Diabetes Mellitus Flashcards
What is the boundary for hypoglycaemia
<4-5MM
What can hypoglycaemia cause
Impaired brain function
What can happen when glucose level is under 3mM
unconsciousness, coma , death
Which hormones control glucose regulation
Insulin Glucagon Cortisol Catecholamines Somatrophin
What is type 1 DM
Elevated glucose levels where insulin is required to prevent ketoacidosis
What is type 2 DM
More common. Defined in terms of glucose but is also related to hypertension and dyslipidaemia
When does hypoglycaemia occur
Imbalance between diet, exercise and insulin
What does treatment aim to help
Symptoms, complications (morbidity) and mortality
What is common in DM treatment
Diet, insulin and capillary glucose monitoring
How much of the pancreas do langerhans take up and what does the rest of the pancreas do
2%
Involved in exocrine secretions via pump
What cell junctions can you find between langerhans cells
Gap junctions to allow small molecules to pass and tight junctions to form small intercellular spaces
What are the types of langerhans cell
alpha - glucagon
beta - insulin
delta - somatostatin
What are the principal actions of insulin
Increased glycogensis
Increased glycolysis
Increased glucose transport into cells via GLUT4
Decreased lipolysis
Increased lipogenesis
Increased amino acid transport and increased protein synthesis
What are the principal actions of glucagon
Increased hepatic glycogenolysis Increased blood glucose Increased amino acid transport to the liver Increased gluconeogenesis Increased lipolysis Increased gluconeogenesis
Which factors regulate the release of insulin
Increasing blood glucose
Certain amino acids
Certain gastro intestinal hormones (GLP)
Sympathetic control (-) and parasympathetic (+)
What factors regulate the release of glucagon
Decreasing blood glucose
Certain amino acids
Certain gastro intestinal hormones
Sympathetic (++) and parasympathetic (+) control
Describe the beta-cell sensing mechanism of glucose
Glucose -> G-6-P -> Metabolic pathways -> insulin synthesis and release.
Glucokinase/ hexokinase IV is the “glucose sensor” as it is in the rate limiting step
Describe the process of insulin secretion
- glucose enters via GLT 2
- conversion to G-6-P by glucokinase
- ATP blocks the ATP sensitive K+ channel
- Voltage dependent Ca+ channel opens
- Insulin secreted
Describe the insulin receptor
Mostly on muscle, can be on liver
not responsible for type II DM
Made of alpha and beta subunits
What does the alpha subunit of the insulin receptor do
Recognises the 3D insulin structure
What does the beta subunit of the insulin receptor do
Has tyrosine kinase domains where phosphorylation occurs
What is GLP-1
Glucagon-like peptide 1
What does the GLP-1 do
Gut hormone that is secreted in response to nutrients in the gut. Stimulates insulin secretion and glucagon suppression. Increases satiety.
What is the half life of GLP-1
Short half life due to rapid degeneration from enzyme dipeptidyl peptidase-4 (DPPG-4)
How is GLP-1 produced
Transcription product of proglucagon gene, mostly from the langerhans cells
What is the effect of insulin on glucose
Decreased hepatic glucose output and increased muscle intake
What is the effect of insulin on protein
Decreased proteolysis
What is the effect of insulin on lipids
Decreased lipolysis and decreased ketogenesis
What is GLUT-4
A receptor that allows glucose uptake through the membrane. They lie in vesicles and become incorporated into the membrane by insulin resulting in a 7 fold increase in uptake
What does cortisol stimulate
Proteolysis
Which hormones stimulate protein synthesis
Insulin and IGF I
What is the main short term energy store
Glycogen
After short-term fasting what is used to maintain glucose levels
gluconeogenesis using proteins
Describe the formation of glycerol and NEFA from TAG
- Triglyceride is broken down by lipoprotein lipase, promoted by insulin
- Glucose enters through GLUT-4, stimulated by insulin
- Glucose can be broken down and two components can be used to form triglyceride, these being glycerol-3-p and NEFA, again promoted by insulin
- This can be used to stop the break down of triglyceride into glycerol and NEFA
Describe the circulation glycerol
- Glycerol reaches the liver
- It enters the cell and is phosphorylation
- Formation o triacyl glycerol
- This can be used to synthesise glucose (hepatic glucose output)
What is the importance of the way glycerol circulates
Blood flows through the gut before the liver, allowing for food to be processed before entering the liver. Adipocytes in the central circulation of different those in the limbs
What can eat brain utilise as an energy source
Glucose and ketone bodies (NOT fatty acids)
What is fat used for in metabolism
Broken down and used in Krebs> Non-esterified fat cannot be used to synthesise glucose
How are ketone bodies formed
- Fatty acids enter the liver
- Fatty acids are broken down into segments
- Formation of ketone bodies (acetoacetate and 3-hydroxybutarate)
Which molecule can be used as an indication of insulin
Ketone bodies as insulin inhibits their formation
What occurs during fasting
Low insulin to glucose ratio Increasing non-esterified fatty acids Increase in proteolysis and lipolysis Break down of glycogen Gluconeogenesis
What occurs during prolonged fasting
Decrease in amino acids
Increased ketogenesis
Brian uses ketone
Which molecules do the muscle and brain use
Muscle = lipids Brain = glucose
What occurs when one is fed
Stored insulin is released then a second phase insulin release
High insulin to glucagon ratio
Hepatic glucose output is stopped
Increase in glycogen formation
Decreases in gluconeogensis and proteolysis
Increase in protein synthesis and lipogenesis
What are the signs and symptoms of type 1 DM
Weight loss Hyperglycaemia Glycosuria with osmotic symptoms Ketonuria Given an intramuscular injection of insulin
What causes weight loss in T1 DM
Proteolysis and lipolysis
What is the difference between T1 and T2 DM
T1 = absolute insulin deficiency T2 = insulin resistance
Where does insulin resistance reside
Adipose, muscle and liver
Why don’t T2 DM patients lose weight
There is enough insulin to suppress proteolysis and lipolysis
What are the two pathways that occur when insulin meets its receptor
MPAK or PI3K-Akt
How does insulin resistance affects the pathways
PI3-Akt is inhibited so the MAPK pathway is enhanced
What are the two pathways responsible for
MAPK = growth, proliferation, growth in utero, blood pressure and dyslipidaemia PI3-Akt = metabolic actions (glucose, fat and amino acids)
What are the effects of hyperinsulinaemia via the MPAK pathway
Excess stimulation of the mitogenic pathway
Low LDL cholesterol and high HDL
Smooth muscle hypertrophy -> high blood pressure
Ovarian function (polycystic ovary syndrome)
Clotting
Energy expenditure
What are the effects of the insulin resistance via IP3-Akt
Glucose, protein and lipid metabolism affected
What happens to lipoproteins in humans with T2 DM
Predominantly abnormal lipoproteins that is lipid carriage in the circulation, contributing to damage to the artery
What is insulin resistance associated with
Hyperglycaemia
Greater waist circumference
High blood pressure
High triglyceride and low LDL
What can patients with T2 DM present with
Obesity (60-80%) Dyslipidaemia Hyperglycaemia Insulin resistance and later deficiency Complications due to central adiposity Less osmotic symptoms
Describe the features of a diet for patients with DM
Total calorie control Reduce calories as fat and as refined carbohydrate Increase calories as complex carb Increase soluble fibre Decrease sodium intake
