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Hernita Taurustya, MD
• Insulin resistance
Type III (other type)
• Drugs (corticosteroid), endocrinopathy,
Gestational DM
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Pancreas
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Regulation of insulin secretion
• Stimulants of insulin release:
– Sulfonylureas
– Insulin
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• Proinsulin:
– A chain, B chain, and C peptide:
– Proteolytic enzyme cleaves proinsulin insulin
• Insulin: 51 amino acids
– A chain: 21 AA
– B chain: 30 AA
– Linked by 2 disulphide bridges (A7-B7 and A20-B19)
– and another disulphide bridge (A6-A11)
• C peptide:
– No clear physiological function
– Used as a marker of insulin secretion
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Regulation of Glucose Transport by
Insulin
• Glucose enter cells by diffusion through
glucose transporter (GLUT)
• Without insulin, the GLUT are retained in
vesicles within the cytosol
• Insulin facilitates translocation of GLUT to
cell membrane, thus allowing the passage
of glucose into the cells
• Disturbance of glucose transport may lead
to type II diabetes.
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Preparations
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•Rapid-acting – aspart, glulisine, lispro,
human insulin recombinant inhaled
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Indications of insulin therapy
All T1DM
T2DM uncontrolled by diet and/or
hypoglycemic agents
Postpancreatectomy diabetes
Gestational diabetes
Diabetic ketoacidosis & hyperglycemic
nonketotic
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Goals of insulin therapy
fasting blood glucose conc. 90-120 mg/dL
two-hour postprandial < 150 mg/dL
HbA1c < 7%
Factors that determine insulin SC absorption:
1.Site of injection – abdominal wall >>
2.Subcutaneous blood flow – to ↑: massage, hot
baths, exercise
3.Volume & concentration of the injected insulin
4.Depth of injection (IM more rapid onset of action)
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Adverse reactions
Hypoglycemia – counter-regulatory
hormones (epinephrine, norepinephrine,
cortisol, growth hormone, GLUCAGON)
Insulin allergy
Lipoatrophy & lipohypertrophy
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Drugs that cause Drugs that cause
hyperglycemia
hypoglycemia
Epinephrine
Ethanol Glucocorticoids
Beta blockers – Atypical antipsychotic
Phenytoin
mask effect
Calcium channel
Salicylates blockers
Diuretics
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1. Insulin secretagogues
a. Sufonylurea
b. Meglitinide:
c. D-phenylalanine derivatives
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• ↑ insulin release from
the pancreas
• Reduction of serum
glucagon levels by
stimulate release of
somatostatin
• Closure of potassium
channels in
extrahepatic tissues
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• ADVERSE EFFECTS
– Hypoglycemia
– Allergic reaction
– GI disturbances
– Cholestatic jaudice
• INTERACTION
– Sulfonamides, clofibrate, dicumarol, salicylates
displace the SU from protein binding increase
hypoglycemic effect
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• INDICATION
– Type 2 DM which fail with diet therapy
• Contraindications:
– Type 1 DM,
– pregnancy, lactation,
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BIGUANIDES
metformin, phenformin, buformin
metformin alone or in combination with a SU
improves glycemic control & lipid conc.
EUGLYCEMIC
Reduce glucose levels by:
1. ↓ hepatic glucose production
2. ↑ insulin action in muscle & fat (AMPK)
3. slowing glucose absorption from GIT; ↑
glucoselactate
4. reduction of plasma glucagon levels
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BIGUANIDES
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THIAZOLIDINEDIONES
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THIAZOLIDINEDIONES
PREPARATIONS
– Pioglitazone (Actos®)
– Rosiglitazone (Avandia®)
• Tablet 2, 4, 8 mg
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THIAZOLIDINEDIONES
• Might be benefit to prevent development of type
2 DM
• EUGLYCEMIC
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Cardiac effects:
• Inotropic and chronotropic effects (similar to b-
agonist)
Other effects:
• relaxation of intestine
Clinical uses
• Severe hypoglycemia
• Endocrine diagnosis
• Beta blocker poisoning
Rapid degradation in the liver, kidney, plasma,
and tissues
Plasma T1/2: 3-6 minutes need continous iv
infusion.
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An antihypertensive agent
Potent hyperglycemic action when
given orally
Mechanism:
• Potassium channel opener (opposite to SU)
• Inhibits insulin secretion
• Modest capacity to inhibit peripheral
glucose utilization
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Indications
• Treatment of hypoglycemia due to hyper
insulinemia (such as in insulinoma), and other
form of hypoglycemia
• Hypertension
Side effects
• Nausea, vomiting
• Hypertrichosis
• Na and fluid retention, hyperuricemia,
thrombocytopenia, and leukopenia
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American Diabetes Association
Standards of Medical Care in Diabetes-
2014
Pharmakology Katzung
Phatofisiology Sylvia
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