Lecture 58

Question 1

What are catabolic factors (hormones) that increase plasma glucose levels?

Answer 1

1) Glucagon
2) Epinephrine
3) Cortisol
4) Growth hormone

Question 2

What are anabolic factors (hormones) that reduce plasma glucose levels?

Answer 2

Insulin

Question 3

As blood glucose levels decrease, list the order of factors that occur in the body to try maintain blood glucose levels

Answer 3

1) Insulin production decreases (above 80 mg/dL)
2) Epinephrine and glucagon production increases (60-70 mg/dL)
3) Growth hormone production increases (60-70 mg/dL)
4) Cortisol production increases (60-70 mg/dL)
5) Adrenergic symptoms begin (anxiety, palpitation, tremor, sweating) (Just below 60 mg/dL)
6) Neuroglycopenia symptoms begin (headache, confusion, slurred speech, seizures, coma, & death) (50 mg/dL or below)

Question 4

What blood glucose levels are indicative of diabetes?

Answer 4

1) Fasting blood glucose levels =>126mg/dL

2) Random blood glucose levels =>200 mg/dL

Question 5

What is a key concept between the ratio of insulin & glucagon?

Answer 5

Ratios of insulin & other hormones, particularly glucagon, regulate tissue specific metabolism under different nutritional states (e.g., fed, fasting, & prolonged starvation)

Question 6

What must excess glucose, amino acids, & triglycerides be converted to?

Answer 6

Glycogen, fat, & protein

Question 7

What part of the body produces insulin in the presence of excess glucose & amino acids?

Answer 7

Insulin is produced by beta cells in the islets of Langerhans in the pancreas

Question 8

How low must your blood glucose levels be they begin producing catabolic factors such as glucagon, epinephrine, cortisol, & growth hormone?

Answer 8

Below 18mg/dL or 1mmol/L

Question 9

How high must your blood glucose levels be they begin producing the anabolic factor insulin?

Answer 9

Above 162 mg/dL or 9 mmol/L

Question 10

What occurs in an insulin-activated liver?

Answer 10

1) GLUT2 transporters transport glucose from the gut into the liver
2) High Km (low affinity) glucokinase glycolysis
3) Increased Glycogen synthesis
4) Increased Pentose phosphate pathway
5) Increased Protein synthesis
6) Increased Fatty acid and TAG synthesis

Question 11

What occurs in an insulin-repressed liver?

Answer 11

1) Decreased gluconeogenesis (inactive pyruvate carboxylase & fructose 1,6-bisphosphatase)
2) Decreased glycogen breakdown (inactive glycogen phosphorylase)
3) Decreased fat breakdown

Question 12

What occurs in activated pathways in resting skeletal muscle?

Answer 12

1) GLUT4 transporter transports glucose into the muscle
2) Increased glycolysis
3) Increased glycogen synthesis
4) Increased protein synthesis

Question 13

What occurs in repressed pathways in resting skeletal muscle?

Answer 13

1) Decreased glycogen breakdown

Question 14

What occurs in activated pathways in adipose tissue?

Answer 14

1) GLUT4 transporter brings glucose into adipocytes
2) Increased glycolysis (PFK, pyruvate DH)
3) Increased Pentose phosphate pathway
4) Most fat stored from diet in the form of triacylglycerol

Question 15

What occurs in repressed pathways in adipose tissue?

Answer 15

1) Decreased glycogen breakdown

Question 16

How does the brain produce energy?

Answer 16

1) When the brain receives glucose, it uses only glucose

2) Brain completely oxidizes glucose to CO2 & H2O

Question 17

Describe what occurs after excess caloric intake

Answer 17

1) Dietary carbohydrate and dietary protein can be converted to body fat: When caloric intake exceeds energy expenditure, dietary carbohydrate and protein can be converted to tracylglycerol in the liver for ultimate deposition in the adipose tissue
2) Dietary fat can be converted to body fat: When caloric intake exceeds energy expenditure, dietary fat can be converted to triacylglycerol in the adipose tissue
3) Insulin is an anabolic signal that promotes synthesis of glycogen, protein, & triacylglycerol

Question 18

What is the basic concept of how a hormone receptor is structured and functions?

Answer 18

1) Exquisitely selective extracellular domain, aka ligand binding domain (LBD)
2) Hydrophobic transmembrane domain anchors receptor in membrane and couples LBD to intracellular domain
3) Cytoplasmic/intracellular domain is the effector domain

Question 19

What occurs when a Receptor Tyrosine Kinase (RTK) is activated by a molecule such as insulin?

Answer 19

1) Insulin (in the form of a dimer) activates a Receptor Tyrosine Kinase (RTK) on responding cells
2) Tyrosine residues on the receptor become phosphorylated very rapidly
3) The enzyme and substrate are both part of the receptor (intrinsic activity)
4) Intracellular signaling proteins can now bind to the phosphorylated tyrosines and relay the signal

Question 20

What are roles of Receptor tyrosine kinases (RTK)?

Answer 20

1) Carbohydrate utilization and protein synthesis (e.g. insulin)
2) Regulation of cell growth & survival (e.g. EGF, IGFs)
3) Angiogenesis (e.g. Vascular endothelial growth factor, VEGF)

Question 21

How do the adaptor proteins bound to the phosphorylated tyrosine receptor relay the signal?

Answer 21

1) Adapter proteins activate Monomeric G Proteins (e.g. Ras) that activate kinases
2) Kinases that are activated include Kinase 1 (MAPKKK (RAF)), Kinase 2 (MAPKK (MEK)), & Kinase 3 (MAPK (ERK))
3) There are then changes in protein activity & gene expression

Question 22

Other than RTK, what are other important hormone receptors with intrinsic enzyme activity?

Answer 22

1) TGF Beta receptors – serine kinases, e.g. activin, inhibin, transforming growth factor (TGF) beta, bone morphogenetic proteins (BMPs)
2) Receptor guanylyl cyclases generate the 2nd messenger cGMP, e.g. atrial natriuretic factor (ANF) & related peptide hormones
3) Again, intrinsic means the enzyme is part of the receptor protein

Question 23

What is occurring in the liver when someone is hungry?

Answer 23

1) Increased glycogen breakdown
2) Increased gluconeogenesis
3) Increased Fatty acid oxidation
4) Increased ketone body synthesis

Question 24

What occurs in an adipocyte when someone is hungry?

Answer 24

1) Increased triacylglycerol degradation
2) Increased fatty acid & glycerol release
3) Decreased fatty acid uptake

Question 25

What occurs in muscles when someone is hungry?

Answer 25

1) Fuel switches from glucose to FAs & KBs

2) Protein breakdown provides AAs for liver GNG

Question 26

What happens in the brain when someone is hungry?

Answer 26

1) Initially, glucose from the liver is formed from gluconeogenesis
2) After 2-3 weeks, uses ketone bodies

Question 27

What are the two priorities during hunger?

Answer 27

1) Blood glucose is maintained first by degradation of liver glycogen, followed by hepatic gluconeogenesis (feed the glucose-requiring tissues)
2) Mobilization of triacylglycerols from adipose provides fatty acids & precursors for ketone bodies (feed the nonglucose-requiring tissues)

Question 28

How much glucose is produced by gluconeogenesis in the kidney during an overnight fast as compared to in starvation?

Answer 28

1) 10% in overnight fast

2) 40% in starvation

Question 29

Contrast starvation & Diabetes Mellitus (DM):

Answer 29

Starvation:
1) Slightly lowered glucose levels
2) Increased fatty acid oxidation, increased formation of ketone bodies, decreased protein synthesis in muscle and increased gluconeogenesis in liver
3) Low insulin levels
4) Increased hunger
Diabetes mellitus:
1) High glucose levels
2) Increased fatty acid oxidation, increased formation of ketone bodies, decreased protein synthesis in muscle & increased gluconeogenesis in liver
3) Absent or normal/high insulin levels depending on type
4) Increased hunger, frequent urination, and increased thirst, (polyphagia, polyuria, & polydipsia)

Question 30

What occurs in Type 1 diabetes?

Answer 30

1) Absolute deficiency of insulin
2) Autoimmune destruction of beta cells
3) Hyperglycemia
4) Ketoacidosis

Question 31

What occurs in Type 2 diabetes?

Answer 31

1) Decreased response to insulin
2) Hyperglycemia
3) Less glycogenesis
4) More gluconeogenesis
5) Less muscle & fat glucose uptake
6) Residual insulin restrains
7) Ketogenesis

Question 32

What can increase your risk of developing diabetes type 2?

Answer 32

Metabolic syndrome (not really used clinically anymore):

1) Central or abdominal obesity
2) High fasting blood triglycerides
3) Lower blood HDL cholesterol
4) High blood pressure
5) High, but not diabetic, fasting glucose

Question 33

What are types of defects that can cause genetic diabetes to arise (maturity onset diabetes of the young (MODY)?

Answer 33

1) Transcription factors that control expression of metabolism genes
2) Metabolic enzymes
3) Signaling defects

Question 34

What is the function of Metformin?

Answer 34

1) Metformin activates AMP-Activated Protein Kinase (AMPK)
2) This promotes: Glycolysis in the liver & glucose uptake in muscle
3) This inhibits: Fatty acid synthesis & gluconeogenesis

Question 35

What can be said about hemoglobin A1c in relation to glucose?

Answer 35

1) Hemoglobin A1c are normally 4-6% of total HbA1c
2) Hemoglobin A1c can be glycosylated by free glucose
3) Because this reaction is irreversible, blood HbA1c is not cleared until an erythrocyte is replaced

Question 36

Compare and contrast diabetes 1 and 2

Answer 36

Diabetes 1:

1) Usualy childhood or puberty, rapid onset of symptoms
2) Normal weight to wastd
3) ~10% of diagnoses
4) moderate genetic predisposition
5) Beta cells destroyed, no insulin produced
6) Ketosis common
7) Acute complication: Ketoacidosis
8) Treatment: insulin replacement

Diabetes 2:

1) Often after age 35, gradual onset of symptoms
2) Associated with obesity
3) ~90% of diagnoses
4) very strong genetic predisposition
5) Insulin resistance with abnormal insulin levels (low, normal, high)
6) Ketosis is rare
7) Acute complication: Hyperosmolar coma
8) Treatment: Diet, exercise, oral hypoglycemic drugs, possibly insulin

Question 37

What directly inhibits glucose production within the liver cell?

Answer 37

Alcohol