Intro To Doabetes Flashcards
GLUT 4
Found in myocytes and adipocytes
Respond to insulin
Recruited and enhanced by insulin
How does insulin affect proteolysis and protein synthesis respectively in myocytes in the fed state?
Inhibits proteolysis as protein is not needed as a fuel source
Stimulates protein synthesis to use the proteins for storage
What effect does GH and IGF-1 have on protein synthesis in myocytes
Stimulates it as it converts amino acids into protein for storage
- What effect does cortisol have on proteolysis in myoctes?
Stimulates it
What hormone leads to an increase in uptake of gluconeogenic amino acids in the liver?
Glucagon
What is the effect of glucagon on the liver in the fasting state?
- Gluconeogenic amino acids released from myocytes enter liver which glucagon helps
- Glucagon stimulates proteolysis to produce more gluconeogenic amino acids
- Glucagon increases gluconeogenesis (to form glucose) to increase hepatic glucose output (HGO) → cortisol also does this
What is the effect of insulin on the liver in the fed state?
- Insulin inhibits gluconeogenesis in liver to reduce hepatic glucose output
- Stimulates protein synthesis
How long do carb, protein and fat stores in the body last?
- Carb- 16 hours → are depletable within a 1 day fast
- Protein- 15 days
- Fat- 30 to 40 days
What does Lipoprotein Lipase break Triglycerides (in the blood stream) down into and what hormone is this process stimulated by?
Glycerol and non esteriged fatty acids
Stimulated by insulin
How does insulin interact with adipocytes in a fed state? (2 things)
Increases uptake of glucose via GLUT-4
Converts Glycerol and NEFA into triglycerides again for later use when needed - lipogenesis
- Insulin also inhibits breakdown of triglycerides in adipocytes as you don’t need alternative energy source
What happens to adipocytes in fasting state (recall the two hormones involved)?
- Blood glucose and insulin is low so GH and cortisol secretedThese stimulate breakdown of triglycerides into Glycerol and NEFA to be used as an alternative energy source once transported into the liver - stimulates lipolysis
In the fasting state what happens to the glycerol taken up by the liver?
It is converted into glucose in process, gluconeogenesis
Increasing hepatic glucose output
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In the fed state what happens to the glycerol taken up by the liver
Converted into triglycerides
What fuel can the brain use?
- Glucose- preferred energy source
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Ketone bodies
Can’t use NEFA as a fuel
- How are ketone bodies produced?
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- NEFA released from adipocytes are taken up by liver
- In fasting state, glucagon is released which promotes conversion of NEFA into ketone bodies to be used as alternative energy source
In the fed state, what does insulin do once NEFA is uptaken by the liver?
NEFA converted into fatty Acyl-CoA
Insulin inhibits the conversion of Fatty Acyl-CoA into ketone bodies
This prevents it from being used as an alternative metabolic substrate to glucose
The opposite happens in the fasting state where ketone bodies are produced
In the fed state what happens to glucose in the liver?
It is converted into Glucose-6-P
This is then converted into Glycogen (stimulated by insulin)
In the fasting state what happens to glycogen in the liver?
is broken down into glucose-6-p which gets turned into glucose and outputted from liver (process stimulated by glucagon) - Glycogenolysis
What does it mean if there is a high level of ketones and glucose?
There is an issue with insulin secretion
In the fed state what happens to Glucose in myocytes?
It is converted into glycogen to be stored and used only when the myocyte needs energy
It is also used in aerobic respiration
What effect does Glucagon and GH have on the GLUT-4 transporters in myocytes?
Inhibits uptake of glucose via GLUT-4 to allow more glucose to remain in circulation and increase the blood glucose levels
In the fasting state why is amino acid concentration increased initially and then decreased when prolonged?
Increased due to increased proteolysis and then decreased due to more gluconeogenesis to increase hepatic glucose output
What is the spike in insulin when you eat referred to as?
First Phase Insulin Release
What overall happens in body in fasted state?
- Low insulin-to-glucagon ratio
- (normal glucose is maintained at 3-5.5 mmol/L)
- Increased NEFA from increased lipolysis
- Increased proteolysis so increased amino acids but they decrease when prolonged fast
- Increase in HGO from glycogen and gluconeogenesis
- Muscles use lipids and brain uses glucose and later ketones
- Increased ketogenesis when prolonged
What overall happens in body in fed state?
- Stored insulin released in 1st phase then slow release in 2nd phase
- High insulin-to-glucagon ratio
- Stop HGO
- Increased glycogen storage, lipogenesis and protein synthesis
- Decrease gluconeogenesis and proteolysis
Describe the pathophysiology of Type 1 Diabetes Mellitus (T1DM)
Autoimmune condition that eventually leads to a T-Cell mediated destruction of the insulin-producing beta cells in the pancreas, leading to absolute insulin deficiency
- Leads to protein lysis into AAs, increased HGO
How does T1DM lead to osmotic diuresis?
Increased glucose in blood (hyperglycemia) so more glucose in urine
Lowering water potential of the urine, so water enters urine via osmosis, leading to a lot of water loss
How does diabetic ketoacidosis occur? (explain the mechanism, involving one of the pancreatic hormones)
Less insulin is there to down-regulate the breakdown of triglycerides in adipocytes
So more triglycerides are broken down into NEFA and Glycerol
NEFA are then converted into ketone bodies in the liver (which would also normally be inhibited by insulin), leading to a build up of ketones
What do patients with T1DM usually present with?
- Weight loss
- Hyperglycaemia
-
Glycosuria (glucose in urine) with osmotic symptoms:
- Polyurialots of urine made
- Polydipsiafeeling very thirsty due to losing so much fluids
- Nocturiapassing of urine in night
- Ketones in blood and urine
- What (4) useful diagnostic tests help distinguish between t1 and t2?
- Antibodies: GAD, IA2
- Low c-peptide
- Presence of ketone bodies
- GAD (glutamic acid decarboxylase), IA2 (islet antigen 2)
Which (4) hormones induce a counterregulatory response to hypoglycemias
Glucagon
Catecholamines
Cortisol
Growth Hormone
- What is the counterregulatory response to hypoglycaemia?
Increased HGO with glycogenolysis and gluconeogenesis
Increased lipolysis
Why is it important to avoid hypoglycaemia?
- Makes people feel awful and lethargic
- Recurrent episodes of hypoglycaemia can lead to impaired awareness of hypoglycaemia where our body gets used to being hypoglycaemic so we have a reduced ability to recognise symptoms until glucose is much lowe
Signs of hypoglycemia
Shaking
Sweating
Pallor
Palpitations
Seizures
Slurred speech
Poor vision
Confusion
Loss of consciousness
What is the management for t1dm like?
- Exogenous insulin (basal-bolus regime) → multiple daily injections (long acting injection once a day and short acting ones before you eat)
- Self-monitoring of glucose e.g. finger prick test
- Structured education
- Technology like insulin pumps and continuous glucose monitoring tech
- Monitoring and prevention of long term diabetes complications like retinopathy, neuropathy, nephropathy etc
Type 2 diabetes
Insulin resistance in liver muscle and adipose tissue however there is enough insulin to suppress ketogenesis and proteolysis
What tests can be carried out to make a diagnosis of Type 2 diabetes?
Fasting glucose > 7.0mmol/L
Random glucose > 11.1mmol/L
Oral glucose tolerance test
HbA1c (>48mmol/L) (haemoglobin becomes glycated due to persistent hyperglycaemia in T2DM)
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Red two positive test or one positive test and symptoms
How do T2DM patients present?
Insidious onset
Dyslipidaemia
Hyperglycaemia
Overweight
Less osmotic symptoms than t1
Insulin resistance
Later insulin deficiency
- What effect does insulin resistance have on Triglyceride and HDL concentration?
High Triglyceride concentration in plasma as insulin function is lacking and so LPL cannot breakdown TG into Glycerol and NEFA
Low HDL concentration - overproduction of VLDL leading to increased TG plasma levels which results in lower levels of HDL
Type 2 diabetes treatment
- Total calories control
- Reduce calories as fat and refined carbs
- Increase calories as complex carb and soluble fibre
- Decrease sodium
- Oral medication
- Structured education
- May need insulin later if beta cells stop working
- Monitoring and prevention of long term complications
What are some of the long-term diabetes complications that can be avoided through certain management strategies
Retinopathy (microvascular)
Neuropathy (microvascular)
Nephropathy (microvascular)
Cardiovascular (macrovascular)
