationships of the prolyl oligopeptidase family enzymes. Eur J Biochem.; 271(13):2705-15.
- Rea & Fülöp. 2006. Structure-function properties of prolyl oligopeptidase family enzymes. Cell Biochem Biophys. 44(3):349-65.
- Conarello et. al. 2003. Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc Natl Acad Sci U S A. ;100(11):6825-30.
- Diabetes heallth pharmacist. November 2011. Retrieved from: www.diabeteshealth.com
- Kim et. al. 2014. Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice. Proceedings of the National Academies of Sciences; DOI: 10.1073/pnas.1406000111
- http://www.sciencedaily.com/releases/2014/07/140728153943.htm
This article was first published in 2011 and is currently republished for its importance.