Antidiabetics I Flashcards
What type of disorder is diabetes?
metabolic
hyperglycemia
Diabetes occurs when what 2 things happen?
- pancreas does not produce enough insulin
2. body cannot effectively use insulin it produces
4 types of diabetes
- T1D
- T2D
- gestational diabetes
other: impaired glucose tolerance and impaired fasting glycemia
What type of diabetes is insulin dependent?
T1D
What can cause T1D?
B cells destroyed
autoimmune
viral
What type of diabetes is characterized by insulin resistance?
T2D
In normal population insulin secretion is _____ to insulin sensitivity
inversely proportional
Genetic defects of B cell function could be what?
MODY (maturity onset diabetes of young)
What is MODY?
several hereditary forms of diabetes caused by mutations in autosomal dominant gene
Gestational diabetes can cause increased risk of
pre-eclampsia
depression
require C section
What is the current rate of diabetes in America and what is it predicted to be in 2050?
1/10
1/3
T/f diabetes is related to low income
true
t/f India has about 1/3 of the world’s diabetes
false
China
significant complications from diabetes
- CVD
- nerve damage
- kidney damage
- foot damage
insulin brings glucose where?
- liver
- fat
- muscle cells
4 treatments of hyperglycemia
- insulin and its analogs
- insulinotropic agents
- insulin sensitizing agents
- a-glucosidase inhibitors
t/f insulin administration is the only effective treatment for T2D
false
T1D
When is insulin useful for T2D?
when poor B cell function limits efficacy of oral meds
2 major side effects of insulin
hypoglycemia
weight gain
What is the major limiting factor of glycemic management
hypoglycemia
t/f the frequency of hypoglycemia increases with intensive conventional regiments
true
What type of hormone is insulin?
polypeptide
Insulin is formed after elimination of what?
c peptide by hydrolysis
Insulin is recreated by what cells?
B cells of islets of langherans of pancreas
What type of peptides does insulin belong to?
IGF
Insulin structure
A chain: 21AA
B chain: 30AA
connected by 2 disulfide bridges
Human insulin has close homology with _____ and ____
pig (1AA)
cow (3AA)
How are the chains of insulin assembled?
post-translational modification
with disulfide bridge formation
What two forms can insulin be in?
dimer
hexamer
How does insulin form dimers?
H bonding
How does insulin form hexameters?
zinc ions
The design of insulin analogs has emphasized _______ or ______ of structural elements according to established principles of _______
stabilization or destabilization
protein folding
(SAR) What are good sites of modification of insulin?
solvent exposed side chain extrinsic to receptor binding surface
(SAR) What has been studied to assess it ability to form dimers or hexameters and activate insulin receptors?
different sequences
(SAR) Modify insulin to change what?
ADME
Fast or slow insulin analogs
What type of interactions are in insulin?
dimer dimer contacts
monomer monomer interactions
T/f residues involved in interaction with receptor of insulin cannot be modified
true
Non-hexomeric insulins
NPH
Lisper
Aspart
Glulisine
Shifted isoelectric point insulins
glargine
detemir
Which insulin has a suspension of crystalline zinc porcine insulin?
NPH (non-hexomeric)
Which insulin has a high affinity for serum albumin?
detemir
New long acting insulins
Toujeo
Tresiba
Ryzodeg
How long do new long acting insulins last?
up to 42 hours
What was the 1st fast acting insulin analog engineered by recombinant DNA tech?
lispro
Which insulin enhances hexamer formation without Zn in formula?
glargine
Why are shifted isoelectric point insulins used for?
replace basal level of insulin
may be effective over period of 24h
How do smart insulins work?
circulates in blood, turns on when BG is high
Turns back off when in safe zone
Smart insulins are chemically attached to a _____ polymer with sticky sugar groups. This is mixed with a ____ binding molecule.
biodegradable
sugar
The insulin polypeptides in smart insulin comprise a ____ motif that enables the _____ expression of glycosylated insulin polypeptides
N linked glycan
recombinant
The glycosylated insulin conjugates of smart insulin will be sensitive to ______
serum concentrations of glucose
What is important to know about smart insulin pump?
automatically adjusts insulin levels
- users need to manually adjust when high carb meal
What are biosimilars?
generic copy of biologics
Current biosimilar products
- EPO products
- growth factors
- insulins Biocon
