DIABETES AND ANTI- LEC# 23

Tabinda azim
DIABETIC DRUGS IUIC
 OBJECTIVES

Diabetes introduction
Types of diabetes
Anti diabetics
Kinetic and dynamics of anti diabetic drugs
S/E
Interactions
 DIABETES
Diabetes is a chronic medical condition that occurs
when the body is unable to properly regulate blood
glucose (sugar) levels.
 This happens due to either the inability of the pancreas
to produce enough insulin (a hormone that helps regulate
blood sugar)
or the body's inability to effectively use the insulin it
produces.
Insulin allows glucose to enter cells, where it is used
for energy.
0 TYPE I DIABETES
• selective beta cell (B cell) destruction and severe insulin
deficiency
0 TYPE II DIABETES
• decrease in the circulating concentration of insulin insulin
deficiency
• decrease in the response of peripheral tissues to insulin
insulin resistance
 TYPE I DIABETES

0 The disease is characterized by an absolute

deficiency of insulin due to destruction of β
cells.
0 Loss of β-cell function results from
0 autoimmune-mediated processes that may be
triggered by viruses or other environmental
toxins
0 Without functional β cells, the pancreas fails to
respond to glucose, and a person with type 1 diabetes
shows classic symptoms of insulin deficiency
0 Polydipsia ????
0 Polyphagia ????
0 polyuria, and weight loss).
0 Type 1 diabetics require exogenous insulin to avoid
severe hyperglycemia and the life-threatening
catabolic state of ketoacidosis
0 A burst of insulin secretion occurs within 2 minutes
after ingesting a meal, in response to transient
increases in circulating glucose and amino acids.
0 This lasts for up to 15 minutes, followed by the
postprandial secretion of insulin.
0 However, without functional β cells, those with type 1
diabetes can neither maintain basal secretion of
insulin nor respond to variations in circulating
glucose
0 Treatment:
0 A person with type 1 diabetes must rely on exogenous
0 insulin to control hyperglycemia, avoid ketoacidosis, and
maintain acceptable levels of glycosylated hemoglobin
(HbA1c ).
0 What is diabetic ketoacidosis (DKA)?

0 Diabetic ketoacidosis (DKA) is a life-threatening condition that

develops when cells in the body are unable to get the sugar
(glucose) they need for energy
0 When the sugar cannot get into the cells, it stays in the blood.
The kidneys filter some of the sugar from the blood and
remove it from the body through urine.
0 Because the cells cannot receive sugar for energy, the body
begins to break down fat for energy.
 diabetic ketoacidosis.
0 When this happens, ketones, or fatty acids, are produced
and enter the bloodstream, causing the chemical
imbalance (metabolic acidosis) called diabetic
ketoacidosis.

0 The two common ketones produced in humans are

0 acetoacetic acid and β-hydroxybutyrate.
0 Ketoacidosis can be smelled on a person's breath. This is
due to acetone,
 B. Type 2 diabetes

0 Type 2 diabetes accounts for greater than 90% of

cases.
0 Type 2 diabetes is influenced
0 by genetic factors,
0 aging,
0 obesity,
0 and peripheral insulin resistance, rather than
autoimmune processes
 Cause
0 Type 2 diabetes is characterized by a lack of
sensitivity of target organs to insulin
0 In type 2 diabetes, the pancreas retains some β-cell
function, but insulin secretion is insufficient to
maintain glucose homeostasis in the face of
increasing peripheral insulin resistance.
0 The β-cell mass may gradually decline over time in
type 2 diabetes.
0 In contrast to patients with type 1, those with type 2
diabetes are often obese. Obesity contributes to
insulin resistance, which is considered the major
underlying defect of type 2 diabetes
 2. Treatment:
0 Weight reduction,
0 exercise,
0 and dietary modification decrease insulin
resistance and
0 correct hyperglycemia in some patients with
type 2 diabetes.
0 However, most patients require pharmacologic
intervention with oral glucose-lowering agents.
 Treatment of DM
0 INSULIN AND INSULIN ANALOGS
0 Oral hypoglycemic agents
 INSULIN
Structure of human proinsulin and insulin

Insulin is a hormone consisting of 2 polypeptide chains.

Each chain is composed of a specific sequence of amino acid
residues connected by peptide bonds. In humans, chain A
has 21 amino acids, and chain B has 30.

Insulin is a polypeptide hormone formed, after elimination

of C peptide by hydrolysis, of two chains of 21 and 30 amino
acids, connected by two disulfide bridges.

It is secreted by the ß cells of the islets of Langerhans of the

pancreas and exerts an hypoglycemic action.
0 Stimulants of Insulin release
0 Glucose, mannose
0 certain amino acids eg, leucine, arginine
0 Glucagon
0 Cholecystokinin Cholecystokinin is secreted by cells of the
upper small intestine. acts as a hunger suppressant.
0 & vagal activity
0 Inhibitors of Insulin release
0 Somatostatin
0 Leptin (adipocytes)
0 Chronically elevated glucose
0 Half-life of circulating insulin is 3–5 minutes
Insulin Receptor
Result of Insulin receptor activation &
phosphorylation cascade
0 Translocation of glucose transporters (especially GLUT
4) to the cell membrane with a resultant increase in
glucose uptake
0 Increased glycogen synthase activity
0 Increased glycogen formation
0 Effects on protein synthesis
0 Activation of transcription factors that enhance DNA
synthesis and cell growth and division.
 Insulin Secretion
0 ↑ intracellular ATP
levels

0 close the ATP-

dependent potassium
channels

0 ↓ outward potassium
efflux

0 depolarization of the
beta cell

0 opening of voltage-gated
calcium channels

0 ↑ intracellular calcium
triggers
0 secretion of insulin
 Glucose Transporters:
Transporter Tissues Function

Glut 1 All tissues, especially Basal uptake of glucose;

red cells, brain transport across the blood brain
barrier

Glut 2 B cells of pancreas; Regulation of insulin release,

liver, kidney; gut other aspects of glucose
homeostasis

Glut 3 Brain, Kidney, Uptake into neurons, other

placenta, other tissues tissues

Glut 4 Muscle, adipose Insulin mediated uptake of

glucose
Glut 5 Gut, kidney Absorption of fructose
 SOURCE OF INSULINS
0 Purified porcine pigs
0 Purified bovine cattle buffalo
0 Human(recombinant)
0 Human insulin analogs
(Genetically engineered)
Insulin preparations
Ultra short/ rapid
Lispro
Aspart
Glulisine
Short-acting insulins
Insulin injection (regular)
Intermediate-acting insulins
Isophane insulin suspension
Insulin zinc suspension
Long acting
Extended insulin zinc suspension (ultralente)
Insulin glargine
Insulin detemir
 Insulin Unit
0 Activity is expressed in UNITS
0 24 unit/ mg
0 One International Unit is defined as activity of insulin
that would lower BGL in 2 kg healthy rabbit from 120
to 40 mg per 100 ml