Lecture 7.1: Endocrine System and Pancreatic Hormones Flashcards
Control System
Controls variables (e.g. blood glucose, body temperature) by maintaining them at an optimal level
Control System:
• Receptor
• Control centre
• Effector
Control System Requirements
• Must be able to monitor the controlled variable
— Receptor (Sensor) e.g. thermoreceptors
• Must be able to compare actual value with what it should be
— Control centre e.g. hypothalamus
• Must be able to change the controlled variable
— Effector e.g. sweat glands
Feedback
Stimulus to Receptor/Sensor
Receptor/Sensor to Control
Control to Effector
Effector to Stimulus
Feedback: Control System
The control system must use the effector to change the controlled variable until the receptor (sensor) indicates it has reached the set point determined by
the control centre
Can change the controlled value by changing the set point
The set point can vary over a 24hr light/dark cycle (circadian rhythm)
Negative Feedback
• Most common
• The effect of the response to stimulus is to decrease its effect
• The effector is switched off when value reaches set point
Positive Feedback
The effect of the response to stimulus is to increase its effect
The effector is not switched off and the control system quickly goes out of control leading to catastrophic change
Examples of positive feedback in the body
• Blood clotting cascade
• Ovulation
• Lactation
What are Hormones?
Hormones are chemical signals produced in endocrine glands that travel in the bloodstream to affect other tissues
Features of Hormones
• Travel to all parts of the body in 30 seconds
• Can have different effects in different places
• The effect that hormone has on target cell depends on its concentration in
the blood stream
• Good for coordinated multiple responses
Hormone Secretion - Endocrine Glands: Head and Neck
• Pituitary gland – anterior and posterior parts
• Thyroid glands
• Parathyroid glands
Hormone Secretion - Endocrine Glands: Abdomen
• Adrenal glands – cortex and medulla
• Pancreas
• Kidney
• Gut
Hormone Secretion - Endocrine Glands: Pelvis
• Gonads (Ovaries, Testes)
• Uterus
• Placenta
Classification of Hormones (4)
• Peptide/Polypeptide hormones (around 20)
• Glycoprotein hormones (4)
• Amino acid derivatives (3 major)
• Steroid hormones (around 10)
What does Hormone Structure define?
• Made
• Transported in the blood
• Interacting with cell receptors
• Inactivated
Peptide/Polypeptide Hormones
Nearly all single chain peptides, varying in chain length
— Thyrotropin-releasing hormone (TRH) - 3 amino acids
— Glucagon- 21 amino acids
— Insulin - 51 aminoacids
— Growth hormone (GH) - 191 amino acids
Some organised in closely related families (e.g. gut hormones)
Glycoprotein Hormones
All have two polypeptide chains with carbohydrate side chains (α and β chains)
— Thyroid stimulating hormone (TSH)
— Follicle stimulating hormone (FSH)
— Luteinizing hormone (LH)
— Human chorionic gonadotrophin (HCG)
Peptide/Polypeptide and Glycoprotein Hormones Similarities
Hydrophilic
Synthesised as larger precursor molecules called pro-hormones (or pre-pro-hormones) and stored in vesicles before release
Cleaved to active hormone and released from vesicles
Amino Acid Derivatives
All of them are derived from tyrosine
Adrenaline
Thyroid hormones:
— Tetra-iodothyronine (thyroxine), T4
— Tri-iodothyronine, T3
Adrenaline
Hydrophilic
Stored in vesicles in adrenal medulla (chromaffin cells)
Thyroid Hormones
Stored extra-cellularly in follicles in thyroid gland as colloid
Hydrophobic
Steroid Hormones
• Derived from cholesterol
• Not stored by cells but synthesised on demand from cholesterol esters
• Hydrophobic
Control of the Hormonal Secretion
The endocrine cells are stimulated chemically (mainly by another hormone) to release hormones
Often related in some way to hormone action
Produces negative feedback control which tends to keep hormone concentration in blood at controlled level
Calcium Homeostasis
Parathyroid hormone (PTH) secretion is stimulated when blood calcium levels fall
PTH acts on bone and kidney to make calcium levels rise which reduces its secretion
Most Common Control of Hormonal Secretion
Many hormones are controlled by other hormones (tropic hormones)
E.g. Secreted by anterior pituitary gland e.g. TSH, ACTH (adrenocorticotropic hormone)
Connection of pituitary gland to brain allows brain to influence the endocrine
system
Hormones Transport in the Blood: Soluble in Simple Solution
Few hormones soluble enough to travel in simple solution such as:
• Peptide/Polypeptide and glycoprotein hormones
• Adrenaline (amino acid derivative hormone)
Hormones Transport in the Blood: Must bind to proteins
• Often specific
• Steroids
• Thyroid hormones (amino acid derivative hormone)
Inactivation of Hormones
Inactivation may occur in target tissues, but also in other tissues, especially in the liver
Peptides/Polypeptides are degraded to amino acids
Steroids and amino-acid derivatives have small changes in structure or are recycled/excreted
Pancreas
An organ of digestive and endocrine systems
Anatomically divided into: head, body and tail
Histologically/Functionally divided into: Endocrine (2%, e.g.insulin, glucagon) and Exocrine (98%, e.g.digestive enzymes)
Functions of Pancreas: Exocrine
Produces digestive enzymes (amylases, lipases, proteases etc.)
Alkaline secretions drain into pancreatic duct, then into duodenum
Functions of Pancreas: Endocrine
Produces polypeptide hormones:
• Insulin and glucagon- regulate blood glucose
• Somatostatin- inhibits islet secretions
• Pancreatic polypeptide, ghrelin and amylinregulate appetite
Insulin and Glucagon Control Glucose
α-cells:
• Blood glucose needs to be tightly controlled
• Insulin lowers blood glucose levels
• Glucagon raises blood glucose levels
β-cells:
Insulin sensitive: adipose, skeletal muscle, liver
Insulin: Actions and Metabolic Effects
• Stimulated by feeding
• Affects metabolism of carbohydrates, lipids and proteins
• Increases protein synthesis
• Promotes energy storage (anabolic), reducing blood glucose
Insulin: Target Tissues
• Skeletal muscle
• Liver
• Adipose tissue
• Glycogenic (liver, muscle)
• Anti-gluconeogenic (liver)
• Anti-lipolytic (adipose tissue) and anti-ketogenic (liver)
Glucagon Actions and Metabolic Effects
• Stimulated by fasting
• Affects metabolism of carbohydrates and lipids
• Mobilises energy stores (catabolic), increasing blood glucose
Glucagon: Target Tissues
• Liver
• Adipose tissue
• Glycogenolytic (liver)
• Gluconeogenic (liver)
• Lipolytic (adipose tissue) and ketogenic (liver)
What is between Preproinsulin and Insulin?
Preproinsulin to Proinsulin to Insulin
Mature Form of Insulin
Insulin consists of two polypeptide chains connected by two disulphide bridges between cysteines
The third disulphide bond is in chain A
3 disulphide bridges: rigid structure
Insulin Secretion
Mature secretory vesicles move along microtubules towards the plasma
membrane of β-cell (margination)
Upon stimulation of β-cell by glucose, calcium enters the cell:
• Vesicle membranes fuse with plasma membrane
• Calcium induces contraction of microfilaments leading to release of insulin
and peptide C from vesicles by exocytosis
Glucose Stimulated Insulin Secretion
• Glucose transported into β-cell by facilitated diffusion (GLUT2)
• Glucose is utilised providing ATP which closes K+ channels
• Increased intracellular K+ levels lead to membrane depolarisation
• Influx of extracellular Ca2+
• ↑ Intracellular Ca2+ triggers release of insulin from secretory vesicles
What can be used to treat Type 2 Diabetes?
Insulin secretagogues such as sulphonylureas (SUR) are used to treat Type 2 Diabetes
How does Insulin Exert its Action through Insulin Receptors?
Insulin receptor (tyrosine kinase receptor) on target cell
Transmembrane dimer:
• Two identical monomers
• Each monomer has one α- and one β-subunit, connected by single disulphide
bonds
α-subunit and β-subunit of Insulin Receptor
α-subunit is extracellular and insulin binding
β-subunit is intracellular (Spans the plasma membrane has activity of tyrosine kinase)
Activation of the Insulin Receptor
Following insulin binding to receptor on target cell:
• α-subunits move towards each other, wrap the insulin
• β-subunits move towards each other & pull insulin into cell (internalisation)
• β-subunits become an active tyrosine kinase
• Tyrosine residues undergo autophosphorylation
• Active tyrosine kinase phosphorylates tyrosine residues in other protein
• Activation of signalling pathways and metabolic effects
How is Glucose uptake via Insulin regulated?
1) Insulin binds to receptor
2) Signal cascade
3) This causes exocytosis of GLUT4
4) This permits glucose entry
Glucagon Synthesis in a-cells
• Synthesised as large precursor: pre-proglucagon
• Cleaved to glucagon- a single polypeptide chain (29 a.a.)
• No di-sulfide bridges: flexible structure
Synthesised in and excreted from a-cells:
• Synthesised in RER, transported to Golgi and packaged in secretory
granules
• Secretory granules move to cell surface by margination and release
contents into blood by exocytosis
Glucagon Exerts its Action through Glucagon Receptor
• Glucagon binds to G-protein coupled receptor (GPCR)
• α-subunit activates adenylate cyclase which leads to production of cAMP
• cAMP activates PKA leading to signalling cascade and metabolic effects
Clinical Signs of Abnormal Insulin Levels
• High levels result in hypoglycaemia
• Low levels result in hyperglycaemia (diabetes mellitus)
• Insulin resistance results in hyperglycaemia and hyperinsulinaemia
Clinical Signs of Abnormal Glucagon Levels
• High levels worsen diabetes
• Low levels may contribute to hypoglycaemia
