1. Introducing the Endocrine System

2. IB Assessment Statement
State that the endocrine system consists of glands that release hormones that are transported in the blood.
Crash Course Video on the Endocrine System

3. Animals have two systems of internal communication and regulation:
The endocrine system and the nervous system act individually and together in regulating an animal’s physiology
Animals have two systems of internal communication and regulation:
the nervous system
and the endocrine system

4. The nervous system conveys high-speed electrical signals along specialized cells called neurons
The endocrine system secretes hormones that coordinate slower but longer-acting responses

5. Overlap Between Endocrine and Nervous Regulation
The endocrine and nervous systems function together in maintaining homeostasis, development, and reproduction

6. What is Homeostasis?
Refers to a state of constancy in a system.
In its normal, or resting, state, a system often is said to be in homeostasis.
When events occur that disrupt the normal state, the system is able to respond and restore homeostasis.
Physiologists use the term homeostasis to refer to maintenance of a constant internal environment despite fluctuations in external conditions.

7. Examples of physiological conditions requiring homeostasis:
Temperature
Concentration of Waste Products (urea, CO2)
O2 concentration
pH of blood
Energy Requirements/Blood glucose concentration
Water/Ion balance (Na+, K+, Cl-)
Volume/Pressure of blood
Metabolic rate (rate of cellular respiration)

8. Homeostasis – is important for our internal environment
Internal environment consists of:
Blood
Tissue fluid

10. IB Learning Objective
Define Homeostasis and explain how it is regulative by a negative feedback system.

12. Negative Feedback – the mechanism of homeostasis
Type of control in which conditions being regulated are brought back to a set value (example body temperature)
Negative feedback requires a detector device that measures the value
When the value falls below or above the set value an effector device is activated (example sweating when body temperature rises)

13. Homeostatic Mechanism
Negative-Feedback Regulation
An external stimuli or activity alters a condition of the internal environment, which triggers a response by the body. This response reverses the altered condition.
Homeostatic Mechanism
The mechanism known as negative-feedback regulation maintains homeostasis. The “receptor, control center, effector” structure of a homeostatic system (described in the previous slide) enables negative-feedback regulation to occur. When a large external change is detected by the receptor, a signal is sent to, and is interpreted by the control center, resulting in a response by the effector to minimize the internal impact of the large external change. This is negative-feedback regulation. The original external change is counteracted internally so that the internal change is small or nonexistent.
Positive-feedback regulation also is seen in biological systems, but it is not utilized for maintaining homeostasis. Rather, positive-feedback is used to augment a change within an organism. For example, during birth, the uterus contracts to expel the infant. Positive-feedback causes these contractions to continue until the birth is complete. So, whereas negative-feedback helps homeostatic systems to remain fairly constant by responding to changes in the external environment, positive-feedback promotes the change.
References:
Langley, L.L. (Ed.). (1973). Homeostasis: Origins of the Concept. Langley, National Library of Medicine. Stroudsburg, PA:Dowden Hutchinson, and Ross Inc.
Sherwood, Lauralee. (1997). Human Physiology: From Cells to Systems (3rd ed.). West Publishing Co. 13

14. Effectors – in Negative Feedback
Effectors are of 2 types: Muscles & Glands

15. NEGATIVE FEEDBACK MECHANISM
Rise above
normal value
Corrective Mechanism
negative feedback
normal value
normal value
negative feedback
Fall below
normal value
Corrective Mechanism

16. Endocrine system
Animal hormones are chemical signals that are secreted by endocrine glands into the circulatory system and communicate regulatory messages within the body
Hormones reach all parts of the body, but only target cells are equipped to respond
State that the endocrine system consists of glands that release hormones that are transported in the blood.

18. Simple endocrine pathway
LE 45-2a
Pathway
Example
Low blood
glucose
Stimulus
Receptor
protein
Pancreas
secretes
glucagon ( )
Endocrine
cell
Blood
vessel
Target
effectors
Liver
Response
Glycogen
breakdown,
glucose release
into blood
Simple endocrine pathway

19. LE 45-2b Pathway Example Stimulus Suckling Sensory neuron
Hypothalamus/
posterior pituitary
Neurosecretory
cell
Posterior pituitary
secretes oxytocin
( )
Blood
vessel
Target
effectors
Smooth muscle
in breast
Response
Milk release
Simple neurohormone pathway

20. LE 45-2c Pathway Example Simple neuroendocrine pathway Stimulus
Hypothalamic
neurohormone
released in
response to
neural and
hormonal
signals
Sensory
neuron
Hypothalamus
Neurosecretory
cell
Hypothalamus
secretes prolactin-
releasing
hormone ( )
Blood
vessel
Anterior
pituitary
secretes
prolactin ( )
Endocrine
cell
Blood
vessel
Target
effectors
Mammary glands
Response
Milk production
Simple neuroendocrine pathway

21. LE 45-3 SECRETORY CELL SECRETORY CELL Hormone molecule Hormone
VIA
BLOOD
VIA
BLOOD
Signal receptor
TARGET
CELL
TARGET
CELL
Signal
transduction
pathway
Signal
receptor OR
Cytoplasmic
response
DNA
Signal
transduction
and response
mRNA
DNA
Nuclear
response
NUCLEUS
Synthesis of
specific proteins
NUCLEUS
Receptor in plasma membrane
Receptor in cell nucleus

22. IB Assessment Statement
Explain the control of body temperature, including the transfer of heat in blood, and the roles of the hypothalamus, sweat glands, skin arterioles and shivering.

23. IMPORTANCE OF CONSTANT TEMPERATURE
enzymes are proteins that are important to all biochemical activities in a living organisms
Enzymes work best at optimum temperature, and are denatured by deviation from this.

24. Cell membranes become fragile as temperatures rise
IMPORTANCE OF CONSTANT TEMPERATURE
Cell membranes become fragile as temperatures rise
Diffusion rates across cell membranes increase by higher temperatures and decrease in lower temperatures.
Liquid such as blood becomes more viscous (thick) as the temperature falls

25. Mechanism to Maintain Body temperature
Maintaining constant temperature,
Generation of Heat:
Biochemical reactions, such as respiration generate heat.
Movement generates heat by friction within muscles

26. Mechanism to Maintain Body temperature
Maintaining constant temperature,
Losing heat:
Evaporation of water, from the lungs and sweat from the skin.
Excretion: Urine and Faeces heat is lost as theses substances are removed from the body.

27. Mechanism to Maintain Body temperature
Insulation:
Fat stores under the skin prevent heat loss.

28. Mechanism to Maintain Body temperature
The hypothalamus as the co-ordinator of temperature regulation:
Vasoconstriction: is a cold adaptation narrowing of arterioles that reduces blood flow to the surface of the skin is coupled with a dilation of the horizontal shunt vessels. This prevents heat loss from blood near the skin surface and retains heat in the body core for essential organs.
Vasodilation: is an adaptation to warm conditions in which arterioles dilate sending more blood closer to the skin surface from where heat can be radiated to the surrounding environment. The horizontal shunt vessels are constricted sending most blood closer to the skin surface. Additionally sweat (mainly water) is released onto the surface of the skin where it enters the vapour phase when warmed by the heat carried by blood. Therefore the vapour of sweat carried away heat energy from blood.

29. Thermoregulation is the regulation of body temperature
Skin – hot and cold receptors

30. Thermoregulation is the regulation of body temperature
Hypothalamus in brain
Control Unit
Monitors the temperature of the blood and compares it to a set value close to 37  C
heat gain centre in the posterior part
heat loss centre in the anterior part

31. Thermoregulation – Response to overheating
Skin
Heat exchange between body and surrounding occur through our skin
Sweat glands produce sweat. Water evaporates off the skin and this has a cooling effect.
Capillaries will dilate (vasodilation). More blood will flow through the skin. The blood transfers heat from the core to the skin. This heat will be lost to environment
Hair erector muscles which relax. Allows more air flow on skin, which promotes cooling.

32. BODY TEMPERATURE DROPS BELOW NORMAL
If core body temperature drops, the hypothalamus:
Skin capillaries (vasoconstrict) become narrow and they bring less blood to the skin.
Hair erector muscles raise hairs and traps a layer of still air, thus reducing convection.
causes the skeletal muscles to contract involuntarily—to “shiver.”
This causes the body temperature to increase.

33. Maintaining Homeostasis
An Example of Feedback Inhibition
Thermostat senses temperature change and switches off heating system
Room temperature increases
Room temperature decreases
Homeostasis is the process by which organisms keep internal conditions relatively constant despite changes in external environments. A home heating system uses a feedback mechanism to maintain a stable, comfortable environment within a house.
Thermostat senses temperature change and switches on heating system

34. Thermoregulation
Cold: when cold the following events occur to reduce heat loss and raise temperature.
Lower than regulation temperature blood reaches the hypothalamus.
The hypothalamus signals the vasoconstriction (narrowing) of arterioles
Muscle effectors are produces the rapid contraction relaxation of muscles known as shivering which produces more body heat.
Hot:
Sweat is secreted onto the surface of skin when body temperature is high
Sweat is largely composed of water which has a high specific heat capacity (absorbs a heat easily)
Body heat is transferred from skin and blood to the sweat
The sweat evaporates transferring heat away and in doing so cools the body

38. Videos/ Tutorials on Thermoregulation of Body Temperature

39. IB Assessment Statement
Explain the control of blood glucose concentration, including the roles of glucagon, insulin and α and β cells in the pancreatic islets.

40. Why blood sugar is regulated
Blood sugar concentration is regulated for a number of reason amongst which:
Osmosis. content of a tissue is determined by the concentration of the surrounding tissues.
Respiration: Some tissues are entirely dependent on blood sugar as a respiratory substrate being unable to either store glucose of metabolise fat.

41. Insulin and Glucagon: Control of Blood Glucose
The pancreas secretes insulin and glucagon, antagonistic hormones that help maintain glucose homeostasis
Glucagon is produced by alpha cells
Insulin is produced by beta cells

43. LE 45-12 Body cells take up more glucose. Insulin Beta cells of
pancreas
release insulin
into the blood.
Liver takes
up glucose
and stores it
as glycogen.
STIMULUS:
Rising blood glucose
level (for instance, after
eating a carbohydrate-
rich meal)
Blood glucose level
declines to set point;
stimulus for insulin
release diminishes.
Homeostasis:
Blood glucose level
(about 90 mg/100 mL)
Blood glucose level
rises to set point;
stimulus for glucagon
release diminishes.
STIMULUS:
Dropping blood glucose
level (for instance, after
skipping a meal)
Alpha cells of pancreas
release glucagon into
the blood.
Liver breaks
down glycogen
and releases
glucose into the
blood.
Glucagon

44. Target Tissues for Insulin and Glucagon
Insulin reduces blood glucose levels by
Promoting the cellular uptake of glucose
Slowing glycogen breakdown in the liver
Promoting fat storage

45. Glucagon increases blood glucose levels by
Stimulating conversion of glycogen to glucose in the liver
Stimulating breakdown of fat and protein into glucose

47.   Explain the control of blood glucose concentration, including the roles of glucagon, insulin and α and β cells in
the pancreatic islets.(3
a) Low glucose concentration is detected by the pancreas.
b) Alpha cells in the pancreatic islets secret glucagon.
c)Glucagon flows through the blood to receptors on liver cells.
d)Liver responds by adding glucose to blood stream.
h) High blood glucose levels stimulate the beta pancreatic cells
a) Beta pancreatic cells secrete insulin.
f)Insulin flows through the blood to the receptors on liver cells.
g)Insulin stimulates the liver to remove blood glucose and store this as glycogen (insoluble)

48. Glucose Homeostasis Chart
Liver breaks down glycogen to create glucose
Raises blood-glucose
Glucose uptake by muscle/fat tissue
Lowers blood-glucose
Result
Glucagon
Insulin
Effector
Alpha-cell of the pancreas
Beta-cell of the pancreas
Control Center
Glucose transporter
Receptor
Low Blood Sugar
Do not meet energy requirements of cell
High Blood Sugar
Toxic
Condition
Glucose Homeostasis Chart
Glucose is used by many organisms as fuel, but it is vital that glucose levels be tightly regulated. Too little glucose will lead to starvation, while too much is toxic. Glucose homeostasis is accomplished through highly complex mechanisms involving many different molecules, cell types, and organs.
Briefly, when glucose enters the bloodstream (after the digestion of food), it is detected by specialized cells in the pancreas, called -cells. These cells respond to the rising blood-glucose concentration by releasing the enzyme, insulin. Insulin then signals to other tissues in the body (i.e., muscle cells and adipose tissue) to take in glucose to be used as energy (in muscle cells) or stored for later use (in adipose tissue). The result is a lowering of blood-glucose concentration to non-toxic levels.
In times of low glucose intake (between meals or in cases of starvation) the -cells of the pancreas release the enzyme, glucagon. This enzyme directs the liver to break down stored glycogen into glucose and release this glucose into the bloodstream, thereby raising blood-glucose concentration to a desired level. The glucose transporters expressed on the - and -cells that bind glucose are the receptors of this homeostatic system. The - and -cells, themselves, are the control centers. They process information from the receptors and respond to it in a way that will maintain a constant internal environment. Insulin and glucagon are the effectors. This system is complex; the - and -cells working continuously to achieve the optimal, homeostatic blood-glucose concentration.
References:
Langley, L.L. (Ed.). (1973). Homeostasis: Origins of the Concept. Langley, National Library of Medicine. Stroudsburg, PA:Dowden Hutchinson, and Ross Inc.
Sherwood, Lauralee. (1997). Human Physiology: From Cells to Systems (3rd ed.). West Publishing Co. 48

49. normal blood glucose level normal blood glucose level
Pancreas secretes insulin
Liver coverts glucose to glycogen
Soon after a meal
Too High
Blood glucose level falls
normal blood glucose level
normal blood glucose level
Pancreas secretes less insulin
Liver converts glycogen to glucose
Long after a meal
Too Low
Blood glucose level rises

52. IB Assessment Statement
Distinguish between type I and type II diabetes.

53. Diabetes Mellitus Type I
Diabetes mellitus (type I) is perhaps the best-known endocrine disorder
The onset is usually during childhood
It is caused by a deficiency of insulin
beta cells fail to produce insulin
Requires insulin injections to control glucose levels

54. Type II Diabetes
The onset is after childhood
Target cells become insensitive to insulin
Insulin injections are usually NOT needed
Low carbohydrate diet usually controls the condition

56. Glucose Homeostasis Lower Blood Glucose Higher Blood Glucose
Between meals
Alpha-cells release glucagon stimulate glycogen breakdown and gluconeogenesis
beta-cells release insulin stimulate glucose uptake by peripheral tissues
Glucose Homeostasis
Here is a diagram of glucose homeostasis. When we eat food, our blood glucose concentration rises, which stimulates insulin secretion from -cells and eventual glucose absorption by peripheral tissues. In between meals or in times of starvation, we are not taking in glucose and, therefore, experience a drop in blood glucose. During these times, the -cells release glucagon, which stimulates the liver to make glucose by glycogenolysis and gluconeogenesis, and thereby raise blood glucose to normal levels.
References:
Langley, L.L. (Ed.). (1973). Homeostasis: Origins of the Concept. Langley, National Library of Medicine. Stroudsburg, PA:Dowden Hutchinson, and Ross Inc.
Sherwood, Lauralee. (1997). Human Physiology: From Cells to Systems (3rd ed.). West Publishing Co.
Higher Blood Glucose
Food 56

57. Type 1 Diabetes Mellitus
Normal Glucose Metabolism
Type 1 Diabetes
High blood glucose
High blood glucose
beta-cells destroyed by autoimmune reaction
Blood glucose remains high
Detected by beta-cells
Detected by beta-cells
beta-cells release insulin
beta-cells release insulin
These steps do not happen because the beta- cells have been destroyed
Type 1 Diabetes Mellitus
This diagram shows where in the glucose metabolic pathway Type 1 diabetics differ from healthy individuals.
Type 1 diabetes is an autoimmune disorder, meaning the body’s immune system is not functioning properly and attacks the body itself. In Type 1 diabetes, the antibodies produced by the immune system bind to the beta-cells, which then are destroyed by specialized immune cells. Because the -cells are destroyed, no insulin is produced, and therefore, the peripheral tissues (muscle and fat) do not receive a signal that allows for glucose uptake. Ultimately, this condition causes glucose levels in the bloodstream to remain high. Individuals with Type 1 DM are dependent on exogenous (produced outside the body) sources of insulin.
References:
Langley, L.L. (Ed.). (1973). Homeostasis: Origins of the Concept. Langley, National Library of Medicine. Stroudsburg, PA:Dowden Hutchinson, and Ross Inc.
Sherwood, Lauralee. (1997). Human Physiology: From Cells to Systems (3rd ed.). West Publishing Co.
Peripheral cells respond to insulin by taking up glucose
Peripheral cells respond to insulin by taking up glucose
Lower blood glucose
Lower blood glucose 57

58. Blood sugar regulation Animations/ Tutorials

59. 6.5.12 Distinguish between type I and type II diabetes. (2)
Type I diabetes (early or juvenile onset):
Auto-immune disease in which the beta-cells pancreatic are destroyed.
Unable to produce insulin.
Responds well to regular injection of insulin probably manufactured as the genetically engineered humulin.
Type II diabetes (Adult onset):
Reduced sensitivity of the liver cells to insulin.
Reduced number of receptors on the liver cell membrane. 
In both types of diabetes there is:
a build of glucose in the blood stream and it will then subsequently appear in urine.(test with a Clinistic )
High concentrations of blood glucose (hyperglycaemia) results in the movement of water from cells by osmosis.
This extra fluid in the blood results in larger quantities of urine production.
A lack of glucose in cells means that fats then proteins have to be metabolised in respiration.
Particularly the breakdown of protein for energy creates organ damage.

60. Glucose Homeostasis Research Timeline
1552BC
1st Century AD
1776
18th Century
1869
1889
1983
2001
1552 BC: Ebers Papyrus in ancient Egypt. First known written description of diabetes.
1st Century AD: Arateus — “Melting down of flesh and limbs into urine.”
1776: Matthew Dobson conducts experiments showing sugar in blood and urine of diabetics.
Mid 1800s: Claude Bernard studies the function of the pancreas and liver, and their roles in homeostasis.
1869: Paul Langerhans identifies cells of unknown function in the pancreas. These cells later are named “Islets of Langerhans.”
1889: Pancreatectomized dog develops fatal diabetes.
1921: Insulin “discovered” — effectively treated pancreatectomized dog.
1922: First human treated with insulin. Eli Lilly begins mass production.
1923: Banting and Macleod win Nobel Prize for work with insulin.
1983: Biosynthetic insulin produced.
2001: Human genome sequence completed.
Glucose Homeostasis Research Timeline
George Ebers found the Ebers Papyrus in Egypt in The papyrus is the first known written description of diabetes, and while it is dated to 1552 BC, it contains references contained that date to earlier than 3000 BC. In the 1st Century AD, Arateus famously explained diabetes as the “melting down of flesh and limbs into urine.” Early physicians understood that polyuria (frequent urination) was a symptom of diabetes, but it was not until 1776 that Matthew Dobson was able to show that the sweet taste of a diabetic’s urine was attributed to glucose in the urine.
The “Experimental Period” of diabetes began in the mid-19th Century. The efforts of Claude Bernard, who studied the workings of the liver and pancreas in digestion; the identification by Paul Langerhans of cells of unknown function residing within the pancreas (later called “Islets of Langerhans”); and the pancreatectomy of a dog that resulted in fatal diabetes greatly expanded the understanding of diabetes and glucose homeostasis.
Research continued, and in 1921, insulin was used successfully to treat a pancreatectomized dog. The next year, a 14-year-old diabetic boy also was treated successfully with insulin. This resulted in the Nobel Prize for Medicine for Frederick G. Banting and John James Richard Macleod (both from the University of Toronto). Banting shared his monetary prize with his 22-year old research assistant, Charles Best. Macleod shared his winnings with a biochemist, James Collip. With the advent of molecular biology, research in diabetes led to new pharmaceutical approaches to treatment. In 1983, the first biosynthetic insulin became commercially available, increasing supply and making production relatively cheap, compared to harvesting insulin from pigs and cows. Then, in 2001, the initial draft of the Human genome sequence was completed. This detailed knowledge of man’s genetic composition is leading to new discoveries, but with the complex nature of diabetes (multiple genes, environmental component), the disease still remains largely a mystery.
References:
Langley, L.L. (Ed.). (1973). Homeostasis: Origins of the Concept. Langley, National Library of Medicine. Stroudsburg, PA:Dowden Hutchinson, and Ross Inc.
Sherwood, Lauralee. (1997). Human Physiology: From Cells to Systems (3rd ed.). West Publishing Co. 60

61. Current/Future Research in Diabetes
Clinical Trials: physiological traits of patients/response to therapeutics
Genetic Approaches: candidate genes; family-based studies; genome-wide scans
Animal Models: developing gene-knockout models; large-scale mutagenesis studies to produce diabetic phenotypes
Microarray Analysis: analysis of gene expression in tissues
Future
Continued utilization of human genome sequence data
Sequencing multiple ethnicities
Beta-cell transplantation
Use of stem cells to halt or reverse symptoms
Current/Future Research in Diabetes
Currently, there are two major places in which researchers are studying diabetes and its treatment: the clinic and the laboratory. Clinical trials involve physicians treating patients, and then studying how patients respond to medicines and treatments. Typically, clinical trials involve many affected and unaffected individuals; they are time consuming. However, clinical trials also are a continuous source of new insights into metabolic disorders.
Laboratory scientists are utilizing many approaches to studying disease. Genetic approaches include, but are not limited to, studying candidate genes (genes in a particular pathway implicated in disease); family-based studies in which geneticists trace the inheritance of disease alleles; and genome-wide scans. Genome-wide scans are labor-intensive assays that study biomarkers across the entire human genome. The goal is to locate markers that associate only with disease or unaffected populations.
Animal models are used extensively in the study of disease. Mouse knock-outs (a particular gene of interest is missing) provide valuable insights into the functional properties of gene products (proteins). Large-scale mutagenesis strategies tend not to be directed, but if a particular phenotype of interest is generated, researchers can work back to the disease-causing genotype. Finally, microarrays can examine the expression of all genes in a given tissue in one experiment – thereby generating a tremendous amount of data. Genes that are expressed in healthy individuals but not in affected individuals (and vice versa) are of much interest.
With the generation of the human genome sequence, research into complex diseases is progressing rapidly and beginning a new phase of high-throughput, high-yield data generation. Use of these data to resequence known disease genes or plausible candidate genes is advancing research daily. Furthermore, as sequencing technologies become more ubiquitous, we are quickly approaching a time when DNA will be sequenced in a physician’s office and the molecular diagnosis will allow more effective treatment. This is a goal of “personalized-medicine.”
Finally, the clinic also is progressing, thanks to all the new technologies available. One technology generating much excitement in the field of diabetes research is -cell transplantation. Infusion of healthy -cells into severe diabetics has been shown recently to enhance the patient’s ability to manage his/her disease drastically.
Although there has been much progress, much is left to learn. With all of the new technologies and increased emphasis on biological research, we still find ourselves in the midst of a diabetic epidemic that will affect an estimated 300 million people by the year Furthermore, there is an alarming increase in the number of diabetic children, which correlates to the increase number of obese children in the U.S. Technology and research will continue to advance and shed light on the genetic causes of disease. However, the diabetic epidemic will be reduced only if these advances are combined with healthy lifestyles.
References:
Langley, L.L. (Ed.). (1973). Homeostasis: Origins of the Concept. Langley, National Library of Medicine. Stroudsburg, PA:Dowden Hutchinson, and Ross Inc.
Sherwood, Lauralee. (1997). Human Physiology: From Cells to Systems (3rd ed.). West Publishing Co. 61