INSULIN

Struktur Bangun Insulin

 Proinsulin C peptide
Ca2+-dependent Insulin
endopeptidases
MW 5808
PC2
(PC3)
A Chain

B Chain
PC3
 Insulin terdiri atas :
 Rantai A 21 asam amino,
 Rantai B 29 asam amino.
 Th 1936 (Scott & Fisher) : Zn / dlm pancreas kompleks dg Zn-
koloidal  d.o.a sbg Protamin Zinc Insulin / PZI) : 48-72 jam
 Short-acting : solub-crystalline Zn-Ins  o.a 30 mnt, d.o.a 7 jam
 Intermediate & long acting/lente: 30% endapan amorf Zn - Ins
+ 70% bent. kristal sukar larut Zn-Ins), o.a 2 jam; d.o.a < 24 jam
 Ultra short / lispro: proline/ B28)  ditukar dg lysine / B29 
mencegah hexamerisasi  onset cepat, tmax < 1 jm, d.o.a 3-4 jam
 Glargine / analog l.a.: glycine / A 21; plus 2 arginine pd
B30+B31lebih stabil  abs 2-4 j; t.max 4 jam; d.o.a 24-30 jam.
Insulin release: normal levels
 Units: 1 U = 36 µg, i.e. 28 U/mg
 Daily secretion in humans: 40 - 50 U
 Basal plasma insulin: 12 µU/ml
 Postprandial insulin: up to 90 µU/ml
120
Meal
Glucose, mg/dl

100

Insulin, U/ml
80

80 60

40

Basal 20

Minutes 0 30 60 90 120
Insulin metabolism
 Secreted into portal circulation
 50% of degradation in liver
 50% of degradation in other target tissues
and kidney
 Enzymatic degradation follows receptor-
mediated endocytosis
 Plasma half-life: 3 - 5 min.
 Circulates as free monomer

 Distribution volume approximates that of

the extracellular fluid
Insulin : mechanism of action

Cell-surface receptors:

a subunits contain
insulin binding sites

plasma membrane

b subunits have tyrosine

kinase activity
Effects of insulin:
Stimulates Inhibits
 Liver
glycogen synthesis glycogenolysis
triglyceride synthesis ketogenesis
gluconeogenesis
 Skeletal Muscle
glucose uptake
protein synthesis protein degradation
glycogen synthesis glycogenolysis

 Adipose tissue
glucose uptake
triglyceride storage lipolysis
Promotes anabolic Inhibits catabolic
processes processes
Clinical Uses of Insulin
 Type 1 diabetes mellitus
 Type 2 diabetes mellitus uncontrolled on maximal
combination therapy with oral agents
 Gestational diabetes
 Hyperglycemic emergencies
 Total pancreatectomy patients
 Acute or chronic hyperglycemia provoked by:
 Infection or trauma
 Steroid therapy
 Endocrinopathies such as hyperthyroidism
 Other types of secondary diabetes
Any of these conditions may increase the requirement
of patients already on insulin
Sources of Insulin for Clinical Use

Human insulin produced by recombinant

technology has replaced bovine and porcine
insulin preparations

 Available as 100 or 500 U/ml

 labeled U-100 or U-500

 Most available without prescription

 exceptions- U-500, lispro, and glargine
Insulin Preparations
Ultra fast/ultra lispro
from LillyDiabetes.com

short-acting
regular
Short-acting

Plasma [Insulin]
NPH
Intermediate-
acting
lente

ultralente
Long-acting

from lantus.com
glargine
Ultra long-acting
0 4 8 12 16 20 24
Insulin Preparations
 Ultrafast / ultra short-acting: insulin lispro
 lysine [B28], proline [B29]

Insulin
lispro

PRO
LYS
LYS
PRO
Ultrafast/ultra short-acting insulin
 Insulin lispro
 monomeric
 not antigenic
 the most rapidly acting insulin

 used within 15 minutes of beginning a meal

 short duration of action- must be used with

longer-acting preparation for Type 1 diabetes
unless used for continuous infusion
Short-acting insulin
 Regular insulin (insulin injection)
 denoted on vial by “R”
 zinc insulin crystals in a neutral, nonbuffered,
suspending solution
 can be given I.V.
Intermediate-acting insulin
 NPH insulin (Neutral protamine Hagedorn,
isophane insulin suspension)
 denoted on vial by “N”

 stoichiometric mixture of regular and protamine

zinc insulin (complexed with excess of positively

charged fish sperm protamine)
 LENTE insulin (insulin zinc suspension)
 denoted on vial by “L”

 30% SEMILENTE insulin (amorphous precipitate

of insulin with zinc in acetate buffer)
 70% ULTRALENTE insulin
 Long-acting insulin
 ULTRALENTE insulin (extended insulin zinc
suspension)
 denoted on vial by “U”

 delayed onset
 prolonged action
 acetate buffer
 excess zinc large crystals with low solubility
 Ultra long-acting insulin
 Insulin glargine
 Recombinant insulin analog that precipitates in the
neutral environment of subcutaneous tissue
 Peakless- prolonged action
 Administered as single bedtime dose

Insulin
glargine ASN
GLY

ARG

ARG
Adverse Effects of Insulin Therapy
 Hypoglycemia
 Especially dangerous in Type 1 diabetics
 Glucose or glucagon treatment

 Allergy and resistance to insulin

 Local cutaneous reactions or systemic
 Switch to less antigenic form or desensitization
 Lipohytertrophy
 Due to lipogenic effect of insulin when small area used for
frequent injections
 Absorption from such sites is unpredictable
 Lipoatrophy
 Due to impurities: switch to highly purified insulin
 Lipogenic effect of insulin can repair lesion
 Insulin edema- transient, rare
 
TERIMA
KASIH