Glucose Metabolism Flashcards
How is glucose manufactured?
Gluconeogenesis and glycogenolysis
Which organ does not need insulin for glucose uptake?
Brain
How can injection of somatostatin treat hypoglycaemia?
- Somatostatin receptors coupled to voltage gated Ca channels in pancreatic B cells
- Somatostatin blocks channel
- Reduces Ca influx and inhibits insulin secretion
Which receptors facilitate non-insulin mediated glucose transport?
GLUT 1 and GLUT 3
Which receptors mediate glucose uptake in fat and muscle?
GLUT 4
What is the mechanism of GLP1 analogues in treating diabetes?
- GLP1 is an incretin
- Stimulates insulin production
What might be the consequence of glucokinase mutation?
- Inheritable diabetes
- Glucose not broken down to ATP as easily
Which chain of insulin is most active at the receptor?
A chain
Insulin is synthesised exclusively in the ____ cells of the _____
Beta cells of pancreas
Describe the synthesis and release of insulin.
- Glucose transported into beta cell by facilitated diffusion via glucose transporter -> inc. [glucose] in beta cell
- Glucose -> glycolysis -> ATP -> closure of K+ sensitive channels -> depolarisation
- Influx of Ca -> insulin translocation and exocytosis
Why do patients often gain weight after starting on insulin?
- Stimulates triglyceride storage
- Inhibit lipolysis and FFA production
- Inhibit ketone production
What is the influence of insulin on carbohydrates?
- Lier
- Muscle
- Adipose
- Liver: inhibit gluconeogenesis and glycogenolysis
- Muscle: increase glucose transport and glycolysis
- Adipose: same as muscle
What is the influence of insulin on protein?
- Anabolic
- Increase transport of AA to liver and muscle
What are incretins?
Hormones secreted into blood minutes after eating that inc. production of insulin
What is the mechanism of sulfonylureas?
- Close ATP sensitive K channels in beta cell plasma membrane
- Initiate cascade resulting in insulin release
What do we measure clinically in patients with severe recurrent hypoglycaemia?
C peptide
High insulin and low C peptide
In the Kreb cycle ____ is oxidised for energy
Acetyl CoA
How are free fatty acids metabolised?
- Cannot enter Kreb cycle
- Mostly metabolised in liver and muscle to ketone bodies
What are three ketones produced in the body?
- Acetoacetate
- Acetone
- Beta hydroxybutyrate
Which ketone can be measured clinically?
- Beta hydroxybutyrate
What is the pathophysiology of diabetic ketoacidosis?
- Lack of insulin, so no glucose in cells (no energy source)
- Glucose accumulates in blood stream
- Activation of hormone sensitive lipase -> lipolysis
- Also breakdown of glycogen
What are the clinical findings of a patient with diabetic ketoacidosis?
- Very high blood sugar
- Severe acidosis
- Hypotensive
- Volume depleted
What is the range of normal fasting glucose?
3.5-5.5 mmol/L
What happens when diabetics become hypoglycemic?
- ANS activated ~3.0mmol/L
- NA release - sweating, tremor, increased HR, dilated pupils etc.
Which hormones are most important in the counter regulation of hypoglycaemia?
- Adrenaline and glucagon
Also cortisol.
What are four causes of hypoglycaemia?
- Insulin in diabetic patients
- Sulphnylurea therapy
- Insulinoma
- Severe hormone deficiency e.g. Addison’s disease