Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology & Medical Chemistry II > Exam 2: Lecture X, Insulin > Flashcards

Exam 2: Lecture X, Insulin Flashcards

You may prefer our related Brainscape-certified flashcards:
USMLE® Step 1 flashcards AP® Chemistry flashcards Periodic Table flashcards Chemistry 101 flashcards Organic Chemistry 101 flashcards
1
Q

Hallmark of diabetes is…

A

the absent or decreased insulin production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Diabetes mellitus is characterized by…

A

hyperglycemia and profound change of protein,carb, and lipid metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Lack of what responsible for Diabetes mellitus?

A

Lack of insulin, resulting in increased blood glucose level

one of many physiological and biochemical changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Insulin and Glucagon are released in….

A

blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

NaHCO3 and Pancreatic enzymes released in…..

A

Dueodenum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What kind of hormone is Insulin?

A

Anabolic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Islets of Langerhands

A 
Alpha = glucagon = 20% of islets
Beta = insulin/amylin = 75% of islets
Delta = somatostain = 3% of islets
F or PP = pancreatic polypeptide pp = 1% of islets
G cells = gastrin = 1% of islets
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Major types of Diabetes Mellitus

A

Type 1 = 5-10%, insulin dependent
Type 2 = 90-95%, insulin independent
Type 3 = other (pancreatitis, drug therapy)
Type 4 = Gestational diabetes, 7% of pregnancy in USA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Insulin info….

A

MW 6000

51AA, two highly ordered polypeptide chains, joined by disulfide bonds (Chain A = 21 AA)(Chain B = 30 AA) (C-peptide = connecting, 31 AA gets removed by proteolysis)

only insulin has physiological effect

Human pancreas contains 8 mg of insulin, 200 units

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Forms of Insulin

A

Hexamer ( 3 Dimmers)
Dimmer
Monomer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Hexamer form of insulin stored in….

A

pancreatic cells, dissociates into monomers

2 Zn molecules of Zn are coordinated in hexameter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which form of insulin is biologically active?

A

only monomer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Factors controlling insulin secretion?

A

All stimulation (+) increases except Sympathetic Stimulation which will (-) decrease

Glucose principle stimulus, causes greater release of insulin than after IV when taken orally.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Mechanism of Insulin secretion?

A
  1. Glucose transported via GLUT-2 into the beta cells
  2. Change of ATP/ADP ratio and ATP increase
  3. Inhibition of ATP-dependent potassium channels—>depolarization
  4. Wave of depolarization —–> cause opening of calcium channels
  5. Calcium moves inside the cell
  6. Calcium further mobilized from endoplasmic reticulum
  7. Increased calcium concentration —-> stimulates insulin secretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

More info Mechanism Insulin secretion

A

2 phases

  1. Insulin secretion is a tightly regulated process
  2. Insulin secretion provides stable concentrations during fasting/feeding
  3. Insulin secretion is biphasic (1 phase/ 2 phase)
  4. First phase - short lived (1-2 min) - stored hormone
  5. Second phase - delayed phase - stored hormone + new hormone
  6. 1/5 of stored insulin in pancreas secreted daily
  7. Insulin secretion is in pulses every 15-30 minutes
  8. Insulin is secreted into portal circulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Insulin Pharmacokinetics

A
  1. Insulin circulates in blood and lymph
  2. Insulin mostly circulates in a free form (2-4 ng/ml portal blood)
  3. Liver + kidneys + muscles - proteolytic degradation of insulin
  4. Liver - 40% of insulin degraded
  5. Kidneys - 40% of insulin degraded
  6. Insulin 1/2 life: 5-6 min
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Insulin actions

A
  1. Insulin stimulates synthesis of glycogen, protein, and fat
  2. Important target: Liver, Muscles, Fat Cells
  3. Overall effect: Conservation of body fuel supplies
  4. Cell growth and differentiation
  5. Most obvious effect: Reduction of blood glucose level (due to increased glucose transport)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Other effects of insulin

A
  1. Increased transport into the cells of K+, Ca2+, and phosphate
  2. Increase/decrease synthesis of key enzymes
  3. Stimulate cell proliferation in vitro/growth regulation in vivo
  4. Effects upon DNA and RNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Insulin Receptors

A
  1. Specific receptor - transmembrane glycoprotein
  2. Receptor consists of - 2alpha and 2 beta subunits (400 000 MW)
  3. Alpha and beta subunits are linked by disulfide bonds (S-S)
  4. Alpha subunits - entirely extracellular (ligand-binding site)
  5. Beta subunits - transmembrane proteins with tyrosine-kinase activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Resistance to insulin explained by…

A

**Insulin-receptor complex after some time internalize in vesicles - loss of insulin receptors occurs. (Receptor down regulation).

21
Q

Insulin action of receptors

A
  1. Insulin binds with extracellular ligand-binding site
    - Dimerization of the receptor occurs
  2. Beta subunits act upon themselves (autophosphorylation)
    - Beta subunits enhance the action of the kinases on other targets
  3. Typical targets - synthesis of glycogen, lipids, proteins and enzymes
  4. Translocation of glucose transporters (GLUT-4) also takes place
    • GLUT-4 is recruited from Golgi apparatus to plasma membrane
  5. Glucose facilitated diffusion through the glucose transporter
22
Q

Glut 1 location

A

All tissues, Brain RBC

23
Q

Glut 2 location

A

B cells pancreas, liver,kidneys,gut

24
Q

Glut 3 location

A

Brain, placenta

25
Q

Glut 4 location

A

Muscle, adipose tissue

26
Q

Glut 5 location

A

Kidney,gut

27
Q

Insulin effects take place in second/minutes

A

effects on glucose/ion transporters

28
Q

Insulin effects take place in few hours

A

effects on gene transcriptions

29
Q

Insulin effects take place in days

A

effects on cell proliferation and differentiation

30
Q

Glucagon fuel

A
  1. Produced in alpha cells of pancreas and in stomach (21 AA)
  2. Structurally similar to GI hormones (secretin, VIP, gastric inhibitory peptide)
  3. Aminoacids (especially arginine) - physiological stimuli for the secretion
  4. Secretion is stimulated by high protein meal
  5. Secretion is stimulated by low glucose and fatty acids in the plasma
  6. CNS and circulating epinephrine stimulate glucagon through beta-receptors
31
Q

Glucagon Actions

A
  1. Acts upon specific receptors (similar to beta-receptors)
  2. Similar to epinephrine in action
  3. More pronounced metabolic effects, rather than cardiovascular
  4. Can increase rate/force of contraction (sometimes used to treat cardiac failure)
  5. Actions are opposite those of insulin
  6. Increases breakdown of glycogen
  7. Inhibits glycogen synthesis
  8. Both 6 and 7 result in elevation of blood glucose (used to treat hypoglycemia)
  9. Can be administered IM, SC, IV (treatment of hypoglycemia)
32
Q

Major Symptoms Diabetes

A
  1. Hyperglycemia (due to: ↑hepatic output ↓skeletal muscles uptake ↓reduced glycogen synthesis)
  2. Polyuria
  3. Polydipsia (thirst and increased drinking)
  4. Polyphagia
  5. Ketoacidosis (T1DM) fat breakdown to β-hydroxybutyrate (acidosis) and acetone (ketone)
  6. Hyperlipidemia
  7. Muscle wasting
  8. Electrolyte depletion
33
Q

Long term Medical problems of diabetes

A
  1. Neuropathy
  2. Nephropathy
  3. Microangiopathy
  4. Retinopathy
  5. Nonretinal visual problems
34
Q

Insulin Route of Admin

A
  1. Subcutaneous (usual)
  2. Occasionally intramuscularly
  3. Intravenous - (emergency – Regular insulin)
  4. Peritoneal infusion
  5. Intranasal administration
35
Q

Origin of Insulin

A
  1. Early preparations were acidic. Precipitated in tissues. Impurities.
  2. Bovine (discontinued in 1999)
  3. Porcine (discontinued in 2006)
  4. Mixture of bovine and porcine - discontinued
  5. Semisynthetic (chemical alteration of pork insulin) - discontinued
  6. Insulin analogue - chemical alterations of human insulin
  7. “Human” - recombinant DNA
36
Q

Rapid acting Insulin

A

very rapid onset and very short action

Insulin Lispro, aspart, Glulisine

Onset: 1/4 hr
Peak: .5-1.5 hr
Duration: 3-4hr

enters circulation twice as fast as regular, suitable immediately before meals

37
Q

Short acting insulin

A

rapid onset and short action

Humulin R, Novolin R

Onset: .5-1hr
Peak: 2-3hr
Duration 3-6hr

Subcu, IV in emergency only, admin 1 hr before meal. can be mixed with longer acting insulin

38
Q

Intermediate acting insulin

A

intermediate onset and action

Humulin N, Novolin N

Onset: 2-4hr
Peak 6-10hr
Duration, 10-16hr

Given subcu,depot formed and slowly released

39
Q

Long acting insulin

A

slow onset and long action

Lantus, Levemir

Onset: 5-10hr
Peak: 10-16hr
Duration, 18- 24hr

Provide relatively constant release for 24hr, forms stable hexameter upon subcu inj

40
Q

Insulin Conc

A

100U/ml = all insulins in USA/Canada

500U/ml = rare cases of severe insulin resistance

41
Q

Type 1 requires….

A

combo of rapid/intermediate acting insulin

42
Q

Type 2 requires….

A

intermediate or long acting insulin

43
Q

Patients with T1DM require

A

long-term maintenance treatment with insulin

44
Q

Many patients with T2DM ultimately require

A

chronic insulin treatment

45
Q

Insulin Devices

A

pump

Nasal spray (Exubera 2006-2007 Discontinued and Afrezza 2014)

Subnlingual (oralin) in Clincial trials canada
Transderaml patch in clinical trials
Transplantation of pancreatic beta cells

46
Q

Hypoglycemia

A

Insulin shock !!!

  • Anxiety
  • Confusion
  • Blurred vision
  • Cold sweating
  • Tachycardia
  • Hunger

Most common adverse effect of insulin therapy, 60-170 episodes/100 patients/yr

47
Q

Hypoglycemia treatment

A

inject 20g of glucose, ie fruit juice

Glucose iv - 50 ml of 50% glucose for 2 min
Glucagon sc/im - 1 mg of glucagon

48
Q

Local reactions insulin

A

Lipodystrophy (older forms)

Hypertrophy of subcu fatty tissue

infections

local allergic reaction

49
Q

Antigenic response to insulin

A

(Highest-lowest)

Beef >Pork >Highly purified (“single-peak”) pork >Human insulin

Microvascular complications (due to growth-promoting properties)

Weight gain

Increased cancer risk (?)

Pharmacology & Medical Chemistry II (43 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions