Diabetes Flashcards
What does insulin inhibit?
- Gluconeogenesis
- Glycogenlysis
- Ketogenesis
- Lipolysis
- Proteolysis
What does insulin signal?
Plenty/fed state
What does insulin promote?
- Glycolysis
- Glycogen synthesis
- Glucose uptake (use of glucose)
- Fatty acid synthesis
- Protein synthesis
What tissues particularly rely on glucose as an energy source?
Brain, RBCs
What is effect of glucagon on glycolysis?
Inhibits it
What is effect of glucagon on gluconeogenesis?
Stimulates it
What is effect of glucagon on glycogenolysis?
Stimulates
How does insulin promote glycolysis?
Activates phosphofructokinase and pyruvate kinase
How does insulin promote the storage of glucose as glycogen?
Inhibits glycogen phosphorylase
How does insulin promote the uptake and use of glucose by cells?
Promotes movement of GLUT4 to cell membrane to facilitate glucose entry
How does insulin promote the conversion of glucose to triacylglycerols?
Stimulates pyruvate dehydrogenase –> increases conversion of pyruvate to acetyl CoA
Stimulates acetyl CoA carboxylase which catalyses the first step in fatty acid synthesis
Why does low blood glucose lead to increased acetyl CoA?
Glucagon leads to break down of triacylglycerol to form free fatty acyl CoA –> acetyl CoA
In diabetes 1, why is blod glucose high?
Insulin levels are low
- No movement of GLUT4 so no uptake
- Glycogen breakdown and gluconeogenesis stimulated (body reacts as if its starving)
In diabetes, why does glucose appear in urine?
Blood glucose exceeds the concentration that can be reabsorbed in the proximal tubule
In diabetes, why is muscle protein broken down?
Insulin normally inhibit protein breakdown and promotes protein synthesis (at the level of translation)
Without insulin, protein breakdown occurs and the amino acids provide substrates for gluconeogenesis
In diabetes, why are ketones formed?
Fatty acid breakdown accelerated without insulin
This causes high conc of Acetyl CoA
TCA intermediate levels are low due to their removal for gluconeogenesis (which is going on at same time) so Acetyl CoA builds up as it can’t feed easily into Krebs cycle
Ketones are formed from acetyl CoA which can be used by brain etc for energy during prolonged fasting
What are dangers of high levels of ketone bodies?
Risk of ketoacidosis
What is ketoacidosis?
Drop in pH of blood due to circulating ketones
At pH <7.0, many enzymes are affected
Can be fatal
What is HbA1C?
Glycated form of Hb (glucose added to Hb non-enzymatically)
What is the rate of glycation of Hb determined by?
Prevailing glucose conc during life of erythrocyte
How can measuring HbA1C aid in monitoring diabetes?
Test provides insight into average blood glucose conc over period of time instead of ‘spot test’
High levels indicates diabetes
What is the main cause of death in diabetes related to?
Macrovascular complications (myocardial infarcation, stroke and peripheral vascular disease)
How can hyperglycaemia lead to long term dangers?
- Increased use of minor metabolic pathways
- Glycation
Why does hyperglycaemia lead to increased use of minor pathways (e.g. polyol pathway)
If glucose levels are abnormally high, polyol pathway may occur
Polyol pathway –> some tissues have the enzymes to convert glucose to sorbitol and fructose
What are the dangers of sorbitol and fructose?
These are osmotically active and lead to swelling
Sorbitol may be toxic
What is glycation?
The covalent attachment (non-enzymatic) of a sugar to a protein or lipid.