Week 7-DM Flashcards
Describe what happens to glucose in the fed state
Describe what happens to make glucose in the fasted state?
Proteolysis
•Acetyl-CoA
Lipolysis
- Glycerol –> pyruvate
- FA –> Beta oxidation to acetyl-coa +/- KB
What are the causes of hypoglycaemia?
- Exertion/ exercise
- Fasting
- Excess exogenous insulin
- Insulinoma
-
Alcohol intake
- Increased endocrine pancreatic microcirculation –> increased insulin secretion
- Inhibits hepatic gluconeogenesis (reduced NADH)
What are the effects of hypoglycaemia in 4 catagories?
What can you do to remedy each catagory?
What strucutre does not contribute directly to blood glucose?
Muscle. Only liver glycogen is used for regulation of blood glucose
Muscle does contribute indirectly via proteolysis –> alanine & through transamination reactions –> deamination AA –> glucose
List some actions of insulin
- Stimulates glucose transport (m&at) (muscle, adipose tissue)
- Stimulates glycogen synthesis (l&m) (liver)
- Inhibits gluconeogenesis
- Stimulates protein synthesis
- Facilitates vasodilation
- Stimulates K+ –> cells
- Activates lipoogenesis
- Inhibits fatty acid oxidation (l&m)
- Inhibits lipolysis
LIst the glucose handling effects of insulin the muscle and liver
List some hormones that do the opposite of inuslin
Glucagon, adrenaline, cortisol
What is the effect of hypoglyceamia on the secretions of hormone that increase BG?
Glucose receptors in hypothalamus & glucose sensitive cells detect the hypoglyceamia
- Alpha cells –> increase glucagon
- Hypothalamus
- Sympathetic outflow
- Pituitary- anteriorly increases vasopression & Growth hormone and posteriorly ATCH –> cortisol
Give some causes of hyperglycaemia
Absolute absence of insulin T1DM:
- Pancreatic β-cells destroyed
- Dawn phenomenon (↑ cortisol)
T2DM Insulin resistance:
- Secreted but tissues insensitive
Stress- chronic high cortisol & adrenaline:
- –> Glycogenolysis in liver
List some of the effects/ what happens during DMT2
(think broadly- what hormones are decreases, what actions are decreases etc…)
What are some of the coplications arising from chronic hyperglyceamia?
- Non-enzymatic modifications of proteins by glucose- HBA1c
- Sorbitol pathway overactivity- formation of osmotically active metabolites
- Disturbance cellular redox state
- Impaired vasodilation
- Peripheral neuropathy- cataract, blindness, impaired kidney function
Insulin secretion is ___
Insulin secretion is biphasic
Describe the 1st insulin release phase
GLUT 2 has a high Km (15mM)
Glucose –> Gluose-6-P via glucokinase (Km of 10)
Acetyl-CoA inhibits K+ channel and enhances Ca2+ signalling
What gut hormones affect the release of inuslin and what does this cause?
CCK, GIP, GLP-1- Act on Beta cells
GIP/GLP increase lipogenesis and glycogenesis in muscles
What do delta cells secrete?
What type of hormone is this and what is its effect?
Somatotastin (peptide hormone that dampens both inuslin & glucagon)
What is the use of AA in normal conditions?
What is the use of AA during fasting/ post-op/ poorly controlled DM?
How is glucose distributed in the FED state
Glucose –> FA –> TG in liver. Packaged in VLDL to carry FA to muscle/ adipose tissue (TG converted to FA by lipoprotein lipase-LPL)
Gluocse also travels in chylomicrons from gut as TG again to muscle/adipose tissue (TG conversion to FA by lipoprotein lipase LPL)
How is glucose distributed in the fasting state/ DM?
•FA to liver –> KB which can be used by brain
- KB also used by muscle
•Decrease in LPL
What is the interaction in the development of inuslin resistance and DMT2?
Not all of the tissues are insulin resistant so this can lead to a slight hyperglycaemia. Pancrease detects this.
The liver continues to synthesise lipids and secrete them –> Hypertriglyceridaemia
Gluconeogensis increases (no inhibition via inuslin)–> Hyperglycaemia
–> B cell dysfunction & B cell failure
Outline some pharmacological stratergies aimed at preventing DM (think actions/ processes)
