Part 2: Glucose Regulation

Endocrine System

Glucose in Blood

Glucose is an important fuel for cellsPancreas maintains blood glucose

levels by secreting hormones

Pancreas Exocrine

system: secretion of hormones through ducts

Exocrine cells: 98%-99% of

pancreas by mass

Produce digestive enzymes released into small intestine

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PancreasEndocrine

cells: 1%-2% of

pancreas by mass

Scattered throughout the pancreas

Islets of Langerhans

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Islets of Langerhans Alpha cells:

secrete glucagon

Beta cells: secrete insulin

Insulin and glucagon are antagonistic hormones

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Insulin Stimulant:

Blood glucose level rises above a set point Observed naturally after eating a meal

Effect: Uptake of glucose by body cells through

facilitated diffusion by activating glucose transporters Inhibits the liver's breakdown of glycogen Inhibits liver’s conversion of amino acids and glycerol

to glucose Result:

lowering blood glucose level decrease stimulus for insulin release

GlucagonStimulant:

Lowered blood glucose Glucose cleared from the blood stream

Effect: Liver to increase breakdown of glycogen Liver convert amino acids and glycerol to

glucoseResult:

Higher blood glucose level Decrease stimulus for glucagon release

Insulin Function

When is insulin released? after eating hyperglycemia

beta cells cellular signals for insulin release

decreased blood sugar

increased glucose uptake

glycogen production in liver

Glucagon Function

What does glucagon do? breaks down glycogen

hypoglycemia

alpha cells cellular signals for glucagon release

increased blood sugar

glucose release from liver

glucose production in liver

Comparing Insulin & GlucagonCharacteristics

Insulin Glucagon

SituationStimulant: Blood glucose levelsEffect: Glucose uptakeEffect: Glycogen breakdown

Comparing Insulin & GlucagonCharacteristics

Insulin Glucagon

Situation After a meal Between meals

Stimulant: Blood glucose levelsEffect: Glucose uptakeEffect: Glycogen breakdown

Comparing Insulin & GlucagonCharacteristics

Insulin Glucagon

Situation After a meal Between meals

Stimulant: Blood glucose levels

Increased

Effect: Glucose uptake

Increase

Effect: Glycogen breakdown

Decrease

Comparing Insulin & GlucagonHormone Insulin GlucagonSituation After a meal Between

mealsStimulant: Blood glucose levels

Increased Decreased

Effect: Glucose uptake

Increase Decrease

Effect: Glycogen breakdown

Decrease Increase

Diabetes Mellitus Cause Decreased insulin levels

Type 1 diabetes: Immune system attacks insulin producing cells

Type 2 diabetes: reasons not related to autoimmunity

Type 2: diabetes: Decreased responsiveness of cells to insulin Inability of insulin to regulate blood glucose

levels Impairment of ability to remove glucose

from the bloodstream

Diabetes Mellitus Types

Type 1(Insulin dependent)

Type 2(Non-insulin dependent)

Onset Childhood Adult (past age 40)Pregnancy

MolecularCause

Insulin deficiency Insulin resistance (unresponsive receptors) and deficiency

Cause GeneticAutoimmune disorder

Obesity

Treatment

Daily insulin injections

Exercise & dietary control drugs

Diabetes Mellitus Effect Glucose unavailable to body cells

Hyperglycemia: high glucose in blood Excessive hunger Fat used for cellular respiration Increased blood viscosity and decreased blood flow

▪ leads to blurry vision (poor blood flow in capillaries of retina)

▪ foot infections (gravity cause blood to pool in feet) Kidneys start to excrete glucose

Glucosuria: glucose in urine, “sweet” urine Frequent urination Persistent thirst

Diabetes Insipidus Cause Inability of kidneys to conserve

waterCause: deficiency in ADH

ADH controls excretion rate by reabsorbing water from urine into blood

Diabetes Insipidus SymptomsExcessive thirst Frequent urinationDilute urineUrine does not contain glucose and

is not sweet

Diabetes Insipidus TreatmentDrinking sufficient waterTake ADH medication

Canadian Connection Frederick Banting &

Charles Best Nobel Prize – 1923 insulin isolation

tied off ducts to digestive tract

cell producing digestive enzymes shrivelled

only islets of Langerhans remained

Banting and Best Banting and Best began their experiments

by removing the pancreas from a dog. This resulted in the following: It's blood sugar rose. It became thirsty, drank lots of water, and

urinated more often. It became weaker and weaker. The dog had developed diabetes.

They then isolated “insulin” and injected it back into the dogs and they seemed to be cured.

Leonard Thompson January

1922 in Toronto, Canada

14-year-old boy was the first to be treated with insulin injections

Stress Regulation

What is Stress? The feeling of alarm or distress when

reacting to particular eventCan be physical, emotional, cognitive

or mental

Stress Response

Natural responsePrepares an individual to handle the

stressor (an event that provokes stress)

Types: Short term: responses are immediate Long term: responses are ongoing and

can cause detrimental side effects on the individual

Adrenal Gland

Secretes stress response hormonesLocation: adjacent to kidneysStructure:

Adrenal cortex : outer portion, involved with long-term stress response

Adrenal medulla : inner portion, involved with short-term stress response

Short Term Stress Response

Short-term Stress ResponseStress excites nerve

cells to release a neurotransmitter: acetylcholine (ACh)

Stimulates adrenal medulla to release catecholamines: epinephrine and norepinephrine

Catecholamines

Synthesized from tyrosineSecreted in response to positive or

negative stress by the adrenal medulla

Types: Epinephrine (adrenaline) Norepinephrine (noradrenaline)

Tyrosine

Catecholamines

Effects

Stimulates the “fight-or-flight” response

Increase metabolism Cellular respiration produces ATP Need oxygen Need energy source (glucose)

Effects: Energy Source

Increased blood glucose levels Glycogen glucose more ATP readily available

Stimulates the release of fatty acids from fat cells to supply the body with more energy

Decreased kidney and digestive activity

Effects: Oxygen

Increased blood pressure and blood flow oxygen is distributed to cells faster

Increased breathing rateRelaxes/contracts certain blood vessels

overall effect of redirecting blood away from non-vital areas

increasing blood flow to the heart, brain, and skeletal muscles

Increased alertness

Application

Epinephrine is present in epinephrine autoinjectors (EpiPens)

Long Term Stress Response

Long-Term Stress Response: Neuroendocrine pathway CRH

ACTH Corticosteroid

Glucocorticoid Mineralcorticoid

Long-Term Stress Response: Neuroendocrine pathwayLocation Hormone

Stimulus StressHypothalamus Corticotropin-releasing

Hormone (CRH)Anterior Pituitary

Adrenocorticotropic Hormone (ACTH)

Adrenal Cortex

Corticosteroids:Glucocorticoids (e.g. cortisol)Mineralocoritcoids (e.g. aldosterone)

Effect Increase glucose productionIncrease oxygen delivery

Corticotropin-Releasing Hormone (CRH)Neuropeptide hormoneReleased from hypothalamus Cause: stressful stimuli Stimulates anterior pituitary to

synthesize ACTH

Adrenocorticotropic Hormone (ACTH)Polypeptide hormoneTropic hormoneProduced from anterior pituitaryStimulates adrenal cortex to

synthesize corticosteroids

Corticosteroids steroids produced and released from the adrenal cortex

Type ExampleGlucocorticoid Cortisol

Mineralcorticoid Aldoesterone

Sex hormones testosterone

GlucocorticoidsEffects: Energy sourceAffects glucose metabolism

Synthesize of glucose from non-carbohydrate sources

Liver breaks down muscle protein in skeletal muscles to glucose

Occurs when body needs more glucose than what the liver can produce from its storage of glycogen

MineralocorticoidsEffects: Indirectly on oxygenHormone that affects the body’s

osmotic balance Stimulates reabsorption of salt and

water by kidneysCause increase in blood volume and

pressure Increase oxygen delivery

Compare Short & Long Term Stress Management

Stress Short term Long termHormones

EpinephrineNorepinephrine

Glucocorticoid (cortisol)Mineralcorticoid (aldoesterone)

Energy Glucose from glycogen stores

Glucose from non-carbohydrate source

Oxygen Increase heart rate, pressure, flow & resp rate, regulate vessel size

Increase reabsorption of salt and water, blood volume, pressure & flow

Stress Associated Disorders

Hypersecretion: Cushing’s DiseaseOverproduction of corticosteroids

(glucocorticoid) Cause: pituitary tumour (excess

ACTH)Treatment: surgery, radiation

Cushing’s Disease Effects Mimic diabetes:

Hyperglycermia (high blood glucose) Glucosuria (glucose in urine) Protein shortage (protein converted to glucose)

Physical effects: Excess glucose deposited as body fat in

abdomen, face, above shoulder blades▪ Weight gain, “moon face” and “buffalo hump”

Appendages remain thin Muscle weakness, prone to bruising Weak skeleton, prone to fractures

Hyposecretion: Addison’s DiseaseFailure to produce adequate levels of

glucocorticoid (cortisol) Cause: autoimmune / adrenal gland

disorders immune system gradually destroys the

adrenal cortexTreated with

gluco/mineralocorticoids

Addison’s Disease Symptomsmajor weight lossdizziness, vomiting and nausea extreme pain in stomach