Endocrine Metabolism Flashcards
energy metabolism - defined
*the way that the body creates energy via combustion of carbohydrates, amino acids, and fat
energy metabolism - key players
- BRAIN: regulates energy intake - hunger, satiety, food-seeking behaviors
- GUT: important in digestion, absorption, and transport of food/energy
- LIVER, MUSCLE, ADIPOSE TISSUE: critical in energy storage & metabolism
BRAIN & regulation of energy metabolism
*glucose = primary supplier of brain ATP
*normal glucose = 70-120 mg/dL
*consequences of abnormal glucose:
-hyperglycemia → acute (DKA), chronic (damage to nerves, eyes, kidneys)
-hypoglycemia → impaired CNS function, headaches
types of metabolic fuels & organ usage
*carbohydrates → glucose
*fats → fatty acids + ketone bodies
*protein → amino acids
glucose is first choice for ALL organs; glucose is the ONLY fuel for RBCs, so they need a constant supply
regulation of energy metabolism - anabolic vs. catabolic states
*we must ensure an adequate energy supply at all times, despite not eating continuously, so we alternate between:
1. anabolic state (fed, absorptive): nutrient availability for immediate use + storage
2. catabolic state (fasted): limited nutrient intake, requires mobilization and use of stored energy supplies
*main hormones for regulation of these states = INSULIN and GLUCAGON
what happens when you eat carbohydrates?
*short term: available carbs are converted to glycogen (by glycogen synthase in process of glycogenesis) to be stored (we use glycogen for energy while fasting)
*when excess carbs are eaten: extra carbs are converted to triglycerides for storage; also stimulates protein synthesis
*hexokinase shunts glucose into the glycogen synthesis pathway for storage
glucokinase
*glucose sensor
*tells the body how much glucose is around
*insulin increase glucokinase; glucokinase in turn tells the pancreas how much insulin or glucagon to release
anabolic (fed) state - overview
*governed by INSULIN; high insulin, low glucagon levels;
*food intake stimulates insulin release → lower blood glucose
anabolic (fed) state - short term energy storage
*GLYCOGENESIS: formation of glycogen from glucose; glycogen stored in liver and muscles for later use
*mechanism: insulin stimulates glycogen synthase
*glycogen can be broken down later to release glucose (and to make ATP) = prevents hypoglycemia while fasting
anabolic (fed) state - long term energy storage
*LIPOGENESIS: formation of lipids/fatty acids from glucose
*occurs when the liver is saturated with glycogen
*triglycerides are the storage form of fat and comprise most of the body’s energy reserves
what happens when you fast?
*short term: BG falls and triggers pancreas to make glucagon; glucagon tells liver to start glycogenolysis to break down glycogen to glucose (via glycogen phosphorylase)
*long term: proteolysis, gluconeogenesis, lipolysis, ketogenesis
catabolic (fasting) state - overview
*governed by GLUCAGON; low insulin, high glucagon levels
*glucagon mobilizes and metabolizes carb and fat stores for energy → RAISES BLOOD SUGAR
*glucagon is inhibited by insulin and hypoglycemia
glycogenolysis - defined
*the breakdown of glycogen back into glucose (during the fasting state)
*occurs in liver and muscle
gluconeogenesis - defined
*the generation of glucose from amino acids
*occurs in liver
proteolysis - defined
*proteins are broken down into amino acids (can enter gluconeogenesis)
lipolysis - defined
*breakdown of triglycerides into free fatty acids and glycerol, ultimately generating ketones and glucose
*ketogenesis creates ketones from fatty acids which helps keep you alive, but can also be bad
energy sources in the catabolic state
- carbohydrates are metabolized for energy FIRST (short-term energy needs)
- during fasting, high-energy free fatty acids are used for energy
- during prolonged starvation, there is ongoing fat depletion and then amino acids are mobilized from proteins in the body
ketogenesis - defined
*conversion of fatty acids into ketones
*critical in starvation, preserves energy supply to brain, heart
*ketones (fat derived fuels used for energy generation when glucose availability is limited) = acetoacetate, acetone, beta-hydroxybutyrate
*excess ketones can cause ketoacidosis
endocrine pancreas - overview
*pancreas has 2 tissue types:
-endocrine = insulin, glucagon, somatostatin
-exocrine = digestive enzymes
*endocrine pancreas is composed of clusters of cells called islets of Langerhans, which contain 3 cell types:
-beta cells make insulin
-alpha cells make glucagon
-delta cells make somatostatin
insulin - overview
*an anabolic hormone secreted in response to eating that facilitates storage of carbs and fats
*a peptide hormone derived from proinsulin (a prohormone); made in beta cells
*proinsulin is cleaved to form insulin and c-peptide is a by-product; difficult to measure insulin levels in a blood test, so we measure c-peptide as a surrogate to evaluate endogenous insulin production
*insulin gene is on chromosome 11
*insulin is cleared by kidneys
glucagon - overview
*a catabolic hormone secreted in order to raise serum glucose by stimulating glycogenolysis and gluconeogenesis; primarily targets the liver
*made from proglucagon (which can also be cleaved into glucagon-like peptide-1 in intestinal cells, which lowers serum glucose)
*made inside alpha cells of pancreatic islet cells
*MOA: binds to GPCRs (Q alpha s subunit) → activate adenylyl cycle → increased cAMP
somatostatin - overview
*aka growth hormone inhibiting hormone
*produced by delta cells of the pancreatic islets
*polypeptide hormone
*inhibits growth hormone, prolactin, and regulates GI function
*inhibits release of insulin and glucagon
insulin-dependent glucose transporter
*GLUT4: require insulin in order to bring glucose into cells
-found in adipose tissue and striated muscle
pharmacokinetics of insulin
*glucose is the most potent stimulant of insulin release
*there is also some basal insulin secretion that occurs all the time
