3. „Regulation of storage and use of carbohydrates, fats
and protein within liver, muscle and adipose tissue
„Facilitation of cellular storage of nutrients following a
meal
„Release of metabolic substrates during fasting
4.
5. „ Synthesized as a preproinsulin
„ After cleavage of signal sequence
proinsulin folds and forms S-S bonds
„ In proinsulin A and B chains are
connected by a C peptide
„ Cleavage of C peptide forms
final product
„ Species differences: biologic activities
overlap but antigenic activities don’t
6. Chromosome no-11
Involves all steps of protein synthesis.
The signal sequence attaches mRNA to Rough
Endoplasmic Reticulum.
Endopeptidase breaks down the prepro-I pro-II
Secretory vesicles-
Insulin+c peptide+ endopeptidase+Zn.
8. ATP decreases ADP levels closing of ATP dependent K
channels K inside cell-60mvolts -50mvactivation of
voltage dependent Ca channels intracellular Ca vesicles
move towards membrane release of insulin.
Meglitinides
9. Polypeptide consisting of an A and B chain
of 21 and 30 aa
„Two chains are linked by a pair of S-S bonds
„An intrachain S-S bond connects 6th and 11th aa
within A chain
„Forms a dimer with 2 Zn ions
Hexameric form
10.
11.
12. RAPID EFFECT
Promotes the uptake &
storage of glucose, fats,
& protein-effects on
liver, muscles and
adipose tissue
Carbohydrate Metb
lipid metabolism
Protein metabolism
LONGTERM EFFECT
Gene transcription
Cell proliferation and
differenciation
Protein synthesis
Growth regulation
13. Promotes Muscle Glucose Uptake and Metabolism
Storage of Glycogen in Muscle
Promotes Liver Uptake, Storage and Use of Glucose
Mechanisms:
inactivates liver phosphorylase
causes enhanced uptake of glucose from the blood
by the liver cells -by increasing the activity of the
enzyme glucokinase
14. Insulin promotes Fat Synthesis and Storage
Synthesis- Insulin promotes glucose transport through
the cell membrane into the fat cells
Storage -Adipose Cells-Insulin inhibits the action of
hormone-sensitive lipase
Insulin deficiency
causes increase metabolic use of fat causing
lipolysis of storage fat and release of free fatty acids
increase plasma cholesterol and phospholipid
excess usage of fats during insulin lack causes
ketosis and acidosis
15. Insulin promotes protein synthesis and storage
stimulates transport of amino acids into the cells (valine,
leucine, isoleucine, tyrosine, phenylalanine)
increases the translation of messenger RNA, forming
new proteins
increases the rate of transcription of DNA genetic
sequences in cell nuclei
inhibits catabolism of proteins
depresses the rate of gluconeogenesis
16. Insulin independent glucose utilization-RBC, WBC,
Liver, Brain, Renal medullary cells (mainly GLUT2 )
Insulin dependent glucose utilization – GLUT4 –
activated by insulin present as intracellular pool of
vesicles.
Insulin enhances production of glucokinase, which
helps phosphorylation to form glucose-6-phosphate
It inhibits glycogen degrading enzyme phosphorylase
17. Impaired or absent ß cell function:
insulin secretion
The insulin deficiency results in unacceptable blood
glucose control
19. Minimizing the complications of diabetes requires:
Early diagnosis and treatment of diabetes
Maintaining HbA1C level < 7%
Achieving HbA1C < 7% requires control of post-
prandial and fasting hyperglycemia
22. Integrated measure of glycaemic control
Non-enzymatic glycosylation of proteins
Rate of glycosylation is directly proportional to glucose
concentration
23. Beef insulin
Pork insulin
Insulin by recombinant DNA technology
Human insulin-recombinant DNA technology
E.coli-prb-Pro-Insulin Recombinant Bacterial
yeast-pyr-Precursor Yeast Recombinant
emp-Enzymatic modification of Porcine Insulin
24. Proinsulin and insulin
High molecular weight polypeptide
Metabolism
„Degraded within the liver and kidneys
„80% metabolized in the liver-H.insulinase
„Half-life of about 5 minutes
„Degraded by hepatic glutathione insulin dehydrogenase
„Enzyme disrupts S-S bonds
25.
26. Insulin lispro- produced by reversing proline and lysine
at the corboxy terminal B28 AND b29
Insuin aspart- The proline at B28 is replaced by
aspartic acid
Insulin glulisine-CSII ( for Contineous Subcutanuous-
Insulin infusion) formed by lycine replacing
asparagine
Rapid absorption from subcutaneous tissue
27. Regular insulin- it is a buffered neutral pH solution of
unmodified insulin stabilized by small amount of zinc.
The insulin molecules self aggregate to form
hexamers around zinc ions. After s.c. injection, insulin
monomers are gradually released by dilution.
peak action occurs by 2-3hrs
Prompt insulin-Zn suspension(Lente Insulin)- two types
Ulta lente- large particles-insolube in water, long acting
Semilente- smaller particles, amorphous shorter acting
NPH or isophane insulin
Intermediate acting insulin
NPH or isophane insulin( Neutral Protamine Hagedorn)
protamne complexes all insulin molecules. Mostly
combined with regular insulin. (70:30) or (50:50)
28. INSULIN GLARGINE
Long acting biosynthetic
insulin analogue
Soluble at pH 4 but
precipitates at neutral pH
Delayed onset of action and
suitable for once daily
administration
Injected at bed time
Lowers night time
hypoglycemia
INSULIN DETRIMER
Has fatty acid side chain
Slow and sustained release
Binds to albumin and released
slowly
Twice daily dosage is needed
29. Type 1 DM and type 2 DM
Diabetic keto acidosis (Diabetic coma)
Non-ketotic hyperglycemia
Hyperosmolar coma- nonketotic hyperglycemia
30.
31. Hypoglycemia-(bld glucose < 60mg)
due to large dose or missed meals symptoms counter
regulatory sympathetic stimulation- sweating, anxiety,
palpitation and tremors
Those symptoms due to deprivation- dizziness, headache,
visual disturbance, hunger
Lipodystrophy- of subcutaneous fat around injection site
Allergic manifestations- contaminant proteins
urticaria, angioedema, anaphylaxis
Edema- short lived dependent edema
Insulin resistance >100 units/day
32. Beta adrenergic blockers prolong hypoglycemia by
inhibiting compensatory mechanisms operating
through beta 2 receptors
Thiazides, furosemide, corticosteroids, oral
contraceptives, salbutamol, nifedipine raise blood
glucose levels
Alcohol can precipitate hypoglycemia by depleting
hepatic glycogen
Lithium, high dose aspirin and theophylline may
accentuate hypoglycemia by enhancing insulin
secretion and peripheral glucose utilization
33. It is a synthetic amylin analogue
Sc injection before meal attenuates postprandial glycemia
Exerts centrally mediated anorectic action
duration-2-3hrs
Reduction in body weght
34. Exenatide- It is a synthetic DPP4 resistant analogue
which activates GLP-1 receptors.
Induces insulin release from pancreatic beta cells
Inhibits glucagon release from pancreatic beta cells
Slows gastric emptying and suppresses appetite by
activating specific GLP-1 receptors
Liraglutide- developed as long acting GLP-1 agonist
T1/2- 12hrs
Injected sc once daily