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Diabetes and insulin
1. Presented by
Rasel Mahbub
Dept of pharmacy
Jagannath University
2. DM is characterized by elevated blood
sugar levels due to absolute or relative
lack of insulin.
Type 1 diabetes - -cell failure at outset
•Insulin dependent
Type 2 diabetes - Gradual -cell
deterioration
•Early stages: Diet and Oral agents
•Late-stage: Insulin therapy
3. Glycosylated hemoglobin Hb-A1c :
It is used to monitor the plasma glucose
concentration over prolonged periods of
time (4-6 weeks).
Insulin secretion is promoted by ↑ blood
glucose levels, amino acids, GI hormones
and by β-2 agonist.
4. Proinsulin is converted to insulin and C
peptide.
Insulin is referred as the storage hormone
as it promotes anabolism and inhibits
catabolism of carbohydrates, fatty acids
and protein.
In the absence of insulin, most tissues
cannot use glucose and fats/proteins are
broken down to provide energy.
5. Mechanism of action :
Insulin binds to insulin receptors on the
plasma membrane and activates tyrosine
kinase – primarily in adipose tissue,
liver and skeletal muscle.
The Nerves, RBC’s, Kidney, and Lens of
the eye do not require insulin for
glucose transport.
6. Liver :
Insulin increase the storage of glucose as
glycogen in the liver.
It inserts the GLUT-2 glucose transport
molecule in the cell membrane.
It inhibits gluconeogenesis – thus
significantly ↓ glucose output by the liver.
It decrease the protein catabolism.
7.
8. Muscle :
Insulin stimulates the glycogen
synthesis and protein synthesis.
Glucose transport into the cells is
facilitated by GLUT-4 into the cell
membrane.
It inhibits the protein catabolism.
9. Adipose tissue :
Insulin facilitates the storage of
triglyceride by activating plasma
lipoprotein lipase and inhibiting
intracellular lipolysis.
It increase the glucose uptake by
GLUT-4 insertion into the cell
membrane.
10.
11. Insulin is a 51 AA peptide
Not active orally.
Insulin is inactivated by insulinase found
mainly in liver and kidney.
Dose reduced in renal insufficiency
Sources of Insulin :
• Beef pancreas / Pork pancreas
• Human insulin: recombinant DNA origin
12. Human Insulin :
Do not contain measurable amounts of
proinsulin or contaminants.
Diminished antibody
Less allergic reactions
Less lipodystrophy
Preferred in gestational diabetes
16. Adverse effects of Insulin :
Hypoglycemia
Allergic reactions
Lipodystrophy
Others includes
• Seizures
• Coma
17. Mechanisms to reduce blood sugar :
Stimulation of pancreatic insulin release –
Sulfonylureas, Meglitinide
Reduce the bio-synthesis of glucose in
liver – Biguanides (Metformin)
Increase the sensitivity of target cells to
insulin -- Thiazolidinediones
Retard the absorption of sugars from the
GI tract – Acarbose, Miglitol
18.
19. Sulfonylureas :
First generation : Acetohexamide,
Chlorpropamide, Tolbutamide,
Tolazamide
Second generation : Glipizide, Glyburide
– more potent, more efficacious and fewer
adverse effects.
Third generation : Glimiperide
22. Sulfonylureas : Adverse effects :
Hypoglycemia
Cholestatic jaundice
Weight gain
Cross placenta – fetal hypoglycemia.
Chlorpropamide : It can cause water
retention by ↑ release of ADH (SIADH)
Disulfiram-like reaction with alcohol.
23. Repaglinide, Nateglinide :
More rapidly acting insulin enhancers
and shorter duration than sulfonylurea.
Hypoglycemia is the common adverse
effect.
Less weight gain
24. Repaglinide, Nateglinide
The drug has minimal renal excretion thus
useful in patients with DM and impaired
renal function.
It is designed to be taken with each meal
to stimulate insulin release with meal.
If a meal is skipped, so is the repaglinide.
26. Metformin (Glucophage) :
It does not cause hypoglycemia.
It produces a significant ↓ TG and LDL,
and ↑HDL.
There is a serious concern about lactic
acidosis especially in patients with kidney
disease.
27. Thiazolidinediones
Enhance glucose and lipid metabolism
through action on Peroxisome Proliferator
Activated Receptor (PPAR–γ)
Enhance sensitivity to insulin in muscle
and fat by increasing the GLUT 4 glucose
transporters.
E.g. ; Pioglitazone Actos, Rosiglitazone
Avandia
29. Alpha-Glucosidase Inhibitors:
It inhibits -glucosidase which converts
dietary starch and complex
carbohydrates into simple sugars
It reduces absorption of glucose after
meals.
The main side effects includes flatulence
and diarrhea.
Acarbose (Glucobay) , Miglitol (Glyset)
30.
31. Glucagon like Peptide : GLP-1 analog :
Xenatide : (Byetta) :
GLP is an incretin released from the small
intestine which increase the glucose
dependent insulin secretion.
Xenatide suppress glucagon release and
reduce appetite
It is administered by SC injection.
34. Sitagliptin (Januvia) is an oral anti-
diabetic drug.
It inhibit the dipeptidyl peptidase 4 (DPP-
4), an enzyme which inactivates the
incretins GLP-1 and GIP, that are released
in response to a meal.
It potentiates the secretion of insulin and
suppress the release of glucagon by the
pancreas.
35. Glucagon :
It has positive inotropic action and
chronotropic action on the heart.
It acts by stimulation of glucagon
receptors and not through beta 1 receptors.
This is the basis for using glucagon in beta
blocker overdose.