The Endocrine Pancreas - Part 2 Flashcards
What happens if there is more glucagon than insulin?
Glucose released into plasma from stores and BG conc. increases
Increased glycogenesis, gluconeogenesis and ketogenesis
Describe glucagon
Peptide hormone produced by alpha cells of pancreatic islet cells
Glucose mobilizing hormone, acting mainly on the liver
What is the plasma half life of glucagon?
5-10 mins
Degraded mainly by the liver
When is glucagon most active?
In post absorptive state
What are glucagon receptors?
G protein coupled receptors
Linked to adenylate cyclase/cAMP system which when activated phosphorylate specific liver enzymes
What is the action of glucagon?
Opposes the action of insulin, part of the glucose counter regulatory control system which included epinephrine, cortisol and GH
What does phosphorylation of specific liver enzymes result in?
Increased glycogenolysis
Increased gluconeogenesis
Formation of ketones from FAs
What is glycogenolysis?
Breakdown of glycogen to return to glucose
How does fasted state metabolism maintain plasma glucose for brain?
Liver glycogen becomes glucose
Adipose lipids become free FAs and glycerol that enter blood
Muscle glycogen is used for energy -use FAs and break down proteins into aa
Brain can only use glucose and ketones
How are ketone bodies formed?
Beta oxidation from free fatty acids
What do amino acids stimulate and why is it important?
Stimulate glucagon and insulin
If no glucagon stimulation then glucose uptake into cells and lowered BG conc.
Potentially catastrophic for brain - hypoglycaemia
Adaption was for high protein meals
What happens if someone consumes a very high protein meal?
Amino acids stimulate insulin causing decreased BG conc.
Also stimulates glucagon causing increased BG conc.
This maintains BG conc.
Explain glucose sparing for obligatory glucose users
In post absorptive state then there is low insulin levels so a large mass of tissue like muscle and fat can not readily access glucose
What are some stimuli which promote glucagon release?
Low BG conc. (under 5 mM)
High conc. of amino acids
Sympathetic innervation and epinephrine, Beta 2 effects
Cortisol
Stress
What stimuli inhibit glucagon release?
Glucose
Free fatty acids and ketones
Insulin
Somatostatin
What happens if increased parasympathetic innervation on islets cells?
Increased insulin and lesser increase of glucagon
Association with anticipatory phase of digestion
What happens if increased sympathetic innervation on islets cells?
Promotes glucose mobilization
So increased glucagon, epinephrine and inhibition of insulin so brain had enough energy
How does epinephrine help control BG conc.?
Muscle and liver glycogenolysis
Gluconeogenesis
Lipolysis
How does cortisol and GH help control BG conc.?
Gluconeogenesis
Inhibition of glucose uptake
Lipolysis
Cortisol only - protein catabolism
What is somatostatin?
SS is a peptide hormone secreted by D cell of the pancreas
Main pancreatic function is to inhibit activity of GI tract
What is another action of somatostatin?
Supresses the release of both insulin and glucagon
If SS tumour then can have symptoms of diabetes
Describe the effect of exercise on conc. of BG?
Entry of glucose into skeletal muscle increases even in absence of insulin
There is insulin independent increase in GLUT4 in muscle membrane
Also increases insulin sensitivity of muscle
Explain GLUT4 transporters in active muscle
Can migrate to membrane without insulin being present
Exercise causes glucose uptake independent of insulin
Describe what happens during starvation
Adipose tissue is broken down - fatty acids are released
Most tissues can used FFAs to make energy and liver converts excess to ketones - additional source of energy
What happens to the brain after a period of starvation?
Brain adapts to be able to use ketones
Why does the brain adapt to use ketones as energy source?
Serves to save protein breakdown as can become weak and vulnerable to infection
Ketone body uptake is insulin dependant
Describe Type I diabetes (IDDM)
Inulin dependant diabetes mellitus
Autoimmune destruction of the pancreatic beta cells destroys ability to produce insulin and compromises ability to absorb glucose
What are the results of type I diabetes?
Absolute need for insulin - insulin injections
Without then develop ketoacidosis, coma and die
Describe the breakdown of homeostatic regulation in diabetes
Meal increases BG conc. but lack of insulin effect so liver produces more glucose by gluconeogenesis because body thinks its starving - further increase in BG conc.
Describe ketoacidosis in type I diabetes
Lack of insulin depresses ketone body uptake so build up rapidly in plasma - acidic so create life threatening acidosis with plasma less than 7.1
How are ketones detectable?
Detectable in urine and produce distinctive acetone smell to breath
Describe type II diabetes
Non-insulin dependant diabetes mellitus
Peripheral tissues become insensitive to insulin - insulin resistance
Either abnormal insulin response of receptors or reduction in number of receptors
What are the beta cells like in type II diabetes?
Intact and appear normal
Can sometimes even be hyperinsulinemia
What are major contributions to type II diabetes?
High sugar and animal fat diet with little exercise
Describe the glucose tolerance test in diabetes
Type I and type II give raised BG conc.
Type I - inadequate release of insulin
Type II - inadequate tissue response
Patient ingests glucose after fasting BG measures then if elevation after 2 hrs - indictive of diabetes
How is mg/dl converted to mM?
Ex. 90mg/dl x 100 to make L
900mg/l
MW of glucose is 180
900/180 - 5mM
What are some diabetic complications of long term hyperglycaemia?
Retinopathy
Neuropathy
Nephropathy
CVD
What can hypoglycaemia in type I diabetes cause?
Type I on exogeneous insulin
Can lead to permanent brain damage and death in end
Only needs to be over short period to see complications
