Endocrine control of metabolism Flashcards
(23 cards)
What are the circulating nutrients?
Glucose Fatty acids (FFA, NEFA) Amino acids Ketone bodies Lactate
What are the stored nutrients?
Glycogen
Triglycerides (TG, TAG)
Body proteins
What is the normal level of plasma glucose?
5 mmol L-1
What is too low glucose levels called?
Hypoglycemia: ultimately coma and death
< ~2.5 mmol L-1 is critical
What is too high glucose levels called?
Hyperglycemia: chronic exposure to raised glucose concentrations leads to protein damage via non-enzymatic glycation
What is the 60/40/20 rule?
60% of body weight is water
40% of body weight is intracellular water
20% of body weight is extracellular water
What are the sources of plasma glucose?
- Diet
- Organs that can export glucose into the circulation
Diet: up to 3000 mmol day-1
What prevents plasma glucose surging after a meal and plummeting between meals?
Hormones regulate the integration of carbohydrate, fat and protein metabolism to maintain constant plasma glucose levels.
What are the two phases of metabolism?
Absorptive phase (fed state) - storage of nutrients Fasting phase (between meals) - release of nutrients
What hormones regulate metabolic pathways promoting energy storage or release?
Insulin: promotes storage, decrease in plasma glucose levels
Counter-regulatory hormones: promote nutrient release, raise plasma glucose.
- Glucagon
- Adrenaline
- Cortisol, growth hormone (somatropin)
What are the major effects of insulin?
Stimulates nutrient storage:
- Uptake of glucose by skeletal muscle, adipose and other tissues
- Glycogen synthesis in liver and skeletal muscle
- Uptake of FA and amino acids
Inhibits nutrient release:
- Inhibits release of glucose from liver (hepatic glucose production)
- Inhibits fat and protein breakdown (lipolysis and proteolysis)
What are the major effects of counter-regulatory hormones?
Stimulate pathways leading to energy release
Glucagon: principal effects in liver
-Stimulates hepatic glucose production
Adrenaline (and sympathetic NS)
- Stimulates hepatic glucose production
- Stimulates lipolysis: a release of FA from adipose tissue stores
Cortisol
- Stimulates hepatic glucose production
- Stimulates proteolysis: a release of amino acids from body proteins (skeletal muscle)
What are the metabolic pathways for energy storage?
Glycogenesis -Synthesis of glycogen from glucose Lipogenesis -Synthesis of FA from acetyl CoA Triglyceride synthesis -Esterification of FA for storage as TG
What the are metabolic pathways for energy release?
Glycogenolysis -Release of glucose from glycogen stores -De novo synthesis of glucose from non-carbohydrate substrates Lipolysis -Release of FA from TG breakdown Beta-oxidation -FA to Acetyl CoA Ketogenesis -Production of ketone bodies from Acetyl CoA
What senses changes in blood glucose levels?
Endocrine cells in the pancreas, cells in the brain
What are the metabolic responses to hypoglycemia?
Low glucose detected by the endocrine cells in the pancreas and it releases glucagon and inhibits insulin secretion. glucagon stimulates the liver to increase hepatic glucose output, both glycogenolysis and gluconeogenesis.
Brian cells will also detect and activate the sympathetic pathway and activate adrenal medulla which will also increase circulating epinephrine.
What are the defences against hypoglycemia?
In the short-term
- Glucagon
- Epinephrine
- Sympathetic NS
In the medium-term
-Ketogenesis: fat reserves can provide a partial substitute for glucose, sparing muscle tissue from the destruction that would otherwise be needed to provide amino acid substrates for gluconeogenesis
In the long-term
-Cortisol stimulates proteolysis to supply amino acid substrates for gluconeogenesis
What are the defences against hyperglycemia?
Insulin
-Stimulates glucose uptake by tissues
-Inhibits hepatic glucose production
Lack of insulin action leads to hyperglycaemia, diabetes mellitus
-Type 1 DM: insulin deficiency
-Type 2 DM: insulin insufficiency combined with insulin resistance
What does insulin stimulate?
Liver
- glycogenesis
- glycolysis
- lipogenesis
Adipose tissue
- glucose uptake
- free fatty acid uptake
- lipogenesis
Muscle
- glucose uptake
- amino acid uptake
- glycogenesis
What does insulin inhibit?
Liver
- glycogenolysis
- gluconeogenesis
Adipose tissue
-Lipolysis
Explain fat metabolism and ketogenesis
Fatty acids entering the liver may be esterified for transport and storage as TG, or enter mitochondria for beta-oxidation
Beta-oxidation of FA produces acetyl CoA
Acetyl CoA may enter TCA cycle, or enter ketogenesis, depending on the nutritional/hormonal status
Ketogenesis: synthesis of acetoacetate and hydroxybutyrate (ketone bodies) from Acetyl Co A
Ketone bodies are freely transported in the bloodstream, reconverted back to acetyl CoA, in the brain and other tissues, and metabolised in TCA cycle for energy
What is ketogenesis?
In the liver, oxidation of fatty acids and gluconeogenesis can compete for substrates
Beta-oxidation of FA produces acetyl CoA, which combines with oxaloacetate (OAA) to form citrate, entering the TCA cycle for complete oxidative phosphorylation
However, OAA is also used as a substrate in gluconeogenesis
In absence of sufficient OAA, acetyl CoA builds up and is funnelled into ketogenesis
Ketone bodies are acids: excess in circulation overwhelm buffering capacity of blood, leading to metabolic acidosis
What is diabetic ketoacidosis?
Express production fo ketone bodies which are mildly acidic
In insulin deficiency (i.e. type 1 diabetes mellitus) the buffering capacity is overwhelmed
Decreased serum bicarbonate
Diabetic ketoacidosis
Normally ketones (acids) are buffered by the blood
deep sighing (Kussmaul) respiration
in the absence of insulin, Acetyl CoA turns into ketone bodies instead of making citrate with oxaloacetate.
