Endocrine Metabolism

Question 1

energy metabolism - defined

Answer 1

*the way that the body creates energy via combustion of carbohydrates, amino acids, and fat

Question 2

energy metabolism - key players

Answer 2

1. BRAIN: regulates energy intake - hunger, satiety, food-seeking behaviors
2. GUT: important in digestion, absorption, and transport of food/energy
3. LIVER, MUSCLE, ADIPOSE TISSUE: critical in energy storage & metabolism

Question 3

BRAIN & regulation of energy metabolism

Answer 3

*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

Question 4

types of metabolic fuels & organ usage

Answer 4

*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

Question 5

regulation of energy metabolism - anabolic vs. catabolic states

Answer 5

*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

Question 6

what happens when you eat carbohydrates?

Answer 6

*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

Question 7

glucokinase

Answer 7

*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

Question 8

anabolic (fed) state - overview

Answer 8

*governed by INSULIN; high insulin, low glucagon levels;
*food intake stimulates insulin release → lower blood glucose

Question 9

anabolic (fed) state - short term energy storage

Answer 9

*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

Question 10

anabolic (fed) state - long term energy storage

Answer 10

*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

Question 11

what happens when you fast?

Answer 11

*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

Question 12

catabolic (fasting) state - overview

Answer 12

*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

Question 13

glycogenolysis - defined

Answer 13

*the breakdown of glycogen back into glucose (during the fasting state)
*occurs in liver and muscle

Question 14

gluconeogenesis - defined

Answer 14

*the generation of glucose from amino acids
*occurs in liver

Question 15

proteolysis - defined

Answer 15

*proteins are broken down into amino acids (can enter gluconeogenesis)

Question 16

lipolysis - defined

Answer 16

*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

Question 17

energy sources in the catabolic state

Answer 17

1. carbohydrates are metabolized for energy FIRST (short-term energy needs)
2. during fasting, high-energy free fatty acids are used for energy
3. during prolonged starvation, there is ongoing fat depletion and then amino acids are mobilized from proteins in the body

Question 18

ketogenesis - defined

Answer 18

*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

Question 19

endocrine pancreas - overview

Answer 19

*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

Question 20

insulin - overview

Answer 20

*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

Question 21

glucagon - overview

Answer 21

*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

Question 22

somatostatin - overview

Answer 22

*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

Question 23

insulin-dependent glucose transporter

Answer 23

*GLUT4: require insulin in order to bring glucose into cells
-found in adipose tissue and striated muscle

Question 24

pharmacokinetics of insulin

Answer 24

*glucose is the most potent stimulant of insulin release
*there is also some basal insulin secretion that occurs all the time

Question 25

insulin release pathway

Answer 25

1. rising blood glucose levels → glucose enters the pancreatic beta cell through GLUT2 transporter
2. glycolysis generates ATP
3. ATP closes ATP-sensitive K channels
4. beta cell depolarizes, opening voltage-gated Calcium channels so Ca enters the cell
5. triggers insulin exocytosis from the cell into the bloodstream

Question 26

sulfonylurea drugs

Answer 26

*bind at the ATP-sensitive K channel to cause MORE insulin release
*helpful in pts with type 2 DM

examples: glipizide, glyburide

Question 27

insulin receptor binding

Answer 27

*skeletal muscle and adipose tissue are dependent on insulin for glucose uptake
1. insulin binds a tyrosine kinase receptor
2. binding leads to insertion of GLUT4 glucose transporters in skeletal muscle + adipose tissue, allowing for glucose to move into these cells for use

note - exercise also increases GLUT4

Question 28

impact of insulin on glucagon & somatostatin

Answer 28

*as insulin moves to exit the islet, it passes over glucagon-releasing alpha cells and somatostatin-releasing delta cells → INHIBITION of glucagon & somatostatin secretion
*an example of PARACRINE activity

Question 29

insulin sensitivity is decreased by:

Answer 29

*stress
*hormones (cortisol, growth hormone)
*free fatty acids
*cytokines (TNF-alpha)
*changes in receptors

Question 30

glucagon secretion

Answer 30

*LOW blood sugars STIMULATE glucagon secretion
*high blood sugars inhibit glucagon secretion (and stimulate insulin secretion)

Question 31

glucagon action

Answer 31

*acts at a G protein-coupled receptor via cAMP
*target = liver
*functions: RAISE BLOOD GLUCOSE BY:
1. promoting glycogenolysis
2. enhancing gluconeogenesis
3. promoting lipolysis & ketogenesis

Question 32

GLP-1 - overview

Answer 32

*aka glucagon-like peptide-1
*increases glucose-stimulated insulin release (an INCRETIN)
*increases beta-cell hypertrophy and growth
*can normalize glucose in non-insulin dependent diabetes

Question 33

ghrelin - overview

Answer 33

*the “hunger hormone”
*produced by gastric cells; release is triggered by an empty stomach
*stimulates appetite by acting on the hunger center in the hypothalamus
*increased during starvation, fasting, weight loss, sleep deprivation

Question 34

leptin - overview

Answer 34

*a “satiety hormone”
*acts on the hypothalamus to decrease appetite/food intake
*made in adipose tissue; increased total adipose tissue mass increases plasma leptin
*if you have no leptin or are resistant to leptin, you don’t experience appetite suppression → hyperphagia