Endocrine Control Of Metabolism Flashcards
(18 cards)
What is the significance of plasma glucose?
Plasma glucose concentration is remarkably constant at around 5 mmol/L, which is important as the 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 to maintain constant plasma glucose levels.
What are the two phases of metabolism?
1) storage of nutrients in the absorptive stage (fed state)
2) 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 (somatotrophin)
What are some major effects of insulin?
It stimulates nutrient storage:
- the uptake of glucose by skeletal muscle, adipose and other tissues
- glycogen synthesis in the liver and skeletal muscle
- uptake of fatty acids and amino acids
It also inhibits nutrient release:
- inhibits release of glucose from the liver (hepatic glucose production)
- inhibits fat and protein breakdown (lipolysis and proteolysis)
What are some effects of the counter-regulatory hormones?
They stimulate pathways leading to energy release.
GLUCAGON: has principal effects in the liver
- stimulates hepatic glucose production
ADRENALINE (and sympathetic NS)
- stimulates hepatic glucose production
- stimulates lipolysis (release of fatty acids from adipose tissue stores)
CORTISOL:
- stimulates hepatic glucose production
- stimulates proteolysis (the release of amino acids from bosy proteins [skeletal muscle] )
What are some metabolic pathways serving as energy storage?
GLYCOGENESIS: the synthesis of glycogen from glucose
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?
GLYCOGENOLYSIS: the release of glucose from glycogen stores
GLUCONEOGENESIS: the de novo synthesis of glucose from non-carbohydrate substrates
LIPOLYSIS: the release of fatty acids from triglyceride breakdown
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?
The immediate response is glucagon release from the pancreas.
The plasma glucose is detected in the pancreas itself, and the response is to turn up the rate of glucagon secretion from pacreatic endocrine cells called alpha cells.
What are the body’s defences against hypoglyceamia (ie. starvation) (in the short, medium and long-term)?
In the short-term:
- glucagon
- adrenaline
- sympathetic NS
In the medium-term:
- Ketogenesis: the fat reserves provide a partial substitute for glucose, sparing muscle tissue from 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 body’s defences against hyperglyceamia?
What are the two types of hyperglycaemia?
HOW INSULIN ACTS:
- it stimulates glucose uptake by tissues
- it inhibits hepatic glucose production
The lack of insulin action leads to hyperglycaemia, diabetes mellitus.
TYPE I DM: insulin deficiency
TYPE II DM: insulin insufficiency combined with insulin resistance
What are some major insulin-sensitive tissues, and what processes are affected by insulin?
INSULIN STIMULATES:
1) LIVER: glycogenesis, glycolysis, lipogenesis
2) ADIPOSE TISSUE: glucose uptake, free fatty acid uptake, lipogenesis
3) MUSCLE: glucose uptake, amino acid uptake, glycogenesis
INSULIN INHIBITS:
1) LIVER: glycogenolysis, gluconeogenesis
2) ADIPOSE TISSUE: lipolysis
Insulin is there to LOWER glucose blood levels.
Describe major metabolic pathways in adipose tissue (in terms of energy balance).
In times of positive energy balance, insulin stimulates uptake (LPL, GLUT4).
In times of negative energy balance, counter-regulatory hormones stimulate lipolysis and the release of FFA to the circulation. From there, bound to plasma proteins, they can be distributed to tissues for uptake and energy metabolism.
Describe glucose and amino acid metabolism in the liver.
Ketogenic amino acids (converted into Acyl CoA or Aceto-Acyl CoA) can give further rise to ketone bodies or fatty acids (KETOGENESIS).
Glucogenic amino acids are converted into pyruvate or citric acid cycle intermediates. The net synthesis of glucose from these is possible via phosphoenol pyruvate.
Oxaloacetate is converted to phosphoenolpyruvate (PEP) by the enzyme PEP carboxykinase (PEPCK).
Describe fatty metabolism in the liver (how insulin inherently inhibits β-oxidation).
In β-oxidation, fatty acids are converted to fatty Acyl-CoA, then to Acetyl-CoA (in the mitochondria). Acetyl CoA can be used to generate ATP via the TCA. However, if in excess, Acetyl-CoA goes instead into ketogenesis.
Glucose is also converted to Acetyl CoA. If in excess, (of requirement for ATP generation), and in the presence of insulin, Acetyl CoA goes instead into lipogenesis, back to fatty acids (which will then be esterifies to form triglycerides).
The first intermediate in lipogenesis is Malonyl-CoA, which then goes through further intermediates to produce fatty acids. Malonyl-CoA also has the effect of inhibiting CPT (carnitine-palmitoyl transferase), which is required to get fatty Acyl-CoA into mitochondria for oxidation (or ketogenesis).
Thus, insulin indirectly inhibits β-oxidation.
Describe how fat metabolism and ketogenesis relate.
Fatty acids entering the liver may be esterified for transport and storage as triglycerides, or enter the mitochondria for β-oxidation.
β-oxidation of fatty acids produces Acetyl-CoA. The Acetyl-CoA may enter the TCA cycle, or enter ketogenesis, depending on the body’s nutritional/ hormonal status.
Ketogenesis is the synthesis of acetoacetate and hydroxybutarate (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), the buffering capacity is overwhelmed.
This means there is decreased serum bicarbonate, which leads to diabetic ketoacidosis (normally, ketones, which are acids, are buffered by the blood).
This causes deep sighing (Kussmaul) respiration.
