Endocrine Control & Metabolism Flashcards
What is the significance of keeping plasma glucose at 5mmol/l?
Brain depends on glucose metabolism
What is the source of our body glucose?
- diet
- organs that can export glucose into the circulation
What prevents plasma glucose surging after a meal and plummeting between meals?
Hormones regulate the integration of carbohydrate, fat and protein metabolism
What are the two phases of metabolism?
- storage of nutrients in the absorptive stage (fed state)
- release of nutrients in the fasting phase (between meals)
List some counter-regulatory hormones (those that promote nutrient release, raise plasma glucose).
- glucagon
- adrenaline
- cortisol, growth hormone
What are some major effects of insulin on stimulating nutrient release?
- Uptake of glucose by skeletal muscle, adipose and other tissues
- Glycogenesis in the liver and skeletal muscle
- Uptake of fatty acids and amino acids
What are some major effects of insulin on inhibiting nutrient release?
- Inhibits hepatic glucose production
- Inhibits lipolysis and proteolysis
What are some effects of the counter-regulatory hormones? PART 1
Stimulate pathways leading to energy release.
GLUCAGON: has principal effects in the liver
- stimulates hepatic glucose production
What are some effects of the counter-regulatory hormones? PART 2
ADRENALINE (and sympathetic NS)
stimulates hepatic glucose production
stimulates lipolysis (release of fatty acids from adipose tissue stores)
CORTISOL:
- same as adrenaline but stimulates proteolysis (NOT LIPOLYSIS)
What are some metabolic pathways serving as energy storage?
GLYCOGENESIS
LIPOGENESIS: the synthesis of fatty acids from Acetyl CoA
TRIGLYCERIDE SYNTHESIS: the esterification of fatty acids for storage as triglycerides
What are some metabolic pathways serving as energy release? PART 1
GLYCOGENOLYSIS
GLUCONEOGENESIS: de novo synthesis of glucose from non-carbohydrate substrates
LIPOLYSIS: release of fatty acids from triglyceride breakdown
What are some metabolic pathways serving as energy release? PART 2
β-OXIDATION: the conversion of fatty acids from Acetyl CoA
KETOGENESIS: the production of ketone bodies from Acetyl CoA
What is the metabolic response to hypoglyceamia?
- Plasma glucose is detected in the pancreas
- Increase in glucagon secretion from alpha cells.
What are the body’s defences against hypoglycemia in the short term?
- glucagon
- adrenaline
- sympathetic NS
What are the body’s defences against hypoglycemia in the medium term?
- Ketogenesis: the fat reserves provide a partial substitute for glucose
Why is ketogenesis useful?
HINT - Think about what ketogenesis produces and what would happen if ketogenesis were to fail
- Produces fatty acids
- If ketogenesis didn’t happen, skeletal muscle would be broken down to form amino acid substrates for gluconeogenesis
What are the body’s defences against hypoglycemia in the long term?
- Cortisol stimulates proteolysis to supply amino acid substrates for gluconeogenesis.
What are the body’s defences against hyperglyceamia?
INSULIN
- Stimulates glucose uptake by tissues
- Inhibits hepatic glucose production
What are the two types of hyperglycaemia?
TYPE I Diabetes: insulin deficiency
TYPE II Diabetes: insulin insufficiency combined with insulin resistance
What are some major insulin-sensitive tissues, and what processes are affected by insulin? PART 1
INSULIN STIMULATES:
- LIVER: glycogenesis, glycolysis, lipogenesis
- ADIPOSE TISSUE: glucose uptake, free fatty acid uptake, lipogenesis
- MUSCLE: glucose uptake, amino acid uptake, glycogenesis
What are some major insulin-sensitive tissues, and what processes are affected by insulin? PART 2
INSULIN INHIBITS:
- LIVER: glycogenolysis, gluconeogenesis
- ADIPOSE TISSUE: lipolysis
Describe major metabolic pathways in adipose tissue during positive energy balance.
Insulin stimulates uptake
Describe major metabolic pathways in adipose tissue during negative energy balance.
- Counter-regulatory hormones stimulate lipolysis and the release of FFA to circulation.
- Distributed to tissues for uptake and energy metabolism.
Describe glucose and amino acid metabolism in the liver. PART 1
Ketogenic amino acids (converted into Acyl CoA or Aceto-Acyl CoA) can give rise to ketone bodies or fatty acids (KETOGENESIS).
Describe glucose and amino acid metabolism in the liver. PART 2
- Glucogenic amino acids are converted into pyruvate or citric acid cycle intermediates.
- Synthesis of glucose is possible via phosphoenol pyruvate (PEP).
- Oxaloacetate is converted to PEP by PEP carboxykinase (PEPCK).
Describe fatty metabolism in the liver (how insulin inherently inhibits β-oxidation). PART 1
In β-oxidation, fatty acids are converted to Acyl-CoA, then to Acetyl-CoA (in the mitochondria).
- Acetyl CoA can be used to generate ATP via the TCA.
- If in excess, Acetyl-CoA goes instead into ketogenesis.
Describe fatty metabolism in the liver (how insulin inherently inhibits β-oxidation). PART 2
- Glucose is converted to Acetyl CoA.
- If in excess and in the presence of insulin, Acetyl CoA goes instead into lipogenesis, back to fatty acids (which will then be esterified to form triglycerides).
Describe fatty metabolism in the liver (how insulin inherently inhibits β-oxidation). PART 3
- First intermediate in lipogenesis is Malonyl-CoA
- Malonyl-CoA inhibits CPT (carnitine-palmitoyl transferase), which is required to get fatty Acyl-CoA into mitochondria for oxidation (or ketogenesis).
Describe how fat metabolism and ketogenesis relate. PART 1
- Fatty acids entering the liver are esterified for transport and storage as triglycerides, or enter the mitochondria for β-oxidation.
Describe how fat metabolism and ketogenesis relate. PART 2
- β-oxidation of fatty acids produces Acetyl-CoA.
- Acetyl-CoA may enter the TCA cycle, or enter ketogenesis, depending on the body’s nutritional/ hormonal status.
Describe how fat metabolism and ketogenesis relate. PART 3
- Ketogenesis is the synthesis of ketone bodies from AcetylCoA.
- Ketone bodies are freely transported in the blood stream, reconverted back to Acetyl-CoA, in the brain and other tissues, and metabolised in the TCA cycle for energy.
Describe diabetic ketoacidosis.
- In insulin deficiencies (ie. type I diabetes mellitus), buffering capacity is overwhelmed.
- Decreased serum bicarbonate, which leads to diabetic ketoacidosis (normally, ketones, which are acids, are buffered by the blood).
