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D1 Spring > Pharmacology - Insulin, Oral Hypoglycemic Agents, Glucagon (Exam 5) > Flashcards

Pharmacology - Insulin, Oral Hypoglycemic Agents, Glucagon (Exam 5) Flashcards

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1
Q

The principal hormone that’s dysregulated in diabetes

A

Insulin

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2
Q

What is signaled by the presence of usable energy and tells the body to store energy?

A

Insulin release

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3
Q

What is the structure of proinsulin?

A

A chain
B chain
C chain

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4
Q

Through the proteolytic cleavage of proinsulin, which chain gets cleaved?

A

C chain

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5
Q

T/F the C chain has no known physiological function

A

True

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6
Q

What is the active part of insulin?

A

A and B chain

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7
Q

What are A and B chains of proinsulin linked by?

A

Disulfide bonds

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8
Q

How do you inactivate insulin?

A

Hydrolyze the disulfide bond between A and B chain

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9
Q

Why do we care about the structure of insulin?

A

All therapies for type I diabetes are mimetics of insulin and have a similar structure

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10
Q

How fast is insulin’s half life?

A

3-5 mins

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11
Q

Where is endogenous insulin metabolized vs subcutaneously introduced insulin metabolized?

A

Endogenous: 60% liver, 40% kidney
Subcutaneous: 60% kidney, 40% liver

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12
Q

How much insulin does the pancreas hold?

A

8 mg (~200 units)

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13
Q

Which cells in the pancreas secrete insulin?

A

B cells

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14
Q

Name some secretory products of B cells

A

Insulin
C chain (peptide)
Proinsulin
Islet amyloid polypeptide (IAPP)

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15
Q

Which cells in the pancreas make glucagon?

A

A cells

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16
Q

T/F: The pancreas is mostly made up of alpha cells.

A

False! It’s mostly beta cells

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17
Q

Insulin secretion steps (7) (ON EXAM)

A
  1. High levels of glucose
  2. Glucose enters cell via GLUT2 and gets metabolized
  3. ATP is produced
  4. ATP phosphorylates and closes K+ channels
  5. Beta cell gets depolarized
  6. Voltage gated Ca2+ channels open
  7. Increased Ca2+ leads to the release of insulin
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18
Q

Most important step of insulin secretion

(this is what drugs that increase insulin secretion target)

A

When ATP closes the K+ channels and causes depolarization of the Beta cell

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19
Q

Insulin released from beta cells is a complex of what?

A

6 insulin molecules with 1 Zn atom

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20
Q

T/F when insulin is in a complex with Zinc, it cannot find its target receptor and it is NOT biologically active

A

True

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21
Q

Only the ___________ form of insulin is able to bind to the receptor

A

monomeric

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22
Q

3 insulin responsive tissues (ON EXAM)

A
  1. Liver
  2. Muscle
  3. Adipose
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23
Q

Insulin receptors have ___________ _________ activity

A

intrinsic enzymatic

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24
Q

Steps of insulin receptor signal transduction (ON EXAM)

A
  1. Insulin binds to insulin receptor
  2. IRS proteins are stimulated
  3. Glucose transporters (GLUT-4) move from intracellular vesicles to plasma membrane
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25
Where is GLUT-2 transporter always located?
Plasma membrane
26
Where is GLUT-4 transporter located?
Translocates to the plasma membrane when activated by insulin receptor
27
Elevated levels of glucose leads to the release of ________ which leads to _________ _________
insulin; energy storage
28
Decreased levels of glucose leads to decreased levels of _________, which leads to the body using ________ ______ to make more ________
insulin; stored energy; glucose
29
Blood glucose levels serve as a ____________ for insulin action
surrogate
30
What are the physiologically most important roles of insulin? (ON EXAM)
1. Increased glycogen synthesis 2. Glucose uptake (removal from the blood)
31
The improper synthesis or use of insulin characterized by hyperglycemia
Diabetes
32
Diabetes differences in ethnic groups are because of?
Socioeconomic status (NOT genetics)
33
Common oral health problems associated w/ diabetes (7)
1. Tooth Decay 2. Periodontal disease 3. Salivary gland dysfunction 4. Fungal Infection 5. Lichen planus and lichenoid reactions 6. Infection and delayed healing 7. Taste impairment
34
What are the major classifications of diabetes?
Type I, II, III, and IV
35
Which type of diabetes? Insulin dependent diabetes mellitus
Type I
36
Which type of diabetes? Non-insulin dependent diabetes mellitus
Type II
37
Which type of diabetes? Diabetes linked to pancreatic disease, hormonal changes, drug side effects, or genetic defects
Type III
38
Which type of diabetes? Gestational diabetes
Type IV
39
Difference in treatment betweeen Type I and Type II diabetes
Type I: do NOT have functioning B cells; patient provides their own insulin (replacement therapy) Type II: less responsive to insulin; must secrete more insulin, reduce blood glucose from diet, or restore sensitivity to insulin
40
Goals of Type I diabetes
1. Stabilize glucose concentrations in blood 2. Mediate all of insulins's functions
41
What are the advantages of glycemic control in Type I diabetes?
1. Decrease swings in glucose levels 2. Decrease glycated Hgb 3. Decrease eye, kidney, nerve damage
42
What are the disadvantages of glycemic control in Type I diabetes?
1. Hypoglycemia risk 2. Weight gain
43
Differences between insulin preparations for treatment of Type I diabetes are __________
pharmacokinetic (onset and duration of action is different for each one)
44
What are the insulin delivery systems?
1. Subcutaneous injection (needles/syringes, portable pen injectors) 2. Continuous subcutaneous insulin infusion devices (insulin pump)
45
What is the main problem in Type II diabetes?
Decreased insulin sensitivity
46
Type II diabetes drugs have 3 therapeutic goals. What are they?
1. Insulin release 2. Increase insulin sensitivity 3. Decrease blood glucose
47
Name 2 insulin secretagogues. Which goal do they target?
1. Sulfonylureas 2. Meglitinides Target: insulin release
48
Name 2 insulin sensitizers. Which goal do they target?
1. Biguanides 2. Thiazolinediones Target: increase insulin sensitivity
49
Name one enzymatic inhibitor. Which goal does it target?
Alpha-glucosidase inhibitors Target: decrease blood glucose
50
Which drug increases glucose excretion?
Canagliflozin
51
MOA of sulfonylureas
1. Bind to K+ channel 2. Block K+ channel 3. Depolarize cell 4. Increase intracellular Ca+ 5. Insulin release
52
MOA of Meglitinides (Repaglinide)
1. Regulate K+ flux through K+ channels 2. Overlap w/ Sulfonylureas in binding site 3. Rapid onset - peak effect within 1 hr
53
What drug is a Biguanide?
Metformin (Glucophage)
54
MOA of Metformin (Glucophage) (most commonly prescribed!)
1. Stimulates glycolysis in tissue 2. Increase glucose removal 3. Activates AMPK 4. Decreases gluconeogenesis 5. Slows glucose absorption from GI 6. Decreases plasma glucagon levels
55
Which drugs are thiazolinediones?
Pioglitazone Rosiglitazone
56
MOA of Pioglitazone and Rosiglitazone
1. Acute post-receptor mimetic activity 2. Bypass insulin receptor 3. Stimulate signaling cascade at PPAR gamma receptor 4. Work in liver, muscle, adipose
57
Which drugs are alpha-glucosidase inhibitors
Acarbose (Precose) Miglitol (Glyset)
58
MOA of Acarbose (Precose) and Miglitol (Glyset)
Inhibit alpha-glucosidase, a brush border enzyme, decreasing carb absorption after meals
59
Why does Acarbose and Miglitol cause GI distress?
They prevent breakdown of carbs, so your stomach will hurt
60
What drugs are incretin-related drugs?
Exenatide Sitagliptin
61
MOA of incretin-related drugs (Exenatide and Sitagliptin)
Exenatide: binds GLP-1 receptors and NOT degraded by DPP-4 Sitagliptin: inhibits DPP-4
62
What does Amylin maintain?
Glucose homeostasis
63
What is Amylin?
37 amino acid protein secreted with insulin
64
MOA of Amylin
1. Decrease glucagon secretion 2. Slow gastric emptying 3. Decrease appetite
65
Which drug is an Amylin analog given by injection at mealtime?
Pramlintide
66
Which drug is a sodium-glucose cotransporter 2 (SGLT2) inhibitor?
Canagliflozin
67
MOA of Canagliflozin
1. Block Na+-glucose co-transporter in kidney 2. Decrease glucose reabsorption 3. Increase excretion of glucose
68
This hormone increases cAMP production and facilitates catabolism of stored glycogen
Glucagon
69
What pathways does glucagon increase?
Gluconeogenesis Ketogenesis
70
What does glucagon mimic in cardiac tissue?
B-adrenergic receptor cAMP effects
71
What does glucagon do in smooth muscle?
Relax small intestine
72
Counter hormone to insulin
Glucagon
73
Causes glycogen breakdown to glucose and signals through glucagon receptor (GPCR linked to Gs)
Glucagon
74
Clinical uses of glucagon (4)
1. Treat hypoglycemia 2. Diagnose endocrine disorders 3. B-blocker poisoning 4. Radiology of the bowel

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