Glucose 1

Question 1

What are the different glucose transporters, where are they located, and which ones require insulin to work?

Answer 1

• GLUT1&3 = brain
• GLUT2 = liver and pancreatic B-cells
• GLUT4 = muscle and adipocytes (insulin required)

Question 2

This is the only glucose transporter that requires insulin to work.

Answer 2

GLUT4 (muscle and adipocytes)

Question 3

What is the mode of inheritance for ALL glycogen storage disorders?

Answer 3

AR

Question 4

Summary GSD 0.

Answer 4

• Genetics: AR mutation in GYS2 (glycogen synthase) (can’t make glycogen)
• Phenotype: NO hepatomegaly since you can’t make glycogen.
• Labs: Fasting hypoglycemia + PP HYPERglycemia

Question 5

Which glycogen storage disease causes post-prandial hyperglycemia?

Answer 5

GSD 0

Question 6

Summarize glycogen storage disorder 1.

Answer 6

• AKA Von Gerke’s
• Genetics: AR mutation in G6Phosphatase (can’t break down glycogen).
• Phenotype: Hepatomegaly since you can’t break down glycogen.
• Labs: Hypoglycemia with LLUAN – elevated Lactate, hyperLipidemia, hyperUricemia, Anemia, Neutropenia in 1b.

Question 7

Summarize glycogen storage disease 2.

Answer 7

• AKA Pompe
• Genetics: AR mutation in acid-alpha-glucosidase (GAA = think of 2 A’s from the name GSD 2) (can’t release glycogen from lysosomes)
• Phenotype: Hepatomegaly since can’t release glycogen and heart failure
• Labs: Hypoglycemia

Question 8

Summarize glycogen storage disorder 3.

Answer 8

• AKA Cori’s
• Genetics: AR mutation in the debranching enzyme (can’t break down glycogen) –> think of Cori from clinic wearing a Hawaiian shirt with lots of branches on it.
• Phenotype: Hepatomegaly since can’t break down glycogen
• Labs: Hypoglycemia

Question 9

What is the treatment for glycogen storage disorders?

Answer 9

cornstarch

Question 10

What is the mode of inheritance for fatty acid oxidation disorders?

Answer 10

AR

Question 11

Summarize MCADD.

Answer 11

• Medium chain acylcarnitine deficiency
• Genetics: AR mutation in ACADM on chromosome 1.
• Phenotype: normal
• Labs = medium chain = elevated C6-10. fasting HYPOketotic hypoglycemia

Question 12

Summarize VLCADD.

Answer 12

• Very long chain acylcarnitine deficiency.
• Genetics: AR mutation in ACADVL
• Phenotype: cardiomyopathy
• Labs = long chain = elevated C12-14

Question 13

Summarize carnitine transporter deficiency.

Answer 13

• Genetics: AR mutation in SLC22A5
• Phenotype: Normal.
• Labs: RTA, low total and free carnitine levels due to renal wasting of carnitine.

Question 14

Summarize CPT1A deficiency.

Answer 14

• Genetics: AR mutation in CPT1A
• Phenotype: Fatty liver w/ risk hepatic encephalopathy
• Labs: High total and free carnitine, low acylcarnitine, low C16, low C18

Question 15

What is the treatment for fatty acid oxidation disorders?

Answer 15

1. frequent high carb, low fat meals
2. cornstarch

Question 16

Why does alcohol lead to hypoglycemia, particularly with insulin on board?

Answer 16

• In order to metabolize alcohol, the liver uses up all the NAD+ and pushes it into NADH.
• NADH builds up and inhibits the TCA cycle, which is necessary for gluconeogenesis.

Question 17

How long should people be able to fast according to age?

Answer 17

• Infancy: 18h
• 1yo: 24h
• 5yo: 36h
• Adults: 2-3d

Question 18

Summarize the counterregulatory responses of insulin and glucagon.

Answer 18

“Gloria Gets Fat, Keeps Producing Sugar”. Insulin:
- Inhibits gluconeogenesis
- Inhibits glycogenolysis
- Inhibits fat lipolysis
- Inhibits ketogenesis
- Stimulates protein synthesis

Glucagon does the exact opposite EXCEPT it has no effect on fat lipolysis.

Question 19

Summarize the counterregulatory responses of cortisol.

Answer 19

“Gloria Gets Fat, Keeps Producing Sugar”. Think of a person with Cushing’s. CortisoL:
- Stimulates gluconeogenesis (makes you fat)
- Stimulates proteolysis (think of the skinny arms/legs in someone w/ Cushing’s).

Question 20

Summarize the counterregulatory responses of growth hormone.

Answer 20

“Gloria Gets Fat, Keeps Producing Sugar”. Growth hormone:
- Stimulates gluconeogenesis.
- Stimulate glycogenolysis.
- Stimulates fat lipolysis yet also downregulates LPL.
- Stimulates ketogenesis.
- Stimulates protein synthesis.

Question 21

What is the dawn effect?

Answer 21

• Growth hormone levels increase during puberty.
• Since growth hormone also decreases glucose uptake in muscles and fat, you get physiologic hyperglycemia of puberty in the early morning hours.

Question 22

Summarize the counterregulatory responses of epinephrine.

Answer 22

“Gloria Gets Fat, Keeps Producing Sugar”. Epi:
- Stimulates gluconeogenesis.
- Stimulate glycogenolysis.
- Stimulates fat lipolysis.
- Stimulates ketogenesis.
- Doesn’t have much effect on protein synthesis.

Question 23

Where in the body does insulin cause glucose uptake?

Answer 23

MAL
- Muscle
- Adipose
- Liver

Question 24

What is the half-life of insulin? Where is it cleared in the body?

Answer 24

• 4 mins
• 50% cleared in liver
• 30% cleared in kidney
• 20% in periphery

Question 25

What is the ratio of C-peptide to insulin within insulin secretory granules? Which is a more reliable assay and why?

Answer 25

- 1:1 - Because C-peptide has a longer half-life than insulin, it is a more reliable assay.

Question 26

Summarize B-cell physiology and secretion of insulin.

Answer 26

Insulin --> goes into B-cells via GLUT2 (or GLUT1?) --> glucose gets phosphorylated via GCK --> glucose gets metabolized in the mitochondira via TCA to make ATP --> buildup of ATP causes CLOSURE of Kir (inward rectifying potassium channel) --> K+ accumulates inside B-cells --> cell depolarizes from all the K+ --> calcium channels open ----> influx of calcium --> degranulation of insulin vesicles --> release of insulin.

Question 27

What is the natural state of the pancreatic B-cell K+ channels with regards to polarization?

Answer 27

K+ cells are usually OPEN due to hyperpolarization

Question 28

How do you remember whether the K+ channel is open or closed with regards to insulin release in the pancreatic B-cells?

Answer 28

"When the gate is closed, insulin flows" via depolarization.

Question 29

**What is Kir?**

Answer 29

- Inward rectifying potassium channel on B-cells. - It's made of TWO components: KIR6.2 (inner domain from KCNJ11 gene on 11p15) and SUR1/sulfonylurea 1 (outer domain from ABCC8 gene on 11p15).

Question 30

How do sulfonylureas like glipizide and glyburide work?

Answer 30

They stimulate outer receptor on the K+ potassium channel of pancreatic B-cells (called SUR1 and made from ABCC8 gene on 11p15) to close --> membrane depolarizes --> release of insulin.

Question 31

Why does maternal hyperglycemia cause fetal growth?

Answer 31

maternal hyperglycemia --> fetal insulin secretion --> increased fetal growth

Question 32

Why does maternal hyperglycemia cause fetal hypocalcemia?

Answer 32

Hyperglycemia for some reason causes delay in parathyroid gland transition.

Question 33

How do you calculate GIR?

Answer 33

GIR = [IV rate (cc/h) x dex concentration (# not decimal) x 0.167]/weight (kg)

Question 34

When should you screen for T2D?

Answer 34

- Elevated wt (85th%+) and 10yo+ PLUS at least 1 risk factor - Maternal diab or GDM - T2D in first or second-degree fam members - Patient of color - E/o insulin resistance, including common comorbidities and being born SGA - If tests normal, repeat in 2-year intervals unless BMI going up

Question 35

Why does L-asparaginase cause diabetes mellitus?

Answer 35

1. Decreased insulin synthesis 2. Damage to the insulin receptor 3. High glucagon levels

Question 36

What is Whipple's triad?

Answer 36

1. Sxs c/w hypoglycemia. 2. Documented low BGs. 3. Improvement in sxs once BG comes up.

Question 37

What are examples of calcineurin inhibitors? Why do they cause diabetes?

Answer 37

- Examples: Tacrolimus and cyclosporine. - They cause decreased insulin secretion, thus leading to diabetes.

Question 38

What are some examples of immune checkpoint inhibitors? How do they influence blood sugars?

Answer 38

- Examples: Most end in -umab (example is Nivolumab. - They cause destruction of pancreatic B cells from cytotoxic T-cells thus leading to diabetes mellitus.

Question 39

What do the alpha and delta cells of the pancreas secrete?

Answer 39

- Alpha cells secrete glucAgon. - Delta cells secrete somatostatin.

Question 40

**What is the timing of hormones in the counterregulatory response to hypoglycemia?**

Answer 40

GEG-C Glucagon > Epi > GH > cortisol

Question 41

What targets organs does GH act on?

Answer 41

Like insulin, acts on MAL (Muscle, Adipose, Liver)

Question 42

What triggers the release of glucagon?

Answer 42

hypoglycemia + protein ingestion

Question 43

**Which GSDs cause muscle cramping and weakness?**

Answer 43

GSDs 0,2,3

Question 44

What is fructose 1,6-bisphosphatase deficiency?

Answer 44

- Genetics: AR mutation in FBP1 (can't break down glycogen) - Phenotype: Hypoglycemia. - Labs: Lactic acidosis.

Question 45

What is Fanconi Bickel syndrome?

Answer 45

- Genetics: AR mutation in SLC2A2 on chromosome 3, which makes the GLUT2 receptors (help glucose go into liver and pancreatic B-cells). As a result, glucose accumulates in liver and kidneys. - Phenotype: Hepatomegaly + nephropathy. - Labs: Hypoglycemia.

Question 46

What is the normal BG range that glucokinase (GCK) uses to turn on and lead to downstream release of insulin?

Answer 46

70-100 mg/dL