Efectos Metabólicos de la Insulina y el Glucagón

Question 1

four main tissues play a dominant role in fuel metabolism ?

Answer 1

liver, adipose, muscle, and brain

Question 2

communication between tissues mediated by ?

Answer 2

nervous system, availability of circulating substrates, and variation in level of plasma hormones

Question 3

integration of ENERGY METABOLISM integrated primarily by ?

Answer 3

two peptide hormones: insulin and glucagon (in response to changing substrate levels in the blood), with catecholamines epinepherine and norepinepherine (in response to neural signals) playing a supporting role

Question 4

kind of metabolic effects of insulin ?

Answer 4

ANABOLIC !! e.g. synthesis of glycogen triacylglycerols (TAG’s) protein

Question 5

insulin secretion is increased by ?

Answer 5

increase in glucose, amino acids, and gastrointestinal peptide hormones

Question 6

explain the proportionality between glucokinase 4 phosphorylation activity and the concentration of glucose in the blood?

Answer 6

proportionality results from: 1) lack of direct inhibition of glucokinase by G-6-P, its product. 2) high Km (low affinity) of the enzyme that creates a sigmoidal relationship between velocity of the reaction and substrate concentration and endows hexokinase 4 its ‘glucose-sensing’ ability.

Question 7

how exactly does glucose-dependent release of insulin happen in the blood?

Answer 7

it is mediated through a rise in calcium concentration in beta cells. glucose taken into beta cells is phosphorylated and metabolized –> ATP produced –> ATP-sensitive potassium (K+) channels close, causing depolarization of the plasma membrane, opening of voltage gated Ca+ channels and influx of Ca+ into the cell. Ca+ causes vesicles containing insulin to be exocytosed from the beta cell .

Question 8

sulfonylureas are oral agents prescribed for diabetes type 2 patients. how do they function ?

Answer 8

they function by increasing insulin secretion by closing ATP-dependent K+ channels –> membrane depolarized –> voltage gated Ca+ channels open –> Ca+ influx causes insulin-cargoed vesicles to be exocytosed from the beta cell.

Question 9

role of catecholamines in energy metabolism?

Answer 9

they call for rapid mobilization of energy-yielding fuels like glucose from the liver (via glycogenolysis or gluconeogenesis) and fatty acids from adipose tissue (via lipolysis).

Question 10

primary metabolism regulator in case of emergency ?

Answer 10

the sympathetic nervous system takes over regulating blood glucose concentration during emergencies e.g. fight or flight rather than peptide hormones insulin and glucagon.

Question 11

mention the effect of the following on the release of insulin: #amino acids and fatty acids #epinepherine #glucose

Answer 11

amino acids and fatty acids –> promote insulin release epinepherine –> halts insulin release glucose –> promotes insulin release

Question 12

effects of insulin most prominent on three tissues. identify the 3 tissues along with the insulin effect on them #carbohydrate metabolism.

Answer 12

liver, muscle, adipose. REMEMBER: insulin always calling for SAVING on energy # liver and muscle, insulin increases glycogen synthesis. # muscle and adipose, insulin increases glucose uptake by increasing the number of GLUT 4 transporters. #liver, insulin decreases production of glucose via inhibition of glycogenolysis and gluconeogenesis.

Question 13

coordinated effect of insulin on adipose tissue?

Answer 13

reduction in release of fatty acids by inhibiting the activity of hormone-sensitive lipase, which degrades lipids in adipose tissues (TAG’s into fatty acids). #increases transport and metabolism of glucose into adipocytes, providing glycerol-3-phosphate substrate for TAG synthesis. #increases the expression of the gene for lipoprotein lipase in adipose tissue, providing fatty acids for esterification to the glycerol. # promotes the conversion of glucose to TAG in the liver. the TAGs are secreted in VLDLs.

Question 14

effect of insulin on protein synthesis?

Answer 14

stimulates the entry of amino acids into cells and protein synthesis *via activating translation initiation factors.

Question 15

receptor regulation of insulin ?

Answer 15

elevated levels of insulin promote the degradation of receptors, thereby decreasing the number of surface receptors. *downregulation*

Question 16

compare and contrast the time course of insulin action regarding different targets.

Answer 16

most immediate response is an increase of glucose transport into adipocytes, skeletal, and cardiac muscle cells that occurs within seconds of insulin binding to membrane receptors. #insulin-induced increase in the amount of many enzymes such as glucokinase, pyruvate kinase, ACC , fatty acid synthase, requires hours to days. thses changes reflect an increase in gene expression through increased transcription.

Question 17

briefly mention the chief effects of insulin on #Carb metabolism #lipid metabolism #protein synthesis

Answer 17

CARBS: glycogen synthesis in liver and muscle; high glucose uptake by muscle and adipose via GLUT 4; inhibits production of glucose via glycogenolysis and gluconeogenesis #LIPIDS: halt hormone-sensitive lipase; activate lipoprotein lipase to provide free fatty acids for esterification; TAG synthesis in liver to be carried in VLDLs into adipocytes; higher uptake of glucose in adipocytes –> provide glycerol-3-phosphate for TAG backbone #PROTEINS: stimulate entry of amino acids into cells and protein synthesis.

Question 18

insulin Vs. Glucagon

Answer 18

insulin: body high on energy –> metabolize glucose in headquarters (liver) –> STORE that shit outside ANABOLISM # glucagon: body low on energy –> avoid metabolizing glucose in headquarters–> rather use available energy to provide glucose elsewhere e.g. glycogenolysis and gluconeogenesis

Question 19

what stimulates glucagon secretion?

Answer 19

low blood glucose levels is primary stimulus. elevated glucagon prevents hypoglycemia

Question 20

amino acids and glucagon secretion?

Answer 20

amino acids derived from a meal containing protein stimulate glucagon release. glucagon protects against hypoglycemia that would otherwise occur after increased insulin secretion following a protein-rich meal.

Question 21

catecholamines and glucagon?

Answer 21

during periods of physiologic stress, where catecholamines are produced, glucagon levels are elevated regardless of the concentration of blood glucose, in anticipation of increased glucose use.

Question 22

effects of the following on glucagon secretion? #amino acids #epinepherine #glucose and insulin

Answer 22

amino acids > stimulate glucagon secretion #epinepherine> stimulate glucagon secretion glucose and insulin> inhibit glucagon secretion

Question 23

glucagon and CARB metabolism ?

Answer 23

immediate rise in blood glucose after glucagon secretion due to breakdown of liver glycogen stores and hepatic gluconeogenesis

Question 24

glucagon on LIPID metabolism ?

Answer 24

inhibition of ACC; fatty acid synthesis is halted #glucagon (along with catecholamines primarily)activate hormone sensitive lipase to liberate free fatty acids to be transported into the liver to be oxidized into acetyl coA for the synthesis of ketone bodies.

Question 25

glucagon on protein metabolism?

Answer 25

glucagon increases liver uptake of amino acids supplied by the muscles. amino acids in the liver provide carbon skeletons for gluconeogenesis –> blood amino acids decrease

Question 26

how does insulin get into cells?

Answer 26

insulin binds to its receptor on cell membrane –> activation of receptor’s tyrosine kinase activity –> autophosphorylation of specific tyrosine residues –> cascade of cell signaling responses –> recruitment of glucose transporters from intracellular pool to cell membrane.

Question 27

summarize effect of glucagon onto the cell ?

Answer 27

glycogenolysis #gluconeogenesis #fatty acid oxidation #subsequent production of ketone bodies #higher uptake of amino acids #DECREASE in glycogenesis

Question 28

how does glucagon enter hepatocytes ?

Answer 28

glucagon binds GPCR –> activates adenylyl cyclase –> activates cAMP –> activates cAMP -dependent PKA –> phosphorylation/dephosphorylation cascades –> versatile biologic effects

Question 29

symptoms of hypoglycemia ?

Answer 29

1# CNS symptoms including confusion, aberrant behavior, or coma 2# simultaneous blood glucose level equal to 40 mg/dI 3# symptoms being resolved within minutes of administering glucose MEDICAL EMERGENCY due to absolute requirement of CNS for continuous supply of bloodborne glucose to serve as fuel for energy metabolism. transient hypoglycemia –> cerebral dysfunction prolonged hypoglycemia –> brain death

Question 30

most important hormone changes in combating hypoglycemia ?

Answer 30

elevated glucagon and catecholamines combined with diminished release of insulin.

Question 31

explain alcohol-related hypoglycemia

Answer 31

Question 32

explain why chronic alcohol consumption can result in alcoholic fatty liver.

Answer 32

normally, under hypoglycemic conditions, glucagon stimulates the release of fatty acids from the adipocytes into the liver, where they are oxidized into acetyl coA and converted into ketone bodies. under chronic alcohol consumption, the NAD+/NADH ratio necessary for oxidation is very low, while hepatic lipogenesis is actually increased due to the availability of fatty acids and NADH (decreased catabolism). the increased production of TAGs in the liver with impaired formation or release of VLDLs lead to alcoholic fatty liver.