Metabolic Homeostatis

Question 1

What occurs with starvation?

Answer 1

• Proinflammatory cytokines
• Activation of HPA axis
• Dysregulation of growth hormone and IGF-I

Question 2

What is the initial energy source for the brain?

Answer 2

Glucose.

80% from fat stores, release of FFAs, breakdown of liver glycogen, breakdown of proteins

Question 3

What is the energy for the brain in a prolonged fast?

Answer 3

Ketone bodies used as energy source for brain with reduced reliance on glucose as fuel source

Question 4

What is syndrome X?

Answer 4

It is a metabolic syndrome often combined with obesity and diabetes.

Question 5

What are the four factors of syndrome X?

Answer 5

• Visceral Obesity
• Insulin Resistance
• Dyslipidemia – TGs > 150 mg/dl, HDL
• Hypertension

Question 6

What is the primary hormone produced by adipose tissue?

Answer 6

Leptin

Question 7

What is the function of Sterol regulatory binding protein 1C (SREBP-1C)?

Answer 7

Promotes TAG synthesis
Activated by lipids and insulin
Increases glucokinase “trapping” glucose inside cells.

Question 8

What is the function of PPARgamma?

Answer 8

Nuclear steroid hormone receptor

Regulates TG storage and adipocyte differentiation

Question 9

What is the function of PPARgamma agonists?

Answer 9

PPARγ agonists used to treat insulin resistance and Type 2 diabetes mellitus

Question 10

What is the side effect of PPARgamma agonists?

Answer 10

Weight gain

Question 11

What is the relationship between leptin and total fat?

Answer 11

Direct

Question 12

What is insulin resistance?

Answer 12

Insulin does not efficiently transport glucose into cells -> due to constant high glucose levels and high insulin levels

Question 13

What can beta cell exhaustion cause in diabetes patients?

Answer 13

Conversion from Type II to Type I

Question 14

What is the main diagnosis factor for diabetes type II?

Answer 14

Elevated HbA1C - shows the glycosylation of RBCs which is over a longer period of time

Question 15

What are the main symptoms of diabetes mellitus type II?

Answer 15

Polyphagia
Polyuria
Polydipsia

Question 16

What is the mechanism of sulfonylureas in treating DM Type II?

Answer 16

Close ATP-dependent K+ channels in beta cells causing insulin release

Question 17

What is the function of biguanides like metformin in treating DM Type II?

Answer 17

Inhibits hepatic gluconeogenesis

Increases insulin receptor activity making cells more sensitive to insulin, increased glucose uptake

Question 18

What is the cause of DM Type I?

Answer 18

Destruction of pancreatic beta cells – causes insulin dependence

Question 19

What is found in untreated DM Type I?

Answer 19

Ketoacidosis

Question 20

How does diabetic ketoacidosis occur?

Answer 20

Decreased insulin ->
Increased counter regulatory hormones ->
Increased FFA release – hepatic precursor for ketone acids ->
Ketone metabolism ->
Increases blood [H+] ->
Prolonged increased acidity will lead to ketoacidosis and then coma

Question 21

Does ketogenesis occur in absolute insulin deficiency, like Type I DM?

Answer 21

Yes

Question 22

Does ketogenesis occur in relative insulin deficiency, like Type II DM?

Answer 22

No

Question 23

Describe insulin and GH function in the fed state.

Answer 23

The presence of insulin with a mixed meal will lead to GH release which will stimulate IGF-I which will increase glucose uptake in muscle and inhibits proteolysis.

GH opposes lipgenesis of insulin

Question 24

Describe insulin and GH function in the starvation state.

Answer 24

No insulin with low glucose and glucagon is stimulated as insulin is not there to inhibit it. GH will increase due to AAs from increased proteolysis.

No IGF-I with no insulin so there is no negative feedback on GH.

Question 25

Describe insulin and GH function in DM Type I.

Answer 25

No insulin but there is HIGH glucose since the patient is eating. Glucagon is stimulated without inhibition though with no insulin.

GH will be increased with increased proteolysis with no negative feedback due to no IGF-I.

Question 26

Describe insulin and GH function in DM Type II.

Answer 26

Low insulin or insulin is not receipted.

HIGH glucose with glucagon stimulated but it is inhibited since insulin is present. Presence of insulin also inhibits ketogenesis.

Question 27

What are the risk factors for Type II DM?

Answer 27

Genetic predisposition

Impaired beta cell proliferation during childhood

Increased propensity for insulin resistance

• High caloric diet
• Lack of physical activity

Question 28

When does islet cell development begin and end?

Answer 28

Islet neogenesis occurs during embryonic development and beta cell replication continues during childhood/adolescence but is stable in adults

Question 29

What gene is important for both islet neogenesis and beta cell proliferation?

Answer 29

PDX-1

Question 30

What gene targets regulate beta cell proliferation?

Answer 30

TCF72

Question 31

What is the first change in insulin release found in DM Type II?

Answer 31

On the biphasic graph of insulin release, the first spike will be much smaller compared to normal people.

Question 32

What happens to the beta cells and insulin secretion in the early phases of Type II DM?

Answer 32

Insulin secretion and beta cell mass will be markedly increased.

Question 33

What happens to the beta cells and insulin secretion in late phases of Type II DM?

Answer 33

Insulin secretion and beta cell mass will show a marked decline compared to normal.