Endocrine Metabolism Control Flashcards
What is the typical concentration of plasma glucose and what happens if it becomes too low?
Plasma glucose conc ~5 mmol L-1
In a 70 kg male, 14 L extracellular water gives total of 14x5 = 70 mmol glucose.
The brain depends on glucose metabolism and consumes 30mmol/hr so low levels of it can be critical. Skeletal muscle consumes ~300 mmol/hr
Hypoglycemia can lead to coma and death. < ~2.5 mmol L-1 is critical
What are the 2 phases of glucose metabolism?
Storage of nutrients in the absorptive phase (fed state)
Release of nutrients in the fasting phase (between meals, aka postabsorptive phase)
Hormones regulate metabolic pathways promoting energy storage or release
Which hormones regulate the metabolism of glucose?
Insulin: promotes storage, decreases plasma glucose
Counter-regulatory hormones: promote nutrient release, raise plasma glucose
Glucagon
Adrenaline (epinephrine)
Cortisol, growth hormone (somatotrophin)
Glucagon and insulin are both pancreatic hormones and work together to maintain plasma glucose within limits
Describe insulin and its major effects
Insulin is synthesised and secreted by the islets of Langerhans in the pancreas.
Takes up glucose by skeletal muscle, adipose and other tissues
Synthesises glycogen in liver, skeletal muscle,
Takes up FA and amino acids
Inhibits nutrient and glucose from liver (hepatic glucose production)
Inhibits fat and protein breakdown (lipolysis and proteolysis)
What is the major effects of the counter regulatory hormones?
Glucagon: Stimulates hepatic glucose production
Adrenaline (and symp NS): Stimulates hepatic glucose production, and lipolysis: release of FA from adipose tissue stores
Growth hormone: Stimulates hepatic glucose production, lipolysis
Cortisol: Stimulates hepatic glucose production, lipolysis, and proteolysis: release of amino acids from body proteins (skeletal muscle)
Which metabolic pathways store energy?
Glycogenesis: Synthesis of glycogen from glucose
Lipogenesis: Synthesis of FA from acetyl CoA
Triglyceride synthesis: Esterification of FA for storage as TG
Which metabolic pathways release energy?
These metabolic pathways occur in the postabsorptive or fasting phase. This stops hypoglycaemia.
Glycogenolysis: release of glucose from glycogen stores
Gluconeogenesis: de novo synthesis of glucose from non-carbohydrate substrates
Lipolysis: release of FA from TG breakdown
Beta-oxidation in the mitochondria: FA to Acetyl Co A
Ketogenesis: production of ketone bodies from Acetyl CoA
Describe the metabolic responses to hypoglycaemia in the short term
The pancreas releases glucagon from alpha cells, which acts on the liver to release glucose
Hypoglycemia stimulates the brainstem and hypothalamus to increase symp outflow.
Increased symp outflow also acts on the adrenal medulla to release epinephrine, which stimulates the liver to release more glucose, and also stimulates alpha cells
What are the longer term defences against hypoglycaemia?
In the medium-term
Ketogenesis: fat reserves= partial glucose substitute, sparing muscle tissue from gluconeogenesis
In the long-term
Cortisol stimulates proteolysis to supply aa substrates for gluconeogenesis- this cannot go on forever as it destroys protein
What are the defences against hyperglycaemia?
Insulin stimulates glucose uptake by tissues
Inhibits hepatic glucose production
Lack of insulin action leads to hyperglycaemia, DM
Type 1 DM: insulin deficiency
Type 2 DM: insulin insufficiency combined with insulin resistance
Describe the major metabolic pathways in adipose tissue
In positive energy balance, insulin stimulates glucose uptake via GLUT4. It’s then converted into FA via lipogenesis. The glucose in the cell is then esterified to TGs for storage.
In negative energy balance, adrenalin stimulates lipolysis and FFA release. From there, bound to plasma proteins, they can be distributed to tissues for uptake and energy metabolism.
Describe the major metabolic pathways in muscle using a diagram
Describe the fate of glucose in the liver if there is high vs low insulin levels
High insulin/low glucagon: glucose is directed towards glycogen storage; when these are full glucose enters glycolysis and resulting Acetyl CoA is fed into lipogenesis.
Low insulin/high glucagon: AAs are diverted away from protein synthesis into gluconeogenesis.
A few AAs can be directly converted to Acetyl CoA (ketogenic AAs); these are fed into ketogenesis.
Describe ketogenesis in the liver
Glucose is converted to acetyl CoA. If in excess, w insulin, acetyl CoA forms malonyl CoA, which eventually produces FAs.
Malonyl CoA also inhibits CPT, which is required to get fatty acyl-CoA into mitochondria for oxidation (or ketogenesis). Thus, insulin indirectly inhibits B-oxidation/ketogenesis, but glucagon stimulates it
What is the importance of ketogenesis?
Ketone bodies exported from liver are reconverted back to acetyl CoA, in brain and other tissues, and metabolised in TCA cycle for energy.
Therefore, this conserves glucose in the fasting state
How can DM type 1 lead to diabetic ketoacidosis?
As glucose entry into adipose tissue is insulin dependent, severe insulin deficiency will mean TGs instead undergo lipolysis–> FA + glycerol.
FA –> ACoA via B-oxidation, and ACoA enters the TCA cycle
But, in severe insulin deficiency, hay too much ACoA, the TCA cycle becomes saturated and there won’t be enough OAA.
Therefore ACoA undergoes ketogenesis to form acidic ketone bodies–> DKA
