Note
Studied by 28 people
Bio 120 Modules 5 + 6
Blood Sugar on the Rise: What is diabetes mellitus and why is it a major public health concern?
Chemical messengers and the endocrine system
General Categories of Chemical Messengers (short distances)
Autocrine secretion- chemical messenger affects cell that secreted it (extra local)
Paracrine Secretion- chemical messenger secreted by one cell and affects nearby cell
Neurotransmitters- chemical messenger secreted by neurons @ synapses
“Endocrine” secretions travel through the blood to affect distant cells
Endocrine Secretion- “hormone,” secreted into blood, affects distant cells (long distant messengers). These hormones play crucial roles in regulating various physiological processes, including metabolism, growth, and mood.
Neuroendocrine Secretion- “neurohormone”, neuron secretes chemical messenger into blood, affects distant cells
Hormones and Receptors
A focus on endocrine secretions: general features
Gland- ductless, rich blood supply
Hormone- secreted into the blood
Transport- reaches every cell in the body (does not mean all cells are affected)
Target Cell- only cells affected by hormones
Three Main Chemical Types of Hormones
Peptide/Polypeptide/ “Protein Hormones”: Composed of amino acids, these hormones are water-soluble and cannot easily cross cell membranes, thus they bind to receptors on the surface of target cells. Most abundant type, tends to be species specific. Made via gene expression transcription-translation
Steroid Hormones: Derived from cholesterol, these fat-soluble hormones can pass through cell membranes and bind to intracellular receptors, influencing gene expression directly. There are 5 classes with it being not being species specific
Amine Hormones: These are derived from amino acids and can be either water-soluble or fat-soluble, depending on their specific structure.
Hormones must interact with a receptor to exert an effect.
Receptors are specific
2 General classes of receptors
Membrane Bound Receptors (signal transduction or signal amplification and hormone never enters the cell) and Intracellular Receptor (changes in cell are slower than in membrane receptor activation)
Membrane receptor activations leads to rapid changes in cells with most of the time ATP being required for signal amplification
Hormone receptor complex acts as a gene transcription factor
More mRNA transcripts are produced and each transcript is translated many times…both examples of signal amplification
“Mechanism of Action”- how a receptor works to effect change in cell
Peptides+ Polypeptides- cannot cross membrane (polar + charged)
Amino Acid Derivatives- most cannot cross (polar)
Steroids- can cross/are lipid soluble
Membrane Receptors (polypeptides + peptides/amino acid) and Intracellular Receptor (Steroids)
Glucose Homeostasis
Glucose: if too low= hypoglycemic→ not enough fuel to produce ATP, if too high= hyperglycemic→ high glucose levels, toxic to neurons and blood vessels
Insulin + Glucagon: 2 pancreatic hormones that are important in maintaining glucose homeostasis
Pancreas is an endocrine organ: secretes hormones (not thru ducts), exocrine organ- secretes digestive enzymes (thru ducts)
Islets of Langerhans= Pancreatic Islets
Alpha Cell → glucagon Beta Cell→ insulin
Glycogenesis: The process by which glucose molecules are linked together to form glycogen, which is stored primarily in the liver and muscle cells. This process occurs when glucose levels in the blood are high, allowing the body to store excess glucose for future energy needs.
Glycogenolysis: The process by which glycogen is broken down into glucose, allowing for the release of glucose into the bloodstream when blood sugar levels are low. This is crucial for maintaining glucose homeostasis in the body.
Recall: lipid bilayers are selectively permeable
Glucose Transporters (GLUT transporters)- membrane proteins that allow glucose to cross membrane
Facilitated Diffusion- diffusion of substances across membrane with assistance of protein transporter/channel
Some are not regulated: always present in membrane (no special signal required to insert in membrane) GLUT 1, GLUT 2, and GLUT 3
GLUT 1- most cells in body, GLUT 2- abundant in liver cells, GLUT 3- abundant in CNS
Others are regulated: they require a signal to be inserted in the membrane.
GLUT 4
pool of vesicles inside of the cell containing GLUT 4 transporters
insulin binds receptor receptor, stimulates insertion of GLUT 4 transporter into membrane
GLUT 4 is insulin regulated
found in skeletal muscle cells and adipose (fat) cells
Insulin stimulates uptake glucose by cells
Insulin has important actions in liver, adipose, and skeletal muscle tissue
Insulin Action on Liver Cells
glucose uptake occurs through GLUT 2 transporters (non insulin regulated)
insulin binds receptors on liver cells, signal transduction stimulates glycogenesis (formation of glycogen)
glucose is also metabolized here to produce ATP
Insulin Action on Skeletal Muscle Cells
most abundant glucose transporter= GLUT 4 (insulin dependent)
insulin stimulates insertion of GLUT 4 into membrane
glucose → ATP
other actions of insulin @ muscle cells
glycogenesis (formation of glycogen)
stimulates protein synthesis w/ amino acid uptake into muscle cells
Insulin Action on Adipose Tissue Cells
insulin binding to receptor stimulates insertion of GLUT 4 transporters into membrane
insulin also stimulates formation of glycerol and uptake of fatty acids.. overall triglyceride production
Diabetes mellitus is a disorder of glucose regulation
Type 1 Diabetes: individual doesnt secret sufficient insulin to stay in glucose homeostasis, * Beta cells of pancreas are attacked by immune system → no insulin
Type 2 Diabetes: target cells don’t respond properly to insulin → receptor issue, “insulin resistance” *origins: lifestyle factors (diet, exercise, etc) + genetic predisposition (Major Public Health Concern)
Type 2 Diabetes Risk Factors
obesity
high sugar diet
lack of exercise
metabolic syndrome
What are the consequences of chronic hyperglycemia?
Marcovascular complications (effects on arteries)
Glycoslyation- glucose binds to proteins in the blood
Atherosclerosis- thickening, hardening of arteries due to build up of plaques, *reduced blood flow, can lead to heart attack, stroke, coronary heart disease, peripheral artery disease (extremities don’t get blood supply)
Mircovascular complications (problems w/ capillaries)
Diabetic nephropathy- kidney disease, problems w/ capillaries and filtration, damage to capillaries in kidneys
Diabetic retinopathy- problems w/ capillaries can lead to blindness, disease of the retina, vision problems due to damage of capillaries at the retina
Neuropathy (problems with neurons)
Diabetic neuropathy- problems w/ neuronal communication, nerves shrivel when blood vessels disappear due to the reduced blood flow. * loss of sensation and greater likelihood of injuries that may be unnoticed
What are the most common treatment approaches?
pharmaceuticals- drugs that attempt to mitigate certain aspects of disease, increases cellular responsiveness to insulin and insulin production. e.g. metformin, GLP-1 agonists, sulfonoureas
lifestyle changes- diet, exercise
Why is diet important? foods you eat determine how much glucose is in your blood which impacts insulin production
Why is exercise important? GLUT 4 receptors: exercise stimulates insertion in the membrane too.
GLUT 4- skeletal muscle tissue, GLUT 4 is abundant, regulated insulin and muscle contraction
Living Life in the Clear: How can Antarctic icefish survive without red blood cells?
What is blood useful for?
gas transport (O2 , CO2)
fighting infections, coagulation/clotting
transport of heat
transport of waste
transport of hormones
nutrient transport
Which blood gases are most important? O2 , CO2
Cellular Respiration: C6H12O6 + 6O2 ——→ 6CO2 + 6H2O + ATPs + Heat
Red Blood Cells, Respiratory Pigments, and Physiological Functions
Whether fish or human, gas exchange occurs at the respiratory surface which is characterized by thin membrane and lots of capillaries (allows for efficient gas exchange)
Recall: lipid bilayers are selectively permeable
Gases are diffusing across membranes (based on concentration gradients)
Red Blood Cells and Respiratory Pigments
Erythrocytes (45% of total blood) → Hematocrit= 45
Blood can carry way more O2 than what is simply dissolved
Each red blood cell contains several hundred million hemoglobin (respiratory pigment) molecules which transport oxygen
Respiratory pigments bind O2 reversibly
Hemoglobin (Hb)
4 subunits
protein portion- “-globin”
heme portion- iron containing
each subunit can bind 1 O2
cooperative binding: when 1 O2 binds, Hb has a conformational change that increases likelihood of more O2 binding
O2 dissolves into blood plasma→ enters red blood cells, binds to Hb (now it is taken out of solution → not containing to concentration)
majority of O2 binded to Hb
Hb binds to oxygen reversibly: Hb + O2 —> HbO2
what happens when O2 concentration is high? When O2 concentration is high, hemoglobin (Hb) has a higher likelihood of binding to oxygen due to cooperative binding. This means that as one O2 molecule binds to hemoglobin, it induces a conformational change in the hemoglobin structure that increases the affinity for additional O2 molecules to bind. This process helps in efficiently transporting oxygen from the lungs to the tissues that require it.
what happens when O2 concentration is low? When O2 concentration is low, hemoglobin (Hb) exhibits decreased binding affinity for oxygen. This means that hemoglobin will release oxygen more readily into the tissues that require it. The reduced availability of oxygen stimulates mechanisms in the body to increase oxygen delivery, such as increased heart rate and respiratory rate, and can also trigger the production of red blood cells by stimulating erythropoietin from the kidneys.
The amount of O2 blood to the Hb depends on how much O2 is dissolved in the blood plasma→ concentration of dissolved O2 in plasma → partial pressure of O2 = PO2
O2 saturation (%) of Hb ← % of Hb binding sites bound
PO2 ← amount of O2 dissolved in blood plasma
Cooperative binding- when 1 O2 binds to Hb, the other binding sites bind O2 more readily (conformational change)
Where in body is PO2 low?- anywhere in the body that isn’t the respiratory surface or the lungs
Where in the body PO2 high? - respiratory surface + the lungs
General Principle Alert: Tradeoffs: b/n loading of O2 onto Hb @ respiratory surface and unloading (‘delivery’) of O2 from Hb @ systemic tissues
Hb’s affinity ( the ease w/ which Hb will bind O2 when it encounters O2) for O2 tells us which one is favored
High Affinity (saturated @ low PO2)- readily binds O2, even when there’s not much available
Low Affinity (saturated @ high PO2)- binds O2 less readily; becomes saturated only when there’s alot of O2 available
P50 is a measure of O2 affinity
higher affinity respiratory pigment has lower P50 value
One more respiratory pigment: Myoglobin (Mb)
single subunit
globin portion (protein)
heme unit (Fe-containing)
very high affinity for O2
only found in muscle cells
skeletal + cardiac muscle
What is function of myoglobin?- O2 reserve “storage” for muscles, holds onto O2, gives it up only when concentration drops very low
Some icefish also lack myoglobin
3 vertebrate circulatory systems: anatomy and function
Atria (plural) ventricles
Fish Heart: 1 circuit, “2 chambered” heart
Closed systems: blood vessels; a) capillaries (gas exchange)are small and extremely thin walled
Dynamics of Blood Flow through the capillaries: slow for gas exchange
Fish Heart: 2 chambers, only pumps deoxygenated blood, 1 ventricle, 1 atrium , relatively low blood pressure
Heart Action: cardiac output= volume pumped per unit time, CO= HR x SV
Loss of Hb in icefish is disadvantageous (Hb loss is considered a disadaptation)
disadaptation- trait that is inferior to ancestral trait
Question 1: How did icefish lose the ability to produce hemoglobin?- loss of genes themselves
globin genes in fish- partial alpha globin gene, no beta globin gene “gene delection”
Question 2: When did loss of Hb genes occur in icefish evolution? 5.5-2 million years ago
loss of functional globin genes: happened 1x in ancestor common in icefish
synapomorphy= shared derived trait
Question 3: If not advantgeous, why did this condition persist?
cold H2O- higher O2 content
well aerated (always moving, distributed)- higher O2 content
cold H2O lowers MR of icefish (lower O2 demand)
lack of competition → many species that lacked sufficient antifreeze protein production disappeared when ocean cooled
Hb loss = sublethal trait (only disadvantageous in the context of competition)
Icefish have a low thermal tolerance compared to red blooded fish
Learning Objectives
Identify features of the diabetes mellitus epidemic.
Explain what makes a chemical messenger a “hormone”, and
how hormones differ from other types of chemical messengers.
Explain the differences among steroid, protein, and amino acid
derivative (i.e., modified amino acid) hormones
Understand differences between membrane-bound and
intracellular receptors (including their location in/on the cell and
their function when activated).
Identify the general properties of hormone receptors; understand how
the mechanisms of action differ for intracellular vs. membrane-bound
receptors.
Describe how the interplay of insulin and glucagon secretion and
action regulate blood glucose homeostasis in mammals. Know what
stimulates release of each hormone, the cell types they’re secreted
from, and explain how each hormone affects blood glucose levels.
Describe how alterations in insulin secretion and/or action would
affect blood glucose levels.
Explain the concept of facilitated diffusion and the role that
membrane proteins play in facilitated diffusion of glucose
across cell membranes.
Explain the difference between glucose transporters that are
regulated by specific signals (e.g., GLUT4) and those that are
not regulated by specific signals (e.g., GLUT1, GLUT2, GLUT3).
Articulate specific actions of insulin on liver, skeletal muscle,
and adipose tissue cells.
Differentiate between type I and type II diabetes mellitus.
Explain what is meant by“insulin resistance” in type II diabetes and
explain what this means from an endocrine signaling perspective.
Describe the physiological and health consequences of chronic
hyperglycemia, as is seen in type II diabetes.
Identify the primary treatment approaches to type II diabetes and
explain why exercise is particularly helpful for regulating blood
glucose.
Describe the physiological and health consequences of chronic
hyperglycemia, as is seen in type II diabetes. (From Monday)
Identify the primary treatment approaches to type II diabetes and
explain why exercise is particularly helpful for regulating blood
glucose. (From Monday)
Describe some physiological features that make Antarctic icefish
unique among vertebrates.
Identify general functions of blood and, in particular, red blood cells.
Describe the importance of respiratory pigments in oxygen
transport.
Understand what dictates the shape of a hemoglobin-oxygen
equilibrium curve.
Explain what is meant by hemoglobin’s oxygen affinity and draw a
hemoglobin-oxygen equilibrium curve that illustrates hemoglobin
with a high affinity for oxygen and one that illustrates hemoglobin
with a low affinity for oxygen.
Explain how myoglobin differs from hemoglobin, where it is found,
and what its function is.
Describe the major vessels found in closed circulatory systems,
and understand how they differ in form and function from one
another.
Explain the significance of the large cross-sectional area and low
velocity of blood flow found in blood capillaries.
Understand what cardiac output is and what affects it.
Explain how icefish globin genes differ from those found in other fish
and describe the point at which the ability to synthesize hemoglobin
was lost in icefish evolutionary history.
Explain and provide evidence for physiological compensation
mechanisms that allow icefish to survive without hemoglobin.
Understand the importance of specific features of the Antarctic
habitat in icefish evolution and explain why the icefishes’ unique
physiological characteristics have persisted through evolutionary time.