(5) GI & Endo: DM (2.1-2.2)

Question 1

Stimulation of what adrenergic receptor increases insulin secretion?

Answer 1

β₂

Question 2

How does glucose induce insulin release?

Answer 2

Closes ATP dependent K+ channels

↑ Glucose

⇒ ↑ Aerobic respiration

⇒ ↑ ATP

⇒ Closure of ATP gated K+ efflux channels

⇒ ↑ Membrane voltage

⇒ Opening of voltage gated Ca2+ channels

⇒ Ca2+ influx

⇒ Exocytosis of insulin

Question 3

Name 2 proteins secreted from the same vesicle as insulin

Answer 3

(1) C-peptide
(2) Amylin
* (Note: C-peptide is not included in exogenous insulin ∴ C-peptide can be used as a marker for insulin poisoning)*

Question 4

What class of receptor is the insulin receptor?

Answer 4

Intrinsic receptor tyrosine kinase

Question 5

What receptor does insulin upregulate in peripheral tissue?

Answer 5

GLUT4

Question 6

What metabolic changes occur after insulin binds its receptor?

Answer 6

(1) ↑ Glycogen
(2) ↑ Anabolism
(3) ↑ TG synthesis

Question 7

How does insulin decrease serum K⁺ levels?

Answer 7

↑ Activity of Na+/K+ ATPase

(Predominantly in skeletal muscle)

Question 8

What are the rapid-acting, short-duration insulin analogs?

Answer 8

(1) insulin Glulisine
(2) insulin Aspart
(3) insulin Lispro

Question 9

What insulin analogs are used for control of postprandial glucose spike?

Answer 9

(1) insulin Glulisine
(2) insulin Aspart
(3) insulin Lispro

Question 10

What are the intermediate-acting insulin analogs?

Answer 10

(1) Regular insulin
(2) NPH insulin

Question 11

What is the only insulin analog available for IV administration?

Answer 11

Regular insulin

Question 12

Treatment: Diabetic ketoacidosis

Answer 12

IV regular insulin

(Remember to add K+ to avoid hypokalemia)

Question 13

What hormone can be used to treat hyperkalemia?

Answer 13

Insulin

(Remember to add glucose to avoid hypoglycemia)

Question 14

What are the long-acting insulin analogs?

Answer 14

(1) insulin Detemir
(2) insulin Glargine
* (G-_LARGE_-ine is the longest acting insulin analog)*

Question 15

What is the most common complication of insulin therapy?

Answer 15

Hypoglycemia

(Duh!)

Question 16

MOA: Sulfonylureas

Answer 16

Inhibit ATP-dependent K+ channels

• (↑ Endogenous insulin ∴ ↑ C-peptide)*
• (↑ Endogenous insulin ∴ Only treats T2DM)*

Question 17

Suffix: First-generation sulfonylureas

Answer 17

“-amide”

Question 18

Suffix: Second-generation sulfonylureas

Answer 18

“-ride”

Question 19

What second-generation sulfonylurea has the shortest duration of action?

Answer 19

Glipizide

Question 20

Indication: Meglitinides

Answer 20

T2DM

Question 21

Other than hypoglycemia, what is a common side effect of sulfonylureas and meglitinides?

Answer 21

Weight gain

Question 22

What class of diabetes drugs can cause a disulfiram-like reaction?

Answer 22

First-generation sulfonylureas

Question 23

Suffix: GLP-1 analogs

Answer 23

“-tide”

Question 24

What are the physiologic actions of GLP-1?

Answer 24

(1) ↓ Glucagon secretion
(2) Delay gastric emptying
* (Satiety, ↓ Glucagon release, Inhibit gastric emptying)*

Question 25

**MOA**: "-gliptin" drugs

Answer 25

Inhibit DDP-4 *(And ∴ degradation of GLP-1. Gliptins be GLP-liftin)*

Question 26

What class of drugs increases levels of endogenously secreted GLP-1?

Answer 26

Gliptins *(Gliptin = GLP-Liftin')*

Question 27

**Adverse Effects** (2) : DPP-4 inhibitors

Answer 27

(1) Nasopharyngitis (2) URTIs

Question 28

Which diabetes drugs do not cause hypoglycemia?

Answer 28

(1) GLP-1 analogs (2) DDP-4 inhibitors * (∵ Effects are glucose-dependent, diminishing as glucose levels approach normal)*

Question 29

Can GLP-1 agonists treat T1DM?

Answer 29

No

Question 30

**Adverse Effect**: GLP-1 inhibitors

Answer 30

Pancreatitis

Question 31

Name an enzyme that Metformin inhibits and one that it activates

Answer 31

(1) _Inhibits_: mGPD (2) **_Activates_**: AMP Kinase * (mGPD = Inhibits mitochondrial enzyme glycerophosphate dehydrogenase)* * (AMPK ↓ Gluconeogenesis and ↑ Insulin sensitivity)*

Question 32

Other than affecting gluconeogenesis, what is the mechanism of Metformin?

Answer 32

↑ Insulin sensitivity *(Other aspects include ↓ intestinal absorption of glucose)*

Question 33

**Adverse Effects** (2) : Metformin

Answer 33

(1) Lactic acidosis (2) GI Issues

Question 34

How is Metformin excreted?

Answer 34

Renal *(Unaltered and in active form)*

Question 35

Name a diabetes drug which may cause weight loss

Answer 35

Metformin

Question 36

**Suffix**: Thiazolidinediones

Answer 36

"-glitazone"

Question 37

**MOA**: Glitazones

Answer 37

PPAR-**γ** ligand *(∴ ↑ Insulin sensitivity and fatty acid oxidation)*

Question 38

How do glitazones ↓ serum triglyceride levels?

Answer 38

(1) ↑ Fatty acid oxidation (2) ↑ Differentiation of adipocytes

Question 39

Name 2 proteins that glitazones upregulate

Answer 39

(1) Adiponectin (2) GLUT4

Question 40

**Adverse Effects** (4) : Glitazones

Answer 40

(1) Weight gain (2) Peripheral edema (3) ⇒ Heart failure (4) ↓ Bone mineral density

Question 41

What are the physiologic effects of Amylin?

Answer 41

(1) ↓ Gastric emptying (2) ↓ Glucagon

Question 42

What drug can be used to treat T1DM and T2DM but is not an insulin analog?

Answer 42

Amylin

Question 43

**Adverse Effects** (2) : Amylin

Answer 43

(1) Hypoglycemia (2) GI upset

Question 44

Name 2 α-glucosidase inhibitors

Answer 44

(1) Acarbose (2) Miglitol

Question 45

What is the mechanism of α-glucosidase inhibitors in treating diabetes?

Answer 45

↓ Intestinal glucose absorption

Question 46

Why are α-glucosidase inhibitors infrequently prescribed?

Answer 46

Severe abdominal side effects *(Undigested GI sugars ∝ Symptoms of lactose intolerance)*

Question 47

**Suffix**: SGLT2 inhibitors

Answer 47

"-flozin"

Question 48

**MOA**: "-flozin" drugs

Answer 48

Inhibit SGLT2 *(In proximal convoluted tubule ∵ that's where everything is reabsorbed)*

Question 49

**Adverse Effects** (3) : SGLT2 inhibitors

Answer 49

(1) ↑ Frequency of urination (2) UTIs (3) ↑ Risk of vaginal candidiasis (↑ Urination ⇒ Hypotension)

Question 50

**Contraindication**: SGLT2 inhibitors

Answer 50

Renal sufficiency