Week 3. Glucose and Insulin Flashcards
What is the difference between type 1 and type 2 diabetes?
Type 1 is the inability to produce insulin.
Type 2 is a resistance to insulin.
What is gluconeogenesis and how does it occur?
Gluconeogenesis is the production of glucose from non carbohydrate sources.
- fatty acids can’t be used to produce glucose. Glycerol can.
Glycerol –> triose P –> glucose
Erythrocytes –> lactic acid –> pyruvate –> triose P –> glucose
Muscles:
amino acids –> pyruvate –> triose P –> glucose
- life threatening
How does a beta cell release insulin?
- Glucose is used to generate ATP.
- As ATP is produced, the potassium channels close and the membrane is depolarised.
- This opens the voltage gated calcium channels. Calcium floods into cell and intracellular calcium stores are released.
- The increasing calcium conc causes the insulin granules to exocytose
- Insulin released into circulation.
What does the body use if glucose isn’t available?
Fat reserves. The body can maintain glucose levels at 3mM for four weeks using fat reserves with no adverse effects.
How does the body increase glucose levels in the fasted state?
- muscles use fatty acids, which inhibits the uptake of glucose
- liver converts glycogen to glucose
What are some of the micro and macro vascular complications of diabetes?
Macrovascular: atherosclerosis/CHD/stroke
Microvascular: nephropathy, retinopathy, neuropathy
Outline the structure and function of the pancreas?
- endocrine and exocrine functions
- 1 million endocrine cells in islet of langerhans
- Islet only makes up 1-1.5% of pancreas weight: 1-2g in adults
- 5 types of islet cell
- endocrine pancreas receives 5-10 times more blood than exocrine pancreas
- highly innervated –> sympathetic, parasympathetic and sensory neurones
What does insulin do to muscle?
- inhibits protein degradation
- stimulates amino acid uptake
- stimulates protein/glycogen synthesis
Where is insulin synthesised?
In the beta cells, which make up 55% of islet volume.
How much insulin does a healthy pancreas release per day?
1mg
What is insulin initially synthesised as?
Pre-proinsulin
How is glucose uptake by cells regulated?
- glucose uptake in liver is not regulated by insulin, only by glucose concentration in ECF
- -> same for kidneys, intestines, and beta cells
- liver has a very high affinity for glucose and can’t be saturated
- the brain has a constant uptake of glucose
- Insulin controls glucose uptake in adipose tissue and muscles
What is the significance of c pepide?
- released with insulin in a 1:1 ratio
- degraded in kidney
- half life 3/4 longer than insulin
- marker of normal insulin production
- -> can be used to distinguish between type1 and type2 diabetes
How much glucose does the brain use per day?
120g
What does insulin do to the liver?
- promotes glycogen storage and synthesis
- promotes fatty acid/TAG synthesis
What are the main symptoms of type 1 diabetes?
- polyuria
- polydipsia
- hyperphagia
- fatigue and weakness
- weight loss
What does insulin do to adipose tissue?
- inhibits fat breakdown
- encourages chylomicron uptake of TAG
- promotes TAG storage in adipocytes
Where is insulin degraded?
Liver, kidneys, placenta
Where does pre-proinsulin become pro insulin?
ER
What is the half life of insulin?
3-5 minutes
Which hormones can lower or increase plasma glucose levels?
Only insulin can lower plasma glucose. Hormones that can increase plasma glucose: - adrenaline - glucagon - cortisol - growth hormone
What is the pathway for producing fatty acids from G-6-P?
G-6-P –> pyruvate –> acetyl CoA –> fatty acids
How does the liver regulate glucose in the fed state?
Liver converts glucose to glucose-6-phosphate. The liver converts G-6-P back to glucose to maintain blood glucose levels.
G-6-P can be used to make: glycogen, pentose phosphate for DNA/RNA, and fatty acids.
What are the endocrine effects of insulin?
- promotes glucose uptake in adipose/liver
- promotes glycogen synthesis in liver/muscle
What is insulin?
A major anabolic hormone.
What does proinsulin do?
- longer half life than insulin
- responsible for 8% of insulin’s activity
degraded in kidney
What receptor allows for glucose uptake in beta cells?
GLUT2 in rodents, GLUT1 and GLUT3 in humans
In a healthy person, what is the plasma glucose level?
4-5.5mM
