VerBerkmoes 1

Clayton VerBerkmoes
David Matlack
Physiology Lab P215
12 April 2015
Paper #2: Deviation & Return to Normal Physiology of the Pancreas
In order to process nutrition within our food and create energy from
sugars, humans rely on their pancreas to function properly. The pancreas is
in charge of the secretion of pancreatic juices which contains a high
bicarbonate and digestive enzyme concentration level in order to neutralize
the acidity of the gastric juices and break down important nutrients. The
pancreas also secretes insulin and glucagon depending on certain signals
from the body. Whereas insulin (produced and secrete by beta cells) lowers
blood glucose levels, allowing cells to intake glucose and convert it into
energy, glucagon (produced and secreted by alpha cells) causes the glucose
blood levels to rise by promoting the breakdown of stored glycogen.
However certain people are affected by a lack of the insulin hormone due to
an autoimmune response in which their beta cells are destroyed. These
people are patients affected by a disease known as Type I Diabetes Mellitus.
Type I Diabetes Mellitus is an autoimmune disease in which beta cells
are mistakenly recognized by the body as foreign invaders. In response, the
immune system activates cytotoxic and T lymphocytes to target the beta
cells in the islets of Langerhans and destroy them. This is where deviation
from normal physiology begins. With the lack of beta cells, the pancreas
does not secrete insulin in response to high glucose levels (which normally

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occur upon eating). As stated above, the hormone insulin acts as a key to
GLUT-4 proteins on the membrane of cells. When insulin binds to GLUT-4, a
channel is open and glucose enters the cell. Since there is no insulin
available to unlock GLUT-4 proteins, glucose builds up in the body, causing
people to become hyperglycemic.
Hyperglycemia, the condition of above normal levels of blood glucose,
has severe consequences on the body. The high levels of glucose within the
blood leads to an increase in osmolarity. This leads to an osmotic condition
called osmotic diuresis in which intracellular fluid is extracted in order to
balance the osmotic levels of the blood. This water and glucose is filtered by
the kidney and secreted as urine in large amounts. In the end, however, the
water loss exceeds the loss of glucose and other electrolytes. This whole
process usually leads to frequent urination and severe thirst. These are both
common signs of Type I Diabetes Mellitus known as polyuria and polydipsia
respectively.
Cells which cannot receive glucose due to the lack of insulin begin to
starve. To bypass this glucose starvation, these cells begin to metabolize
fats and proteins. This leads to the severe loss of intracellular phosphorus,
potassium, and eventually amino acids. It also leads to a phenomenon
known as Diabetic Ketoacidosis. Diabetic Ketoacidosis occurs when the body
turns to fats for energy. Triglycerides are split into chains of fatty acid
molecules and glycerol. The fatty acids are catabolized by certain enzymes
into 2 carbon fragments which eventually are joined to coenzyme A,
creating acetyl coenzyme A (acetyl-CoA). Unfortunately the acetyl-CoA

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molecules are produced in such large quantities that the body cannot
oxidize them resourcefully enough in order to produce energy. Therefore
many of these acetyl-CoA molecules aggregate and form acid-ketone
bodies. Acid-ketone bodies can be used as an energy source and buffered by
the bicarbonate buffer system in the bloodstream but so many acid-ketone
bodies are formed that the body cannot handle the surplus and the pH of
the bloodstream becomes more acidic- Diabetic Ketoacidosis. If not acted on
immediately, damage will occur to cerebral function due to the high acidity
in the blood.
Although experiments and research are still being done, no cure for
Type I Diabetes Mellitus has been found. However, patients are able to
mimic a return to normal physiology via insulin therapy. Insulin Therapy is
the act of self-injecting insulin into the subcutaneous tissue and keeping
track of blood glucose levels. Two main types of therapy exist- Conservative
Insulin Therapy and Intensive Insulin therapy. Conservative Therapy is
normally undergone by younger individuals or newly diagnosed patients.
Only two injections of insulin are given daily since these patients normally
have a small amount of beta cells left in the pancreas which continue to
contribute some naturally secreted insulin but at a much slower rate than
normal. A mixture of rapid acting insulin (whose insulin begins to act in 30
minutes post-injection) and long acting insulin (whose insulin last for about
24 hours) are used. Rapid acting insulin is taken before meals and mimics
the physiology of normal postprandial insulin release whereas long acting
insulin is normally injected prior to sleep in order to assist any late
metabolic mechanism occurring while the body is at rest.

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As patients age, all beta cells cease to exist in the pancreas and
therefore a more stricter regime of insulin injections is required to mimic a
normal pancreas physiology. Intensive Therapy seeks to optimal glycemic
control via various insulin injections (more than 2) throughout the day. Rapid
acting insulin is injected for every meal and snack whereas intermediate
injections are given at night and during the early morning since the failure
to maintain normal glucose levels often results in prolongation of
hyperglycemia throughout the day. In this way the patients must act as the
intergrating center.
As all of this relies heavily on the patient, in order to mimic a return to
normal physiology, a patient must undergo many lifestyle changes. The
biggest of these is the patient acting as the integrating center of the brain
by constantly keeping track of their blood glucose level. When all of this is
done correctly, the body will begin to return to normal and act as if the
pancreas was secreting insulin and allowing for glucose to enter cells. It
should be noted that although this mimics a return to normal physiology,
the homeostasis is much more temperate to change due to control of insulin
being voluntary, not autonomic.
In conclusion, Type I Diabetes Mellitus is an autoimmune disease in
which the pancreas is no longer able to secrete insulin to the autoimmune
annihilation of the beta cells. As a result an immense amount of positive
feedback occurs in the body. An increase in blood glucose levels
(hyperglycemia) occurs due to GLUT-4 channel proteins inability to open.
The body responds by trying to dilute the bloodstream and lower the

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osmolarity of the blood and results in frequent urination (polyuria) and

excessive thirst due to water loss (polydipsia). Glucose-starved cells looks
for metabolically made energy elsewhere such as fats whose breakdown in
large quantities causes the pH of the body to become more acidic due to
Diabetic Ketoacidosis. Patients are able to survive and mimic a return to
physiology via Insulin Therapy. Conservative Therapy is the beginning point
with two insulin injections given daily while more advanced Type I patients
undergo Intensive Insulin therapy, receiving multiple subcutaneous insulin
injections a day based on food intake and daily activities. Although a return
to normal physiology is impossible, a new set point is able to be established
even though it is more temperate to change. Hopefully in the future, science
will allow for the replacement or regrowth of beta cells in the pancreas and
full pancreas physiology will return to normal.

Works Cited
Atkinson, M., & Eisenbarth, G. (2006, January 1). Type 1 diabetes: New
perspectives on disease pathogenesis and treatment. Retrieved April 9,
2015, from
http://www.sciencedirect.com/science/article/pii/S0140673601054150
Gmez Medina, D. (2011, January 1). Fisiopatologa de la diabetes mellitus
tipo 1 (DM1). Retrieved April 9, 2015, from
http://www.endocrino.org.co/files/Fisiopatologia_de_la_Diabetes_Mellitus_Tipo
_1_AM_Gomez.pdf
Inzucchi, S., & Sherwin, R. (2003, January 1). CHAPTER 236 - TYPE 1
DIABETES MELLITUS. Retrieved April 9, 2015, from
http://www.doctor33.it/cont/download-center-files/16848/cap-type-diabetesmellitus-x20299allp1.pdf

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The Pancreas & Diabetes Mellitus. (2013). In An Introduction to Human
Disease Pathology and Pathophysiology Correlations: Indiana University
M485 (1st ed., Vol. 1, pp. 159-161). Burlington, MA: World Headquarters.

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