Diabetes and Obesity Flashcards
What are the nutrition states?
Absorptive State - nutrients supplied by the gut, insulin stimulates glucose use and storage
Post-absorptive state - No nutrients supplied, glucagon maintains glucose levels by mobilising stores and limiting usage
Deep starvation - After 48 hours without food, glycogen reserves are depleted and gluconeogenesis is the only source of glucose (uses muscle mass). The liver converts acetyl-CoA into ketone bodies = ketosis
What is obesity?
Food consumed - energy used = mass gained
When your BMI is > 30 Kg/m2
Obesity is a risk factor for many diseases
They have markers for cancer development
How can obesity be overcome?
Change appetite, activity and thermogenesis (uncouple the electron transport chain)
These changes evolved during scarcity - can be overridden by psychosocial factors
Peptides are involved in mass regulation - leptin and adiponectin
What is leptin?
The product of the obesity gene is leptin
Leptin is a satiety factor
146 residue peptide hormone
Produced by adipocytes (fat cells)
Fat isn’t just storage, it helps regulate homeostasis
What is the mode of action of leptin?
Leptin activates nerves that reduce expression of neuropeptide Y (NPY)
This has the effect of telling the body to eat less
It works with insulin
Ghrelin - balances leptin, it activates other hormones to tell you to eat more
Leptin injections have no weight reducing effects therefore obesity results from additional factors
What is adiponectin?
Adiponectin released by adipocytes when fat stores are full
Acts synergistically with Insulin to promote glucose disposal
The more obese someone is the less adiponectin they produce
It up regulates AMP kinase (AMPK)
In muscles: Increases - fatty acid uptake, beta-oxidation and glucose uptake
In the liver: Increases - Glycolysis and Decreases - Gluconeogenesis and Fatty acid synthesis
How does AMPK regulate fat breakdown?
Acetyl-CoA carboxylase inhibits fatty acid translocation into the mitochondria
Therefore regulates fatty acid synthesis
Activated AMPK phosphorylates ACC and inactivates it
The fatty acids are imported into the mitochondria but synthesis stops after that
What is Diabetes Mellitus?
Produce large quantities of urine containing glucose
High blood glucose levels caused by loss of glucose homeostasis
Symptoms:
Glucosuria, high blood glucose, frequent urination, increased thirst/hunger and dry mouth
What are the types of diabetes?
Type 1 - insulin deficiency
Type 2 - Insulin resistance
Normal levels of glucose are very high - can’t get back to baseline
Gestational - complication of pregnancy
Describe type 1 diabetes?
This is an autoimmune disease
There are few if any beta-cells as the immune system produces antibodies that target beta-cells
If an identical twin has type 1 there is a 30% chance the other will develop it
Treated via insulin injections
Describe type 2 diabetes?
Increased glucose perturbs the normal pathways - leading to insulin resistance
There is a trend that links diabetes and obesity
Lack of Insulin signalling means Glut 4 transporter is not expressed
Therefore excess of glucose extracellularly
Intracellular [glucose] and/or [glucose-6-p] is therefore quite low
Cells respond by metabolising fats and amino acids to replace the missing glucose
Fatty acids metabolised by the liver to produce ketone bodies to replace the lack of glucose
What is ketosis?
Ketone bodies are produced in the liver faster than the can be used in tissues
Ketone bodies are then circulated in the blood (as they are carboxylic acids) they reduce blood pH = acidosis
Spontaneous decarboxylation of acetoacetate yields acetone, which is detectable in the patient’s breath
How is PI3K signalling linked to diabetes?
Defective PI3K signalling = insulin resistance Reduced PI3K signalling is a key mechanism causing insulin resistance in muscle, liver and fat Excess nutrients (Free fatty acids and glucose) can de-sensitise PI3K signalling pathways and prevent the response to further stimulation
What should happen with insulin and what doesn’t with obesity?
Normally - insulin binds to the receptor, becomes phosphorylated and using SH2 domains can interact with other proteins
Obesity - even though insulin binds the pathway doesn’t work
What are some treatments for diabetes?
Diet and activity
Drugs - AMPK agonists and PPAR agonists (increases adiponectin)
The AMPK agonists up regulate AMPK and reduces glucose output from the liver e.g. Metformin
PPAR agonists - Peroxisome proliferator activated receptors
