There are four categories of Diabetes

mellitus :
1. Type 1 Diabetes mellitus (insulin-
dependent diabetes)
2. Type 2 Diabetes mellitus (non insulin-
dependent diabetes)
3. Type 3 Diabetes mellitus (refer to
multiple other spesifik causes of an
elevated blood glucose)
4. Type 4 Diabetes mellitus (Gestational
diabetes mellitus)
- Insulin is a small protein with a molecular weight
in humans of 5808
- Insulin containts 51 amino acids arranged in two
chains (A & B) linked by disulfide bridges
- Proinsulin is a long single-chain protein
molecule
- Proinsulin is hydrolyzed into insulin and a
residual connecting segment called C-peptide
by removal of four amino acids
- Proinsulin is processed within the golgi
apparatus and packaged into granules
- The entire human pancreas contains up to 8 mg
of insulin.
Insulin is bound by specialized receptor
that are found on the membrane of most
tissues. The receptor name are insulin
receptor substrate – 1 and – 2
Glucocorticoid lower the afinty of insulin
receptor (IRS-1, IRS-2)
- Insulin is released from pancreatic B cells
in response to variety of stimulies
- Several stimulants that involved in insulin
secretion :
 Other sugars (eg.mannose)
 Certain amino acids (eg, leucine,
arginine)
 Vagal activity
- The mechanism of insulin secretion :
 In the resting cell with normal ATP levels 
potassium diffuses down its
concentration gradient through ATP-
gated potassium channel  maintaning the
intracellular potential at a fully polarized
 insulin release is minimal.
 If glucose concentation rises  ATP production
increases  potassium channel close 
depolarization of the cell  voltage-gated
calcium channels open  more calcium
enter the cell  increased intracelluler
calcium  triggers secretion of the hormone.
(Insulin secretagogues groups have same
mechanism)
 Hyperglycemia
(glucose concentration rises)

ATP production 

Intracellular ATP levels 

ATP-dependent potassium channel Close

Decreased outward potassium efflux

Depolarization of B cells

Opening of Voltage-gated calcium channel

More calcium enter the cells

Intracellular calcium 

Triggers secretion of insulin hormone
Commercial insulin preparations
differences in :
- The recombinant DNA production
techniques
- Amino acid sequence
- Concentration
- Solubility
- Time of onset and duration of their
biologic action.
Four principal types of insulins are :
1. Rapid-acting with very fast onset and
short duration
2. Short-acting with rapid onset of action
3. Intermediete-acting
4. Long-acting with slow onset of action
- Intermediate or long-acting insulins are
used to provide basal or background
coverage
- Rapid-acting or short insulins are used to
meet the mealtime requirements
- Alternative intensive regiment referred
to as Multiple Daily Injections (MDI) use
long-acting or intermediate-acting
insulins with multiple boluses of rapid-
acting or short-acting insulin.
1. Rapid-acting insulin
- Permit more physiologic prandial insulin
replacement.
- Duration of action is rarely more than 3 – 5 hours.
2. Short-acting insulin
- Soluble crystalline zinc insulin
- Its effect appears within 30 minutes and peaks
between 2 & 3 hours after subcutaneous injection
- The only type that should be administered
intravenously
- Particularly useful for IV therapy in the
management of diabetic ketoacidosis, after
surgery or during acute infections
- In high concentration : this insulin molecules self
agregate in antiparallel fashion  form dimers
 stabilize around zinc ions  create insulin
hexamers.
3. Intermediate-acting and long-acting
insulin
a. Lente insulin
b.NPH (Neutral Protamine Hagedorn, or
isophane) insulin
c. Ultralente insulin
d.Insulin glargine
 Insulin → enzyme dephosphorylation →
inhibition of glycogenolysis dan lipolysis
 Insulin → pyruvat dehydrogenase
enzyme activation → pyruvat oxydation ↑
→ pyruvat storage ↓ → glukoneogenesis
↓
a. Portable pen injectors
b. Continuous subcutaneous insulin
infusion devices (CSII, Insulin Pump)
c. Inhaled insulin
A. Hypoglycemia
B. Insulin allergy
C. Immune insulin resistance
D. Lipodystrophy at injection sites
 THANK YOU
Be A Good Doctor By Making Correct
Prescription