The Endocrine Pancreas Flashcards
Anatomy of the pancreas
Found posterior to the stomach and liver but anterior to the kidneys
Found superior to the SI but inferior to the liver and kidneys
Receives arteries from the celiac trunk and secretes enzymes into the duodenum and hormones into the blood stream
Pancreas is essentially a large gland and develops embryologically as an outgrowth of the fore growth
Functions of the pancreas
Pancreas has two functions
– produces digestive enzymes secreted directly into duodenum (exocrine action)
Exocrine function forms the bulk of the gland
Alkaline secretions via pancreatic duct to duodenum
hormone production (endocrine action) From Islets of Langerhans ~ 1% endocrine tissue, 99% exocrine tissue
Endocrine pancreas function
Important polypeptide Hormones secreted by pancreas:
Insulin found in Beta cells
Glucagon found in Alpha cells
Somatostain found in Delta cells
Pancreatic Polypeptide (PP) found in PP cells
Ghrelin found in E cells
Gastrin found in G cells
Vasoactive intestinal peptide (VIP) found in VIP cells
Hormones for glucose regulation
Why is plasma glucose concentration important
Theses hormones are insulin and glucagon - Both water soluble hormones
Carried dissolved in the plasma - no special proteins
Short half life - 5 min
Interact with cell surface receptors on target cells
Receptor with hormone bound can be internalised - inactivation
Actions of insulin and glucagon - both involved in the regulation of metabolism of carbohydrates, protiens and fats
Insulin lowers blood glucose levels - released when fed - targets liver, adipose and skeletal muscle - anabolic as binds glucose from the blood into storage in tissues
Glucagon raises blood glucose levels - released during fasting - targets liver and adipose - catabolic as it breaks down stored glucose in cells and releases it into the blood
Why important - Brain uses glucose at fastest rate in body
– Relies on blood
Sensitive to falls in glucose
or rise = increased osmolarity
Circulation glucose needs to be controlled
Normally 3.3-6 mmol/L (UHL reference range)
After a meal 7-8 mmol/L
Renal threshold 10 mmol/L
– Glycosuria (can see insulin in urine)
in pregnancy, renal threshold decreases (not pathologic as renal threshold goes down in pregnancy for people)
in the elderly, renal threshold increases
Insulin
Action (favours storage) it is the hormone of energy storage
Remember to construct glucose from smaller units is called - gluconeogenesis
Insulin is anti-gluconeogenic - at high dosage lowers incorporation of pyruvate-into blood glucose, but also stimulated its incorporation into liver glycogen
Insulin is Anabolic
anti-gluconeogenic
anti-lipolytic and anti-ketogenic
Synthesis and secretion-
KATP channels - regulated by metabolism
Resting membrane potential of excitable cells depends of K+ ions distribution
Efflux of K+ causes hyperpolarsatiion of RMP
Influx of potassium ions leads to depolarisation
In ß cells when no glucose is present KATP channels are open and allowing K+ to exit the cell - membrane is hyperpolarised and Ca2+ channels stay closed
When glucose is present - metabolism in the cell occurs producing more ATP, which subsequently closes KATP channels, therefore K+ remains in the cell causing the membrane to depolarise and calcium channels open, allowing calcium to flow in causing Insulin to be released
Plasma membrane KATP channels provide a link between membrane excitability and metabolism
Glucose closes Katp channels in pancreatic beta cells
Metabolic inhbiiton reopens of Katp channels
KATP channels - insulin secretions
Membrane topology of Kir6.2 channel and sulfonylurea receptor subunits
When metabolism is low the KATP channels are open and no insulin is secreted
When metabolism is high (i.e. glucose is present), KATP channels shut and insulin is secreted
Metabolic effects of insulin
Insulin…. What does it do?
Increases glucose uptake into target cells and glycogen synthesis (insertion of Glut 4 channel )
In the liver it increases glycogen synthesis by stimulating glycogen formation and by inhibiting breakdown
In muscles it increase uptake of AA promoting protein synthesis In liver inhibits breakdown of AA In adipose tissue increases the storage of triglycerides inhibits breakdown of fatty acids
Insulin receptor
Insulin binds to the insulin receptor on cell surfaces
receptor is a dimer
two identical subunits spanning the cell membrane.
two subunits are made of one alpha chain and one ß chain, connected together by a single di-sulphide bond
alpha chain on exterior of cell membrane
ß chain spans the cell membrane in a single segment
Glucagon
Hormone that opposes insulin – acts to raise blood glucose levels – It is glycogenolytic, – gluconeogenic – lipolytic – ketogenic it mobilizes energy release
Synthesis and secretion-
Disorders of blood glucose
Diabetes mellitus - mellitus (L) = honeysweet
Group of metabolic diseases - Affect >2% of population in UK
Characterised by
– chronic hyperglycaemia
– leading to long-term clinical complications
Associated with elevated glucose levels in urine (can tell if its DM or diabetes insipidus due to the sweet tasting urine)
Diagnosis of DM - Diagnosis basis of venous plasma glucose concentration:
normal range 3.3-6mmol/L plasma glucose (UHL reference range)
fasting
Type1 or Type 2 DM
Diabetes mellitus is caused by:
Type 1 – absolute insulin deficiency
(Autoimmune destruction of Pancreatic
Insulin resistance
Main sites of glucose utilisation (adipose, liver & skeletal muscle) show decreased response to normal circulating concentrations of insulin.
Affects: ~ 25% of general population ~ 92% of patients with type 2 diabetes Results from combination of: genetic factors environmental factors including: obesity sedentary lifestyle
Insulin resistance: In the young
Insulin resistance present before ( 12+ years) onset of hyperglycaemia & development of overt type 2 diabetes.
Initially: ß-cells compensate by increasing insulin production - maintains normal blood glucose.
Eventually: ß-cells unable to maintain increased insulin production - impaired glucose tolerance. Finally: ß
