Basics of Insulin & glucose

Too much glucose =

hyperglycemia (aka high blood sugar)

Too little glucose =

hypoglycemia (too little blood sugar)

If we have too little of a hormone we give?

a synthetic version of the hormone or a drug that increases the stimulation of the organ to produce more endogenous hormones

Endocrine organs __________& __________hormones

synthesize and secrete

Endocrine means:

hormones released into the bloodstream affecting many different types of tissue

• (insulin, epinephrine, NE are all examples of hormones that affect different tissues and organs)

Paracrine means:

hormones that are released into adjacent (neighbouring) tissues only

What are examples of paracrine hormones?

• histamine ==> secreted IN tissues and present in tissues

  • Histamine doesn’t circulate, it stays a local hormone

Endocrine hormones typically have a _____half life d/t kinetics

long ==> likely highly PPB (plasma protein bound)

What’s an example of a hormone with a long ½ life?

T4 = the thyroid hormone

What triggers secretion of hormoned?

• concentration of specific substances (ex: high glucose causes the pancreas to release insulin)

• neural stimulation via. SNS ==> epinephrine

• Endocrine sequences (epinephrine ==> aldosterone); such as the BP sequences where something is in deficit so we work backwards in sequence to see where the glitch is

How do we sometime get a diagnosis of what hormone is “glitching”?

by working/testing the endocrine sequences to see where it’s going wrong

How does NE trigger aldosterone release?

1. SNS activation: A drop in blood pressure or blood volume causes increased sympathetic nerve activity, leading to the release of NE.

2. Renin release: NE stimulates beta-1 adrenergic receptors on the juxtaglomerular cells in the kidneys, prompting the release of renin into the bloodstream.

3. RAAS system end product is aldosterone which induces salt absorption where water follows and raise the BP that way

What mechanism regulates the endocrine system?

Mostly negative feedback:

• we have too much of something, we turn it off

• we have too little of something, we increase the production

What substance tests insulin function?

Glucose

How do we test the functions of endocrine organs to see if they’re secreting hormones properly?

• by testing the level of substance it produces or measuring the hormone levels

• Ex: test insulin by checking glucose ==> indirect test

• test thyroid hormone levels by checking the T4 hormone ==> direct test

How do we test for congenital endocrine errors?

Via. blood test which is sent for 21 different tests before the baby is even born

What are the dysfunctions of the endocrine system?

• hyposecretion & hypersecretion

  • d/t primary endocrine disorder; signaling disorder; sequence disorder

What are some causes for hyposecretion of a hormone?

• congenital defects

• disease/infection/inflammation

• hypoperfusion (severe MI, CO decreased, aging)

What are some causes for hypersecretion of a hormone?

• genetics

• tumors

• environmental stimuli

The s&s will be directly related to excess or deficit of the expected hormone level:

hypoperfusion = deficit in _________________

hyper functional = opposite ==> too efficient

functionality

What are some of the glands of the endocrine system?

• hypothalamus ==> anterior and posterior pituitary glands

• pineal gland ==> sleep hormone 

• Thyroid and parathyroid

• thymus

• Pancreas

• ovary

• Adrenal glands

• Placenta

What are the 2 main primary energy sources for the body?

glucose, fatty acids (fat)

Glucose is readily distributed and most needed by the _______

CNS ==> brain

• it requires a constant supply of glucose

  • this is then broken down into CO2 and H20

What does the brain use to survive if glucose isn’s available?

It uses ketones

you CANNOT store glucose for later, true or false?

False!!, you CAN store extra glucose

what happens with the extra glucose?

it turns into glycogen stored in the liver and muscles and as triglycerides (in adipose/fat tissue).

Extra glucose is turned into:

A. Glycogen (short-term storage)

• Stored in liver and muscles.

• When blood sugar drops → body breaks down glycogen via glycogenolysis (triggered by glucagon).

B. Triglycerides (long-term fat storage)

• Stored in adipose (fat) tissue.

If glucose is low for a long time:

Body makes new glucose from non-carbs through gluconeogenesis (proteins, glycerol, lactate, etc.).

What happens when there’s a drop/fall in blood glucose?

Glycogen gets broken down via. “glycogenolysis” into glucose again

What triggers the breakdown of glycogen into glucose again?

The hormone glucagon, it stimulates the body to break down glycogen

What is gluconeogenesis?

Formation of more glucose from other sources that’s released as needed

What happens to fatty acids after they’re digested in the small intestine?

They’re distributed via lymph as chylomicrons into circulation and travels to the right atrium

_______ and _________can’t use fatty acids

CNS & Red blood cells can’t use fatty acids

• hence why we don’t store fat in the brain

What happens when the body breaks down triglycerides?

Extra fat/FA is stored as triglycerides and can be broken down into 3 fatty acids + glycerol

Fatty acids are NOT easily converted into glucose - cannot be used by the ___________ for energy

brain

What does the body do when glucose is low, aka. when someone is fasting?

When glucose is low (fasting, starvation, low-carb diet):

• Liver breaks fatty acids into ketone bodies

**Ketones can cross into the brain and be used for energy

This is what happens in ketosis.

What provides glucose movement into cells and out of circulation?

Insulin

Summary:

Glucose and fatty acids are the main sources of energy

Glucose gets turned into glycogen or fat

Fat is turned into triglycerides

What is insulin?

• A pancreatic hormone produced by the beta cells (β-cells) in the islets of Langerhans.

• Released when blood glucose is high (like after eating).

What are the main job of insulin?

1. Helps glucose enter cells

👉 “Glucose’ cellular uptake”
Insulin acts like a key that unlocks cells so glucose can enter and be used for energy.

Insulin also tells the body to __________energy and not break it down

store

It increases:

• Glycogen synthesis (stores glucose in liver & muscle)

• Triglyceride synthesis (stores fat in adipose tissue)

• Protein synthesis (builds muscle & tissues)

Insulin prevents:

• Glycogen breakdown

• Fat breakdown

• Protein breakdown

Because the body wants to use glucose first, not burn stored energy

Insulin helps ___________also enter cells, not just glucose

amino acids enter cells

→ Supports protein building
→ Helps triglycerides enter fat cells for storage

Insulin = anabolic hormone (“builds & stores”).

3 actions of insulin?

• glucose celular uptake

• promotes storage formations > glycogen synthesis, triglyceride synthesis and protein synthesis. > insulin stores glycogen, triglycerides and protein

• Amino acid cellular uptake

Where is Glucagon (hormone) synthesized/made?

• in the alpha cells

• It is the opposite of insulin.

Released when:

• Blood sugar is LOW

• Between meals

• During hypoglycemia

Where does insulin and glucagon come from?

Insulin and glucagon come from specific cells in the pancreas

• Beta (sweet) cells create insulin

• Alpha cells create glucagon

• Function: raise blood glucose by releasing stored energy.

What does glucagon do?

Promotes breakdown of stores to release glucose:

• glycogenolysis (glycogen breakdown)

• lipolysis (triglyceride breakdown)

• gluconeogenesis (amino acid conversion into glucose)

What triggers glucagon release?

Glucagon is triggered by low plasma glucose levels (low glucose in blood)

(between meals; hypoglycemia) => leads to mobilizing stores to release more glucose into blood and replenish blood glucose for cellular use

What is glycogen?

• stacks of glucose

• once we run out of glycogen, we start to breakdown other things like protein and blood glucose rises

What is the normal glucose range?

4-8 mmol/L = feeling great

***we often like to see it at 5 in diabetic patients, has to be in range at all times

High blood glucose vs. low blood glucose

blood sugar regulation

• Cells have to uptake glucose via. insulin

What triggers insulin synthesis in the beta cells?

stimulant is high serum glucose

• so high glucose in blood triggers insulin synthesis and secretion

How does glucose enter pancreatic beta cells?

Glucose enters beta cells through glucose transporter

• The glucose is then metabolized via. Glucokinase into ATP

How is insulin released?

Step 1: Glucose (substance) enters beta cells via. glucose transporter

Step 2: Glucose is metabolized via. Glucokinase (enzyme) into G6P

• G6P produces ATP

Step 3: ATP closes K⁺ channels, potassium cannot leave cell

Step 4: Cell depolarizes because cell is positive due to K+

Step 5: insulin is secreted

What happens after to insulin after it’s released from pancreas?

• insulin from pancreas enters hepatic circulation (insulin goes to liver, 50% is metabolized)

• insulin metabolites are renally excreted after metabolization and

  • insulin goes into bloodstream

What is insulin’s action after it’s released into systemic circualtion ?

insulin binds to cell membrane receptor called tyrosine kinase

• > activates kinase enzyme within cell > ==> stimulates glucose transported channels to open to Glucose and take in glucose

Insulin binds to tyrosine kinase ==> Opens up another glucose channel and trickle into that cells

What inhibits Insulin?

Somatostatin (D cell produced)

Absence of glucose shuts down __________

insulin

What’s a lab value that can be a precurssor to diabetes?

Hemoglobin A1C and steroids both can cause diabetes

What happens if the beta cells are destroyed (immediate effect)?

beta cells being destroyed means disabled transport of glucose into cells, because without beta cells you don’t have insulin and you need insulin

==> dysfunction of glucose, fat, & protein metabolism

What is the results of beta cell destruction/side effects?

• hyperglycemia (because glucose stays in blood without insulin)

• High solute (glucose) concentration (polydipsia ==> excessive thirst occurs), so low water and high solute = cells become dehydrated

  • Osmotic shift of fluid into circulation = cellular dehydration

• Polyuria (excessive urination): Osmotic shift into filtrate = high urine production (polyuria stimulated)

Triad of Side effects d/t hyperglycemia

So the classic triad appears:

• Hyperglycemia

✔ Polydipsia

Polyuria

Glycosuria —> glucose in urine and filtrate

With high glucose in blood, it leads to:

Breakdown of triglycerides and fats because the CELLs cannot use glucose despite in being in bloodstream ==> leads to ketones as a byproduct

a metabolic shift to use fat for energy = so breakdown of triglycerides and glycerol

> hepatic (liver) metabolism of fatty acids > ketones (ketone bodies are produced)  because of fat metabolism 

fat metabolism byproducts:

KETONES —> acidic

• ketones accumulate and cause metabolic acidosis (DKA)

As ketones accumulate:

• Blood becomes acidic

• Blood pH drops (below normal 7.35–7.45)

Acetone is volatile → sweet, fruity breath.

What does acetone as a byproduct of DKA cause?

Acetone is volatile → sweet, fruity breath.

Ketones in urine =

ketonuria ==> they start to be excreted so we test for them

What are side effects of DKA?

• changes in LOC (due to acidosis and inability of other cells to function)

• lactate —> lactic acid —> elevates blood acidity

• acetone is exhaled in breath

• coma

• death

When osmotic pressure is called oncotic pressure, its because _________is the influencer

protein

What is the disease name where beta cells are destroyed?

Type I diabetes

Ketone bodies metabolism

Liver

• Makes ketones

• From fatty acids

• Low glucose trigger

What are the consequences of reduced glucose uptake?

glucose is low and we don’t have energy, therefore:

Fat breakdown == ketones

Fat stores are depleted so then: proteolysis (muscle wasting)

• Lipolysis ==> fatty acid breakdown

  • liver metabolism of fatty acids (fatty acid oxidation) ==> ketones and ketonuria

• Depletion of fat stores ==> proteolysis (smooth muscle then gets broken down and functionality decreases = severe effects of weight loss & muscle wasting)

What altered cell functions are seen with reduced glucose reuptake?

• insulin resistance ==> in cells that actually need it because they have decreased functionality, so they got used to not having insulin

• Altered cellular repair 

• endothelial dysfunction and decreased angiogenesis (no new blood vessels)

• increased ROSS > inflammatory response (oxidative particles hurt the cells)> risk for clotting

• organ injury ==> organs will suffer first

Why won’t the cells respond to insulin when we first administer it?

We won’t see immediate results because cells aren’t used to the insulin so when we administer insulin we have to wait a bit to see

What is our #1 priority even before giving insulin?

Restoring normal hydration because the cells are dehydrated d/t high solute concentration

• so rehydrate the cells in order for them to respond to insulin

**-Dehydration and depleted energy led to complete dysfunction of cells