1. Fibrosis in the Urinary Bladder caused by Diabetes Mellitus Type II
Student: Nadia Tsado
Mentors: Matthew H. Ho, M.D., Ph.D., Gaby Nolazco, M. Sc.
Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles Drew University of
Medicine and Science, Los Angeles, California.
Fibrosis in the Urinary Bladder caused by Diabetes Mellitus Type II
Student: Nadia Tsado
Mentors: Matthew H. Ho, M.D., Ph.D., Gaby Nolazco, M. Sc.
Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles Drew University of
Medicine and Science, Los Angeles, California.
HYPOTHESISHYPOTHESIS
MATERIALS AND METHODSMATERIALS AND METHODS
RESULTSRESULTS
CONCLUSIONCONCLUSION
I would like to thank Dr. Matthew Ho and Gaby Nolazco of
the Charles Drew research endocrinology Department. Dr.
Donzalez- Cadavid has also contributed to make this project
possible with the feedback he has given to this project. I thank
the NIH/Step Up Program, Dee Flemming and Emma Taylor
for giving me an opportunity to do research in the lab for two
consecutive summers.
The hypothesis of this study is that diabetes Mellitus Type II causes
urinary bladder disorders as a result of an over production of fibrosis
and a decrease in smooth muscle cells in the detrusor.
BACKGROUNDBACKGROUND
Diabetes affects the bladder causing smooth muscle tissue reduction as well as
an increase of collagen accumulation and fibrosis, thus the bladder is not able to
function properly. Type II diabetes, in both humans and rat, is also associated with
loss of smooth muscle (SM) tissue within the bladder together with an increase in
fibrosis, arterial stiffness and increased oxidative stress. The concept that a
progressive fibrosis of the SM tissue within the bladder is responsible for bladder
disorder associated with diabetes, aging, heavy smoking, with that said pelvic
surgery has become more of interest. The detrusor is the wall of the bladder that is
made up of smooth musclet is responsible for removing urine from the bladder.
There have been numerous studies on other organs that have been affected by type
II diabetes, which can lead to an increase in collagen and an decrease in smooth
muscle. The detrusor (smooth muscle of the bladder) is unable to function because
of the increase of collagen which leads to an increase of fibrosis in the urinary
bladder.
The animals consisted of four groups (eight animals per group); non-diabetic, (lean Zucker fa/fa
rat, LZFR), diabetic treated with Molsidomine, an NO donor, Allopurinol, a drug used to treat
high uric acid in the blood that causes insulin resistance, and type II diabetic mellitus (Zucker
diabetic fa/fa rat, ZDFR). Animal bladders were extracted and subjected to paraffin-wax
embedding. Paraffin embedded tissue sections endured immunohistochemistry techniques such
as: Masson trichrome, a procedure that stains the collagen/smooth muscle, Hematoxylin Eosin
which stains the cell membrane, and Picro Sirius red which stains collagen type1 and collagen
III. The total reduction of the smooth muscle cells (SMC)/collagen ratio was confirmed by
quantitative image analysis (QIA). The ratio of type I collagen to type III collagen was also
confirmed by QIA.
There was a significant increase of collagen in the urinary
bladder of type II DM more so than the non-DM group.
As a result of the increase in collagen in the diabetic and
diabetic treated group there is a decrease in smooth
muscle The collagen III/I decreased in the diabetic and
treated bladders.
As a result the data shows that type II DM can cause an
increase in both fibrosis and smooth muscle cells turnover in
the urinary bladder, which may subsequently cause urinary
bladder disorders. Fibrosis occurs over time in a bladder
affected by type II DM. This overproduction of fibrosis can
cause neuropathy and stress urinary incontinence (SUI. ) in
the bladder as the type II DM continues to affect the bladder
Picro Sirius Red
20x
LZDFR ZDFR
Masson Trichome
20x
Results
ZDF
mol
ZDF
allo
Hematoxylin
&Eosin
10x
REFERENCESREFERENCES
1. Kovanecz I, Nolazco G, Ferrini MG, et al. Early onset of
fibrosis within the arterial media in a rat model of type 2
diabetes mellitus within erectile dysfunction. BJU
International. 2008;103:1396-1404
2. Kebapc N, Yenimez A, Efe B, Entok E,Demirustu C.
Bladder dysfunction in type 2 diabetic patients. 2007;26:814-
819
ACKNOWLEDGEMENTSACKNOWLEDGEMENTS
AIMAIM
The aim of this study is to determine whether diabetes mellitus
type II affects the smooth muscle to collagen ratio, which together
with TGF- beta is the marker of fibrosis, in the urinary bladder.
Another aim is to verify whether diabetes mellitus type II affects the
type I and III collagen ratio.