Interorgan Metabolism

Question 1

fuel homeostasis

Answer 1

-taking in excess calories -> storage
-taking in too few calories -> nutrient release

Question 2

factors that control fuel homeostasis

Answer 2

1) tissue fuel metabolism (gluconeogenesis, glycogenolysis, glucose sparing, etc)
2) pancreatic hormones (insulin and glucagon)

Question 3

what cell type can ONLY use glucose as an energy source

Answer 3

red blood cells (RBCs)

Question 4

glucose sparing effect

Answer 4

saving glucose for utilization by RBCs by using other forms of energy (ketone bodies, etc) when glucose is short

Question 5

well-fed state

Answer 5

-high insulin levels (from beta cells) due to high levels of nutrients (glucose, amino acids, fatty acids)
-low glucagon
-stable glucose levels
-fatty acid and ketone body utilization are low

Question 6

organ metabolism in well-fed state

Answer 6

insulin regulates tissues:
-muscle: glycogen & protein synthesis
-liver: glycogen & triglyceride storage
-adipocytes: triglyceride storage

Question 7

calories stored in glycogen

Answer 7

2000 calories (can be used for glucose)

Question 8

calories stored in proteins

Answer 8

30,000 calories (can be used to make glucose and/or ketone bodies)

Question 9

calories stored in triglycerides

Answer 9

140,000 calories (fatty acids can be used to make ketone bodies; glycerol can be used to make glucose)

Question 10

overnight fasting state

Answer 10

-low insulin (because low nutrients)
-high glucagon [turns on glycogenolysis, lipolysis, and gluconeogenesis]
-glucose stable
-slightly increased fatty acid utilization
-slightly increased ketone utilization

Question 11

during overnight fast, what is the PRIMARY energy source

Answer 11

glycogen stores (~80% of energy)
[small amounts from amino acids and glycerol]

Question 12

1-3 day fast

Answer 12

-low insulin
-high glucagon
-stable glucose
-significantly increased fatty acid utilization
-significantly increased ketone utilization

Question 13

during 1-3 day fast, what is the PRIMARY energy source

Answer 13

glycogen stores are depleted, so… primary stores from proteolysis (releases amino acids for gluconeogenesis); triglyceride breakdown in fat and ketone body synthesis in liver increase too

Question 14

prolonged fasting state

Answer 14

-low insulin
-high glucagon
-stable glucose
-fatty acid utilization WAY up
-ketone body utilization WAY up
-*turned off proteolysis so we don’t waste away

Question 15

during prolonged fasting, what is the PRIMARY energy source

Answer 15

ketone bodies
-glucose is preserved for RBCs (glucose sparing effect)
-muscle proteolysis is shutdown

Question 16

how does the kidney contribute during prolonger fasting state

Answer 16

1) promotes reuptake of ketone bodies (conserves them)
2) can contribute to some gluconeogenesis

Question 17

overview - how does insulin regulate gene expression in the liver

Answer 17

*insulin suppresses transcription of gluconeogenic enzymes in the liver during a well-fed state

Question 18

details - how does insulin regulate gene expression in the liver

Answer 18

1) insulin binds its receptor and the activated receptor interacts with IRS
2) IRS binds to and activates a kinase
3) the kinase PHOSPHORYLATES FOXO
4) phosphorylated FOXO cannot enter nucleus and activate transcription of gluconeogenic enzymes

Question 19

overview - how does glucagon regulate gene expression in the liver

Answer 19

*glucagon promotes transcription of gluconeogenic enzymes in the liver during a fasting state

Question 20

details - how does glucagon regulate gene expression in the liver

Answer 20

1) glucagon binds its receptor
2) cAMP levels increase
3) cAMP activates PKA
4) PKA enters nucleus
5) C subunit of PKA phosphorylates CREB
6) CREB interacts with several transcription factors, including FOXO, which ACTIVATE TRANSCRIPTION OF GLUCONEOGENIC ENZYMES

Question 21

CREB

Answer 21

cAMP response binding protein; interacts with FOXO to activate transcription of gluconeogenic enzymes in a fasting state (when glucagon is present)

Question 22

type I diabetes characteristics

Answer 22

beta cells are destroyed, eliminating production of insulin; ketoacidosis is an acute complication
-frequently undernourished at onset of disease
-moderate genetic predisposition
-insulin always necessary

Question 23

type 2 diabetes characteristics

Answer 23

insulin resistance, combined with inability of beta cells to produce appropriate quantities of insulin (but some insulin still present); hyperosmolar state is a complication
-obesity at onset of disease
-VERY STRONG GENETIC PREDISPOSITION
-responsive to oral hypoglycemic drugs; insulin may not be necessary

Question 24

why is gluconeogenesis elevated in diabetes

Answer 24

insulin is not present to turn off transcription of gluconeogenesis enzymes (not phosphorylating FOXO); gluconeogenesis continues to make glucose, even in well-fed state, causing excess hyperglycemia

Question 25

ketoacidosis in type 1 diabetes

Answer 25

1) glucagon is dominant over insulin
2) *glucagon stimulates hormone sensitive lipase in the adipocytes
3) free fatty acids and glycerol released into blood
4) liver converts FFA to ketones & carnitine is elevated
5) ketones released into blood and attain high levels
6) protons released and pH starts to drop

Question 26

why is ketoacidosis a factor in T1D and not T2D

Answer 26

in T1D, the complete lack of insulin prevents glucose from being transported into cells, causing increased production of ketone body formation
-in T2D, there is still some insulin present so the glucose can still get into muscle and fat cells, decreasing likelihood of ketoacidosis

Question 27

hyperosmolar syndrome in type II diabetes

Answer 27

high concentrations of glucose and electrolytes in blood cause water to move from tissues into blood, causing dehydration of tissues and brain

Question 28

can diet and exercise reduce HbA1c levels

Answer 28

YES

Question 29

HbA1c

Answer 29

-glucose forms a covalent bond with Hb (glycates Hb) when it is found in high concentrations
-higher glucose levels cause more adduction and elevated HbA1c

Question 30

advanced glycation end products (AGE)

Answer 30

1) glucose converted to a reactive derivative
2) it reacts spontaneously with cellular proteins and forms covalent complexes
3) the protein is altered such that they bind and form cross-linked structures (ECM is especially vulnerable)
*lowers the elasticity of blood vessel walls and impedes normal blood flow

Question 31

advanced glycation end products (AGE) and kidney

Answer 31

glycation of the glomerulus prevents the filtration system from working, which can lead to kidney failure
*problematic for diabetes patients due to excess glucose in circulation

Question 32

how does metformin help diabetes

Answer 32

suppresses transcription of gluconeogenesis enzymes (PEP-carboxykinase and glucose-6-phosphatase) and reduces hepatic glucose output