Hormones, Receptors, and Signal
Transduction
MCB 720
March 2, 2010
John J. Kopchick, Ph.D.
Hormone -Receptor
Interactions
Hormone stems from a Greek term
meaning “to spur on.”
General
principles
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Higher organisms, from the fruit fly to
humans, are comprised of cells.
The cells often unite to form tissue
which come together to form organs
which together make up the
organism.
Cells of an organism do not live in
isolation.
The communication between cells
ultimately controls growth,
differentiation, and metabolic
processes within the organism.
Communication between cells is often by
direct cell to cell contact.
Communication frequently occurs
between cells over short and long
distances.
General principles cont...
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In cases of short and long distance
communication, a substance may be released
by one cell and recognized by a different
target cell.
In the target cell, a specific response is
induced.
Cells use an amazing number of signaling
chemicals.
These signaling molecules are termed
“hormones.”
The ability of a hormone to induce a response in
a target cell is usually mediated by a
hormone receptor on, or in, the target cell.
General characteristics
of hormones
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Hormones are molecules synthesized by specific
tissue. Classically these tissue were called
glands.
Hormones are secreted directly into the blood
which carries them to their sites of action.
Hormones are present at very low levels in the
circulatory system.
Hormones specifically affect or alter the
activities of the responsive tissue (target
tissue).
Hormones act specifically via receptors located
on, or in, target tissue.
Hormone/Receptor Interaction
Secondary Signals
Hormone
Range of
possible
pathways
Receptor
Mediator
Protein
Effectors
H1
R1
G1
E1
H2
R2
G2
E2
Possible pathways of transmission of hormonal signal. Each
hormone can work through one or more receptors; each
hormone-receptor complex can work through one or more
mediator proteins (either G proteins or other signaling
mechanism), and each mediating protein or enzyme activated
by hormone-receptor complexes can affect one or more
effectors functions.
The four primary arenas
of hormone action
Growth &
Development
Reproduction
Hormones
Maintenance of
internal
environment
Energy production,
utilization &
storage
Definitions
Endocrine - Refers to the internal secretion of biologically
active substances.
Exocrine - Refers to secretion outside the body, for
example, through sweat glands, mammary
glands, or ducts lead to the gastrointestinal.
Hormone - Substances released by an endocrine gland and
transported through the bloodstream to
another tissue where it acts to regulate
functions in the target tissue (classic
definition).
Paracrine - Hormones that act locally on cells that did
not produce them.
Autocrine - Hormones that act on cells that produced
them.
Receptors -Hormones bind to receptors molecules on cells.
A receptor must specifically recognize the
hormone from the numerous other molecules in
the blood and transmit the hormone binding
information into a cellular specific action.
Endocrine
Blood vessel
Hormone secretion
into blood by
endocrine gland
Distant target cells
Paracrine
Secretory cell
Adjacent target cell
Autocrine
Receptor
Hormone or other extra
cellular signal
Target sites on same cell
Actions of hormones &
neurotransmitters & their
interrelationships
(H,hormone; R, receptor; N,neurotransmitter.)
Examples of Hormones and
glands that produce them
Selected hormones & their functions
Hormone
Source
Principal functions
Insulin
Pancreas
Controls blood-sugar level and storage of glycogen.
Glucagon
Pancreas
Stimulates conversion of glycogen to glucose; raises
blood sugar level.
Oxytocin
Pituitary gland Stimulates contraction of the uterine muscles and
secretion of milk by the mammary glands.
Vasopressin
Pituitary gland Controls water excretion by the kidneys; stimulates
contraction of the blood vessels.
Growth hormone
Pituitary gland Stimulates growth.
Adrenocorticotrophic Pituitary gland Stimulates the adrenal cortex, which,in turn,releases
hormone (ACTH)
several steroid hormones.
Prolactin
Pituitary gland Stimulates milk production by the mammary glands
after birth of baby.
Epinephrine
Adrenal glands Stimulates rise in blood pressure, acceleration of
heartbeat, decreased secretion of insulin, and
increased blood sugar.
Selected hormones & their functions cont...
Hormone
Source
Cortisone
Adrenal glands
Thyroxine &
Triiodothyronine
Thyroid gland
Calcitonin
Thyroid gland
Parathyroid
Principal functions
Helps control carbohydrate metabolism, salt
and water balance, formation and storage of
glycogen.
Increases the metabolic rate of carbohydrates
and proteins.
Prevents the rise of calcium and phosphate in the
body.
Parathyroid gland Regulates the metabolism of calcium and
phosphate in hormone in the body.
Gastrin
Stomach
Secretin
Estrogen
Duodenum
Ovaries
Progesterone
Ovaries
Testosterone
Testes
Stimulates secretion of gastric juice.
Stimulates secretion of pancreatic juice.
Stimulates development and maintenance of
female sexual characteristics.
Stimulates female sexual characteristics and
maintains pregnancy.
Stimulates development and maintenance of male
sexual characteristics.
“Generic”
Hormone/Receptor
Interactions
Regulation of transcription by hormones that act on
the cell surface.
M odification
H
H R
2nd
M essenger
F
PP
Effector
Pre-mRNA
Response
Protein
mRNA
Types of Hormones
 Catecholamines
Hormones
and Thyroid
Small and derived from amino acids (epinephrine,
thryoxine.)
 Steroid
Hormones and Vitamin D
Relatively small and derived from cholesterol
 Prostaglandin's
Relatively small and derived from fatty acids
 Proteins
or Polypeptides
relatively large and derived from translation of hormone
specific mRNA (growth hormone, insulin)
Thyroid Hormones
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Synthesized solely in the thyroid gland ( T4; 3’,5’,3,5-Ltetra-iodothyronine).
Majority of the active form, T3 (3’,3,5-L-triiodothyronine), is produced in the peripheral tissues
through deiodination of T4.
Thyroid gland cells concentrates iodine for thyroid
hormone synthesis.
Iodine is attached to tyrosine residues on a protein,
termed thyroglobulin. Tyrosine residues are then
coupled together to yield thyronines.
Proteolytic digestion of thyroglobulin then yields T4 and
T3 in a 10:1 ratio.
Helps in the metabolism of sugars.
The half life of T4 is 7 days and that of T3 is 1 day.
Tyroxine [Tetra-iodothyronine (T4)]
I
I
NH3+
O
HO
CH2
C
H
COO Thyroid
Hormones
I
I
Tri-iodothyronine (T3)
I
I
NH3+
HO
O
CH2
I
C
H
COO -
Increase of
oxidation of sugars
by most body cells;
induction of some
enzymes
T4
T3
T3
T4
PB
T3
R
F F
T3
R
F
PP
T3
Pre-mRNA
Response
Protein
mRNA
Regulation of transcription by thyroid hormones. T3
and T4 are tri-iodotyronine and tyroxine,
respectively.
Steroid Hormones
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Produced in the adrenals, ovaries, testes, and
placenta.
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Derived from cholesterol.

Enzymes in the various glands control the final
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product. For example, cytochrome P450c11 which is
located in the adrencortical cells, is involved in
coritsol production. This enzyme is lacking in the
gonads, that do not produce cortisol or aldosterone.
Gonads, however, can produce
dihydroxytestosterone, estradiol, or
progesterone depending upon the enzymes present in
the gonadal tissue.
Over 50 different steroid metabolites have been
described.
Cholesterol Metabolism
Steroid Hormones
S
S
S
PB
R HSP
HSP
S
HSP
HSP
S
R
F
S
R
S
S
R
F
S
R
S
S
R
R HSP
HSP
S
R
PP
HSP
HSP
pre-mRNA
Response
Protein
mRNA
Regulation of transcription by steroid hormones
Catecholamines
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Are synthesized in nervous tissues from which the
adrenal medulla is derived.
Adrenal medulla is the major source for circulating
epinephrine.
Synthesized from tyrosine which is converted to
dihydroxyphenylalanine (DOPA) by tyrosine
hydroxylases.
Subsequent conversions to dopamine and then to nor
epinephrine which is released by most catecholamineproducing cells of the body.
In the adrenal medulla and a few other tissue, nor
epinephrine is converted to epinephrine.
The half life is 1-2 minutes.
Flight, fright, or fight!
Prostaglandins and Leukotrienes
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They can be produced by most cells depending upon lipid
and enzyme content of the cells.
Arachidonic acid, which is derived from lipid metabolism,
is the precursor compound.
Depending upon the lipoxygenase present in the cell,
either, HETE, prostaglandin (G2) or leukotrienes
Cyclooxygenase (involved in PGG2 synthesis) is widely
distributed throughout the body and is inhibited by
aspirin, indomethacin, and other nonsteroidal and antiinflammatory agents.
Several COX inhibitors!! - Problems
The half-life is a few seconds.
Hormone Antagonists
Examples of hormone antagonists used in therapy
Antagonist to
Use
Growth Hormone Acromegaly, Diabetes
Progesterone
Contraceptive, abortion
Glucocorticoid
Spontaneous Cushing’s
Syndrome
Mineralo-corticoid Primary and secondary
mineralocorticoid excess
Androgen
Prostate cancer
Tamoxifin
Estrogen
Breast cancer
GnRH
Prostate cancer
 -Adrenrgic
Hypertension, hyperthyroidism
Prostaglandin
Acute and chronic inflammatory
disease
Hormone Receptors
and
Signal Transduction
Hormone Receptors
Nuclear receptors
estrogens
Cytoplasmic receptors
Most steroid and thyroid hormones
Cell surface membrane
receptors
Polypeptide hormones and
catecholamines
Plasma
Membrane
Hormone
Membrane
Effects
Receptor
Cellular
Trafficking
Enzymes
Effector
Secondary Messenger
or Secondary Signal
Activated Inhibited
Nucleus
DNA Synthesis
RNA Synthesis
Protein
Synthesis
A general model for the action of peptide hormones, catecholamines, and
other membrane-active hormones. The hormone in the extra cellular fluid
binds to the receptor and activates associated effector(s) systems, that
may or may not be in the same molecule. This activation results in
generation of an intracellular signal or second messenger that, through a
variety of common and branched pathways, produces the final effects of
the hormone on metabolic enzyme activity, protein synthesis, or cellular
growth and differentiation.
Receptors that span the
membrane Seven times
cAMP
cAMP: synthesis and degradation
cAMP
Amino acid Phosphorylation is very
important in intracellular signal
transduction
ATP
ATP
S Serine
Protein Kinases – transfer terminal Phosphate groups
from ATP to Serine, Threonine, or Tyrosine residues
in proteins
Result in activation or inactivation of the recipient protein !
S Serine
Amino acids
that can be
phosphorylated
Threonine
Y Tyrosine
Peptide hormone receptors
Huising, et.al.
J. Endo. 2006. 189:1-25
General View
of
Metabolism
Levels of blood sugar
(glucose) regulate secretion
of hormones from
the pancreas
Pancreas secretes
insulin when glucose
levels are high
Insulin binds to
insulin receptors on
fat and muscle and
“promotes” glucose
uptake
Overall effect: blood glucose
levels return to normal
Glucose Tolerance Test
The Insulin Receptor
Responsible for clearance of glucose
 In addition to binding insulin, it
possesses a tyrosine kinase activity
 It is involved in many cellular
activities

Glucose Transporter Intracellular Trafficking
Insulin Receptor
Tyrosine
kinase
Insulin-mediated
Insulin-mediatedglucose
glucosetransport
transportsignaling
signalingpathway
pathway
Insulin
IR
a
a


Cell membrane
P
IRS
PI3K
Glut4
Akt
P
Xiao Chen, 2006
Insulin-mediated glucose transport signaling pathway
Insulin-mediated glucose transport signaling pathway
IR
glucose
a
Insulin
a


Cell membrane
P
IRS
PI3K
Akt
P
Xiao Chen, 2006
Expectancy; Low = 73.6; High =
Time, Nov, 2006
Obesity is a Global Pandemic Disease
USA Today
Feb. 9, 2010
USA Today
Feb. 9, 2010
Reduce
USA Today
Feb. 9, 2010
41 grams
Expectancy; Low = 73.6; High =
Time, Nov, 2006
Insulin Signaling Pathways by C. Hooper
http://www.abcam.com/index.html?pageconfig=resource&rid=10602&pid=7
Cartoon of Intracellular Signaling System Used By
Many Peptide Hormones and Growth Factors
l
For example
– Insulin
– EGF
Tyrosine kinase receptors are a family of receptors with a similar
structure. They each have a tyrosine kinase domain (which
phosphorylates proteins on tyrosine residues), a hormone binding
domain, and a carboxyl terminal segment with multiple tyrosines for
autophosphorylation. When hormone binds to the extra cellular domain
the receptors aggregate.
When the receptors aggregate, the tyrosine kinase domains
phosphorylate the C terminal tyrosine residues.
This
with
with
This
phosphorylation produces binding sites for proteins
SH2 domains. GRB2 is one of these proteins. GRB2,
SOS bound to it, then binds to the receptor complex.
causes the activation of SOS.
SOS is a guanyl nucleotide-release protein (GNRP). When this
is activated, it causes certain G proteins to release GDP and
exchange it for GTP. Ras is one of these proteins. When ras
has GTP bound to it, it becomes active.
Activated ras then causes the activation of a cellular kinase
called raf-1.
Raf-1 kinase then phosphorylates another cellular kinase called
MEK. This cause the activation of MEK.
Activated MEK then phosphorylates another protein kinase called MAPK
causing its activation. This series of phosphylating activations is called
a kinase cascade. It results in amplification of the signal.
Adapted from: Dr. Donald F. Slish,
Biological Sciences Department,
Plattsburgh State University, Plattsburgh,
NY.
Among the final targets of the kinase cascade are transcriptions factors (fos
and jun showed here). Phosphorylation of these proteins causes them to
become active and bind to the DNA, causing changes in gene transcription.
Examples of therapeutics
developed based on these types
of receptors and the associated
tyrosine kinase signaling system
Erbitux – Imclone
Iressa - AstraZeneca
Gleevec – Novartis
Herceptin - Genentech
EGF Receptor Signal Transduction Pathway
SIGMA-ALDRICH
Tyrosine kinase
Cell Proliferation
Epidermal Growth Factor Receptor
EGF
Cysteine
Rich
Domain
Receptor
EGF
Dimerization
Cell
Membrane
Tyrosine
Kinase
Domain
*
*
*
P P
*
*
*
Signal
Transduction
EGFR Family





The epidermal
growth factor
(EGF) family of
receptor tyrosine
kinases consists of
four receptors,
ErbB1 (EGFR)
ErbB2 (Her/Neu)
ErbB3 (HER3)
ErbB4 (HER4).
Non-small cell lung cancer


Non-small cell lung cancer comprises over
75% of all lung cancers. In 2006, more
than 338,000 cases of the disease are
expected to be diagnosed in the seven
major pharmaceutical markets. High unmet
needs of therapy still persist for this
tumor type. The overall survival of NSCLC
patients remains below 12 months.
The EGfR is expressed on these
cells.
Epidermal Growth Factor Receptor in Non–Small-Cell Lung Carcinomas:
Correlation Between Gene Copy Number and Protein Expression and Impact on
Prognosis
Fred R. Hirsch, Marileila Varella-Garcia, Paul A. Bunn, Jr, Michael V. Di Maria, Robert Veve, Roy M.
Bremnes, Anna E. Barón, Chan Zeng, Wilbur A. Franklin
Journal of Clinical Oncology, Vol 21, 2003: 3798-3807, 2003
• The percentage of EGFR
positive tumor cells per slide
(0% to 100%) was multiplied
by the dominant intensity
pattern of staining (1,
negative or trace; 2, weak; 3,
moderate; 4, intense);
therefore, the overall score
ranged from 0 to 400 (Fig 1).
Specimens with scores 0 to
200, 201 to 300, and 301 to
400 were respectively
classified as having negative
or low, intermediate, and
high levels of expression.
Influence of histological type, smoking history and chemotherapy on survival
after first-line therapy in patients with advanced non-small cell lung cancer
Itaya , Yamaoto, Ando, Ebisawa, Nakamura, Murakami, Asai, Endo and Takahashi
Cancer Science
Volume 98, Page 226, 2007
• For overall survival,
smoking history and
histology were
significant
prognostic factors.
The 2-year overall
survival rates were
as follows: smokers,
17%; non-smokers,
52%, P < 0.0001;
Iressa (gefitinib tablets)
AstraZeneca.
IRESSA is indicated as
monotherapy for the
continued treatment of
patients with locally
advanced or metastatic
non-small cell lung
cancer after failure of
both platinum-based and
docetaxel
chemotherapies who are
benefiting or have
benefited from
IRESSA.
Iressa (gefitinib tablets)
AstraZeneca.
• Mechanism of Action
•
The mechanism of the clinical
antitumor action of gefitinib is
not fully characterized.
•
Gefitinib inhibits the
intracellular phosphorylation of
numerous tyrosine kinases
associated with transmembrane
cell surface receptors, including
the tyrosine kinases associated
with the epidermal growth
factor receptor (EGFR-TK).
•
EGFR is expressed on the cell
surface of many normal cells and
cancer cells. No clinical studies
have been performed that
demonstrate a correlation
between EGFR receptor
expression and response to
gefitinib.
Gefitinib is an anilinoquinazoline
with the chemical name 4Quinazolinamine, N-(3-chloro4- fluorophenyl) -7-methoxy6- [3-4-morpholin) propoxy]
C22H24ClFN4O3
Zactima
Tyrosine Kinase Inhibitor for Treatment of
Lung Cancer
•
•
•
•
Zactima (ZD6474) is an orally available Tyrosine Kinase Inhibitor (TKI)
under development by AstraZeneca for the treatment of solid tumours.
Following promising results in early clinical trials, Zactima has now
progressed to phase III development in Non-Small Cell Lung Cancer
(NSCLC), its primary indication.
If phase III trials prove successful, analysts believe Zactima could be
on the market by 2008 and help to fill the void left by recent setbacks
with Iressa (gefitinib), its first TKI for lung cancer.
At the beginning of the year, AstraZeneca withdrew its marketing
application for Iressa in Europe. This followed the release of new longterm data that showed it to be no better than placebo in prolonging
patients' lives.
Meanwhile, in the US Iressa will soon be available only to existing
NSCLC patients who have already shown treatment benefit and will not
be prescribed to new patients. While Iressa has stalled in Europe and
the US, it is approved in more than 30 countries elsewhere.
http://www.drugdevelopment-technology.com/projects/zactima/ AstraZeneca
BCR - ABL
•
•
•
The exact chromosomal defect in Philadelphia chromosome is
translocation. Parts of two chromosomes, 9 and 22, swap places. The result
is that part of the BCR ("breakpoint cluster region") gene from chromosome
22 (region q11) is fused with part of the ABL gene on chromosome 9 (region
q34). Abl stands for "Abelson", the name of a leukemia virus which carries a
similar protein.
The result of the translocation is a protein of p210 or sometimes p185
weight (p is a weight fraction of cellular proteins in kDa). The fused "bcr-abl"
gene is located on the resulting, shorter chromosome 22. Because abl
carries a domain that can add phosphate groups to tyrosine residues
(tyrosine kinase) the bcr-abl fusion gene is also a tyrosine kinase. (Although
the bcr region is also a serine/threonine kinase, the tyrosine kinase function
is very relevant for therapy, as will be shown.)
The fused bcr-abl protein interacts with the interleukin 3beta(c) receptor
subunit. The bcr-abl transcript is constitutively active, i.e. it does not require
activation by other cellular messaging proteins. In turn, bcr-abl activates a
number of cell cycle-controlling proteins and enzymes, speeding up cell
division. Moreover, it inhibits DNA repair, causing genomic instability and
potentially causing the feared blast crisis in CML.
BCR-ABL
•
•
•
The exact chromosomal defect in Philadelphia chromosome is translocation. Parts of two
chromosomes, 9 and 22, swap places. The result is that part of the BCR ("breakpoint cluster
region") gene from chromosome 22 (region q11) is fused with part of the ABL gene on
chromosome 9 (region q34). Abl stands for "Abelson", the name of a leukemia virus which carries
a similar protein.
The result of the translocation is a protein of p210 or sometimes p185 weight (p is a weight
fraction of cellular proteins in kDa). The fused "bcr-abl" gene is located on the resulting, shorter
chromosome 22. Because abl carries a domain that can add phosphate groups to tyrosine
residues (tyrosine kinase) the bcr-abl fusion gene is also a tyrosine kinase. (Although the bcr
region is also a serine/threonine kinase, the tyrosine kinase function is very relevant for therapy,
as will be shown.)
The fused bcr-abl protein interacts with the interleukin 3beta(c) receptor subunit. The bcr-abl
transcript is constitutively active, i.e. it does not require activation by other cellular messaging
proteins. In turn, bcr-abl activates a number of cell cycle-controlling proteins and enzymes,
speeding up cell division. Moreover, it inhibits DNA repair, causing genomic instability and
potentially causing the feared blast crisis in CML. (Chronic myelogenous leukemia)
Gleevec
(imatinib mesylate, aka STI-571)
FDA APPROVES GLEEVEC FOR LEUKEMIA TREATMENT
The Food and Drug Administration today announced the approval of
Gleevec (imatinib mesylate, also known as STI-571), a promising new
oral treatment for patients with chronic myeloid leukemia (CML) -- a
rare life-threatening form of cancer. FDA reviewed the marketing
application for Gleevec in less than three months under its
"accelerated approval" regulations.
Novartis, May 10, 2001
Used in the treatment of Chronic Myeloid Leukemia (CML) and
Gastrointestinal Stromal Tumors (GIST)
Mechanism of Action
Imatinib mesylate is a protein-tyrosine
kinase inhibitor that inhibits the Bcr-Abl
tyrosine kinase, the constitutive
abnormal tyrosine kinase created by the
Philadelphia chromosome abnormality in
chronic myeloid leukemia (CML). It
inhibits proliferation and induces
apoptosis in Bcr-Abl positive cell lines as
well as fresh leukemic cells from
Philadelphia chromosome positive chronic
myeloid leukemia. In colony formation
assays using ex vivo peripheral blood and
bone marrow samples, imatinib shows
inhibition of Bcr-Abl positive colonies
from CML patients. In vivo, it inhibits
tumor growth of Bcr-Abl transfected
murine myeloid cells as well as Bcr-Abl
positive leukemia lines derived from CML
patients in blast crisis.
Gleevec
(Novarits)
In vitro studies
demonstrate imatinib is
not entirely selective; it
also inhibits the receptor
tyrosine kinases for
platelet-derived growth
factor (PDGF) and stem
cell factor (SCF), c-Kit,
and inhibits PDGF
mediated cellular events
Monoclonal Antibody Therapy
Antibody to EGF R binds and blocks EGF from binding
EGF
Erbitux, Imclone
Cell
Membrane
Tyrosine
Kinase
Domain
Therefore, no tyrosine kinase
activity and
no intracellular signaling
Herceptin
is the first humanized antibody approved for the
treatment of HER2-positive metastatic breast cancer.
Herceptin is designed to target and block the function
of HER2 protein over expression.
Genentech
HER 2 = Human Epidermal Growth Factor
Receptor 2
Herceptin,
a monoclonal antibody,
binds to HER2
and ultimately results
in destruction of the cell
So two targets to inhibit EGF/EGFR signaling
1
EGF
Receptor
EGF
Dimerization
Cell
Membrane
Tyrosine
Kinase
Domain
P P
Signal
Transduction
2
Colored slide: D-88
Diabetes
Diabetes - from the Greek word, diabetes, meaning “a
crossing over or passing through”. Any of several metabolic
disorders marked by excessive discharge of urine and
persistent thirst. (The American Heritage Dictionary).
Diabetes mellitus - a chronic disease of pancreatic origin,
characterized by insulin deficiency, subsequent inability to utilize
carbohydrates, excess sugar in the blood and urine, excessive thirst,
hunger, and urination, weakness, emaciation, imperfect combustion of
fats resulting in acidosis, and, without injection of insulin, results in
coma and death. (The American Heritage Dictionary).
Diabetes, con’t.


Type I or Insulin Dependent Diabetes
Mellitus (IDDM) – Also called juvenile
diabetes - lack of insulin
Type II or Non Insulin Dependent
Diabetes Mellitus (NIDDM) – Also called
adult onset diabetes - insulin present but
cells do not respond that is they
are“insulin resistant”.
Facts: (Diabetes 1996 Vital Statistics, ADA)
16-20 million Americans have diabetes.
385,000 diabetes die each year.
625,000 new cases each year.
Every minute of every day, someone new is diagnosed with
diabetes.
127,000 children (younger that age 20) have diabetes.
11% of the U.S. population, age 65-74, has diabetes.
Diabetes, con’t.
Diabetic eye disease (retinopathy): by 15 years after
diagnosis of diabetes, retinopathy is present in
97% of insulin users and 80% of non-insulin users.
About 20% of people with diabetes have kidney
disease (nephropathy).
40% of the deaths associated with diabetes are due to
heart disease.
Types of diabetes mellitus
(Diabetes 1996 Vital Statistics, ADA)
Type I or insulin-dependent diabetes mellitus (IDDM) - Low
or absent levels of endogenous insulin. Dependent on insulin therapy to
prevent ketoacidosis and sustain life. Onset predominantly before age 30
but can occur at any age. Onset is usually abrupt and patients are usually
thin. Cause appears to be a combination of genetic and environmental
determinants. Pancreatic islet cells are destroyed.
Type II or non-insulin dependent diabetes mellitus
(NIDDM) - Normal to High insulin levels characterize most patients,
indicating insulin resistance in tissues. Often see development of low
insulin levels as the disease progresses. Patients are not prone to
ketoacidosis during normal circumstances. Although not dependent on
insulin therapy for survival, many require it for adequate blood glucose
control. Onset is predominantly after age 40, particularly in whites,
and often asymptomatic; most patients are obese. Cause appears to be a
combination of genetic and environmental lifestyle determinants. Drugs
are available to promote insulin release from the pancreas or to allow
cells to be more sensitive to insulin action.
Types of diabetes, con’t.
Gestational Diabetes Mellitus (GDM) - Glucose intolerance that has its
onset or recognition during pregnancy. Associated with older age, obesity,
and family history of diabetes. Risk for subsequent NIDDM is increased.
Newborn offspring often have macrosomia and may also be at increased
risk for developing NIDDM.
Diabetes insipidus - Caused by the total or partial lack of the hormone
vasopressin, also called antidiuretic hormone. Blood glucose is normal, but
increased urine output with accompanying thirst.
Other types of diabetes - Diabetes secondary to other conditions with
hyperglycemia at a level diagnostic of diabetes.
Impaired Glucose Tolerance (IGT) - Blood glucose levels that are higher
than normal but not diagnostic for diabetes mellitus. Risk for subsequent
NIDDM is increased.