Endocrine Physiology 2 Flashcards
Energy Balance equation
energy intake - energy out
Satiety centre promotes feeling of fullness by suppressing
Feedback centre (insulin sensitive)
Glucostatic Theory
as BG Increases, Drive to Eat Decreases
Lipostatic Theory
As fat stores increase, drive to eat decreases
what type of hormone is leptin
peptide released by fat which depresses feeding activity
What is a Anabolic Pathway
Build up
What is catabolic pathway
Break down
Which part of eating is anabolic?
Absorptive after eating
Which part of eating is catabolic
overnight
between meals
What happens when in post absorptive state to brain?
Maintain BG Concentration or lead to Hypoglycaemia
BG is maintained by synthesising glucose from
Glycogen (Glycogenolysis or Amino Acids (gluconeogenesis)
Normal rate of BG
4.2-6.3
What is hypoglycaemia classified as
<3nm
In diabetes what happens when lose insulin
Glucose can’t be taken up so BG rises and glucose detected in Urine
The brain only has access to BG when
Falls below normal range
99% of pancreas operates as
Exocrine gland releasing enzymes and NaHCo3
Hormones produced by
Islets of Langherhan
How many types of Islet of Langerhan
4
A Islet of Langherhan produces
Glucagon
Beta cells produce what type of insulin
Insulin
alpha cells produce what type of insulin
Alpha cells
f cells produce what type of insulin
Pancreatic Polypeptide
When glucose is taken up by cells from plasma what happens to BG
decreases
In fed state when insulin dominates what happens to insulin
Increased Glucose oxidation
Increased Glycogen Synth
Increased Fat Sync
Increased Protein Synth
In fasted stated when glucagon dominates this leads to
Increased Glyconeolysis
Increased Gluconeogenesis
Increased Ketogenesis
Insulin is what type of hormone?
Peptide Hormone produced by Pancreatic B cells
Insulin does what to glucose?
Stimulates glucose uptake by cells
Insulin is synthesised as
Preprohormone preproinsulin which is converted to proinsulin in ER
Proinsulin is packaged as what in secretory vesicles during synthesis?
Granules where proinsulin is cleaved again to give insulin and c peptide
How is insulin stored?
As C Peptide and Insulin in Granules until B cell activated.
What stimulates insulin secretion? (3)
Glucose
Amino acids
Blood Glucose Concentration
Which hormone dominates absorptive state
Insulin
Which hormone lowers BG
Insulin
Excess glucose is stored where?
As glycogen in Liver and Muscle
As Triglycerols in Liver and Adipose
Fatty acids are stored where?
Triglycerides in Adipose Tissue and Fat
What is sensitive to ATP within cell for B cells
K+ Ion channel sensitive to ATP within cell (KATP Channel)
When glucose is abundant it enters cells through?
GLUT and Metabolism Increases which increases amp within cell = Katp channel closes
When glucose enters cell what happens to intracellular k?
It rises depolarising cell.
Voltage Dependent Ca2+ open and trigger insulin vesicle exocytosis into circulation.
What happens when there is high glucose levels in blood?
- Metabolism Increases
- ATP Increases
- KATP Channels Close
- Cell depolarise and calcium channels open
- Ca2+ entry act as intracellular signal
- Ca2+ signal triggers exocytosis and insulin secreted
What happens when low glucose?
ATP low so KATP stay open so K+ ions flow out removing positive charge from cell and hyperpolarise it so voltage gated Ca2+ channels remain closed/insulin not cleaved
Insulin binds to which receptors?
Tyrosine Kinase Receptors on cell membrane of insulin dependent tissues to increase glucose uptake
What is the only hormone that lowers BG
Insulin
What does insulin do in Muscle and Adipose Tissue
Stimulates mobilisation of specific glucose transporters: GLUT 4 which reside in cytoplasm of these cells
Where does GLUT 4 reside in muscle and adipose tissue?
Cytoplasm
When stimulated by insulin what happens to GLUT4
Migrates to membrane and able to transport glucose into cell.
When insulin stimulation stops what do GLUT 4 transporters do?
Return to cytoplasmic pool
What process allows glucose to enter cells
Exocytosis
What are the only types of tissue that are insulin dependent to take up glucose
muscle and fat
In other tissues glucose uptake is via other GLUT transporters which are not?
Insulin dependent
What allows glucose uptake in many tissues
Brain
Kidney
Red Cells
What allows glucose uptake in pancreas and liver
GLUT 2
B cells
Is the liver insulin dependent
No
How does liver take up glucose
GLUT 2 Transporters
GLUT 2 Transporters are said to be?
Insulin Independent
Glucose enters liver how?
Down concentration gradient
Does insulin have any direct effect on liver?
No
Glucose transport into where in liver is affected by insulin status
Hepatocytes
In fed state liver takes up glucose because
Liver activates Hexokinase which lowers glucose moving glucose into cells
In fasted state liver synthesises glucose via
glycogenolysis and gluconeogenesis increasing glucose movement out of cells into blood
What does insulin do in muscle and liver
increases glycogen synthesis and inhibits glycogen phosphorylase
what does insulin do in muscle
increase amino acid uptake into muscle
what does insulin do to protein
increase protein synthesis
inhibit proteolysis
What does insulin do in liver
inhibits enzymes of gluconeogenesis
Insulin has what type of effect on growth hormone
Permissive
what does insulin do to K+
promotes k+ ion entry into cells by stimulations Na/K+ ATPASE
Insulin binds to what type of receptor
tyrosine kinase receptor
Insulin half life
5 Mins
Once insulin action is complete what happens to insulin bound receptors
internalised by endocytosis
What 5 factors increase insulin release
Increased BG Increased Amino Acids Glucagon Gastrin/Secretin/CCK/GLP-1, GIP Vagal Nerve Activity
what 4 factors inhibit insulin release
Low BG
Somatostatin (GHIH)
Sympathetic a2 effects
Stress eg Hypoxia
Glucagon is what type of hormone produced by?
Peptide Hormone
Produced by a cells of pancreatic islet cells
What is the primary purpose of Glucagon
Raise Blood Glucose acting mainly on liver
Glucagon half life
5-10 mins
Glucagon is most active
in post absorptive state
Glucagon receptors are what type of receptor
G protein coupled receptors linked to adenylate cyclase/cAMP system which when activated phosphorylate specific liver enzymes
What are the 3 actions of glucagon and what is net result
Increased glycogenolysis
Increased glcuoneogenesis
Formation of Ketones from fatty acids (Lipolysis)
Net result = Elevated BG
What is the formation of ketones from fatty acids called
Lipolysis
Where do the actions of glucagon take place
Liver
Free fatty acids become ketone bodies through
B Oxidation
Brain can only use what for energy
Glucose and Ketones
What do amino acids do in hypoglycaemia
stimulate insulin release which in the absence of glucagon stimulate glucose uptake into cells lowering BG.
Increased glucose does what to insulin and glucagon
Increased insulin
Decreased Glucagon
Decreased glucose does what to insulin and glucagon
Increased Glucagon
Decreased Insulin
Amino acids in plasma stimulate
release of insulin and glucagon
What 5 stimuli promote glucagon release
Low BG <5mm High Amino Acids Symp Innervation and Epinephrine B2 effect Cortisol Stress
What 4 stimuli inhibit glucagon release
- Glucose
- Free Fatty Acids and Ketones
- Insulin
- Somatostatin
Increased Parasymp Activity does what to Insulin and Glucagon
Increases both
Somatostatin is what type of hormone
Peptide hormone
Somatostatin is secreted by?
D Cells of Pancreas
Somatostatin action
Inhibit activity in GI Tract
Entry of glucose into skeletal muscle is increased during exercise when
even in absence of insulin.
Insulin independent increase in GLUT 4 Transporters
Exercise does what to insulin sensitivity of muscle
Increase
In non active muscle insulin binds to
receptor which then leads to glucose transporters GLUT4 migrating to cell membrane allowing glucose to enter
Exercise causes glucose uptake what?
independently of insulin and increases sensitivity of muscle to insulin
When adipose tissue is broken down what is released
Adipose Tissue
In starvation liver will convert excess free fatty acids into
Ketone bodies
Ketone body uptake is
insulin dependent
In poor controlled insulin dependent diabetes what depresses ketone body uptake
lack of insulin
In Type 2 Diabetes what becomes insensitive to insulin
Peripheral Tissues
What happens to B cells in Type 2 Diabetes
Remain intact and appear normal
What percentage of diabetic patients are insulin resistant
90%
Type 1 Diabetes what leads to increase BG
inadequate insulin release
Type 2 Diabetes what leads to increase BG
inadequate tissue response
What is the diagnostic criterion for diabetes
Hyperglycaemia detected by Glucose Tolerance Test
