current insulin

1. Current Updates on Insulin
Presented by
Anshuman Singh
M.Pharm(Pharmacology)

2. Contents
• Background
• Types
• How insulin works
• Preparation of insulin
• Methods of delivering insulin
• Marketed products
• Side effects and ADRs
• Reference

3. Background of Insulin
• Discovered by Banting and Best - 1921
• Fredrick G. Banting & Charles H. Best -
• Canadian Scientist – Extracted Insulin
from Dog pancreas
• 2 chain Polypeptide – 51 amino acids & MW 6000
• Chain-A has 21 and Chain-B has 30 amino acids –
connected by two disulfide bonds
• Source: Porcine, Bovine and Human (Pork = human)
• Synthesized in β cells of islets of pancreas –
• single chain 110 amino acids (Preproinsulin)
• Proinsulin – 86 amino acids
• Connecting “C” peptide (35 amino acids)
• removed by proteolysis in Golgi apparatus –Insulin

4. Diabetes Mellitus
Hyperglycemia, glycosuria, hyperlipidaemia, negative nitrogen
balance and ketonaemia
Pathological changes: thickening of capillary basement membrane,
increase in blood vessel wall matrix, and cellular proliferation
 Consequences: Lumen narrowing, atherosclerosis, sclerosis of
glomerular capillaries, retinopathy, neuropathy and peripheral vascular
insuffficency
 Causes of pathological changes: Enhanced non-enzymatic
glycosylation of tissue proteins and accumulation of large amounts of
sorbitol
Glycosylated haeoglobin (HbA1c ) – Index of protein glycosylation

5. Diabetes Mellitus - Types
Type I: Insulin dependent DM (IDDM) / Juvenile onset
diabetes – low circulating insulin level -prone to
ketoacidocis
– destruction of β cells in pancreatic islets
– Type IA – antibodies destroying β cells
– Type IB: Idiopathic, no β cell antibody detectable
– Low degree of genetic predisposition
Type II- Noninsulin-dependent DM (NIDDM): no loss
of moderate loss of β cell, low/normal/high insulin in
circulation, no anti- β-cell antibody – genetic
predisposition.

6. Causes of NIDDM
• (1) Abnormality in gluco-receptor in β cell – needs higher
conc. of glucose;
• (2)Relative β cell deficiency
– Down regulation of insulin receptors in peripheral tissues
– Many Hypertensives are hyperinsulinamic –
normoglycaemic but dyslipidaemia
hyperuricaemia, abdominal obesity (metabolic syndrome)
– Insulin Resistance – Excess of hyperglycamic hormones
• Other Types: Type III – LADA and MODY;
Type IV – Pancreactomy and gestational diabetes mellitus
(GDM)

7. Action of insulin
• Meal derived glucose, amino acids, fatty acids and
fuel storage.
• Major anabolic hormone – synthesis of glycogen,
lipids and proteins
• Facilitates glucose transport across cell membrane
– skeletal muscle and fats - Liver, brain, RBC,
WBC and renal medullary cells are independent.

8. • Intracellular utilization of glucose – phosphorylation
to form Glucose-6-PO4 – increased production of
glucokinase – also glycogen synthase
• Inhibits gluconeogenesis from protein, FFA and
glycerol (diverted to liver) – by decreasing synthesis
of (gene mediated) phosphoenol pyruvate
carboxykinase.
• Inhibits lipolysis in adipose tissues – favours
triglyceride synthesis – in diabetes, increased FFA
and glycerol (Acetyl-CoA) – ketone bodies

9. Effect of insulin on glucose uptake and
metabolism

10. Preparations of Insulin
-> Classically – produced from beef and pork pancreas
• Contains 1% (10, 000 ppm) other proteins –
proinsulin, polypeptides,
• pancreatic proteins etc.) – potentially antigenic
• Replaced with highly purified pork/beef
insulin/recombinant human
Types of preparations – Regular (Soluble) Insulin
• Buffered neutral pH solution unmodified insulin
stabilized by small amount of zinc
• Forms hexamers around zinc ions – released slowly
and gradually by dilution on SC administration
• Peak onset 2- 3 hours and lasts for 6-8 hours

11. Methods of delivering insulin
• Insulin pump
• Prefilled insulin syringe
• Insulin pen
• Insulin patch
• Insulin Inhaler
• Insulin pills

12. Insulin pen
• An insulin pen is used to inject insulin for the treatment
of diabetes. Insulin is a hormone produced by the pancreas.
It is composed of an insulin cartridge (integrated or bought
separately) and a dial to measure the dose, and is used with
disposable pen needles to deliver the dose. It was
introduced and marketed as NovoPen by the Danish
company Novo Nordisk.

13. Insulin pump
Insulin pumps are small, computerized devices that
mimic the way the human pancreas works by delivering
small doses of short acting insulin continuously (basal
rate). The device also is used to deliver variable amounts
of insulin when a meal is eaten (bolus).

14. Insulin patch
The adhesive patch monitors blood sugar, or glucose. It
has doses of insulin pre-loaded in very tiny microneedles,
less than one-millimeter in length that deliver medicine
quickly when the blood sugar levels reach a certain
threshold. When blood sugar returns to normal,
the patch's insulin delivery also slows down.

15. Prefilled insulin syringe
• Before using a prefilled syringe, allow the syringe to warm for 5
to 10 minutes. Gently roll the syringe between your hands to
warm the insulin. If the syringe contains a cloudy insulin, make
sure all of the white powder is dissolved before giving the shot.

16. Insulin Pills
• Insulin pills, also known as insulin tablets,
remain at an early stage of clinical trials with
several companies racing to establish this as a
credible alternative to insulin injections.

17. Insulin Inhaler
• Inhalable insulin is a powdered form
of insulin, delivered with an inhaler into the
lungs where it is absorbed. In general inhaled
insulins have been more rapidly absorbed .

18. Other uses of insulin
Cell culture
Wounds healing
parenteral nutrition
Ant ageing
Cardioprotective
Septic shock
Cancer treatment

20. Insulin mixtures

21. Current marketed products

24. Reference
• Pubmed
• Slideshare
• Researchgate
• Researchscholar