This document discusses diabetes mellitus, including its signs, symptoms, types, and complications. It also covers the physiology of insulin production and secretion by the pancreas, as well as the mechanisms and effects of insulin. Different insulin preparations are described based on source, onset and duration of action. Guidelines for insulin administration and considerations for special cases and drug interactions are provided.

2. DIABETES MELLITUS:
 Metabolic disorder characterised by
hyperglycemia, glycosuria, hyperlipemia,
Negative nitrogen balance and some
time ketonemia
 Sign and Symptoms
 Increase in frequency of urination
(Polyuria)
 Excessive thirst (polydipsia)
 Excessive eating (Polyphagia)
 Fatigue
 Unexplained weight loss etc

3. Why diabetes should be controlled?
Uncontrolled leads to complications:
ACUTE
 Diabetic Ketoacidosis (DKA)
 Hyperglycemic hyperosmolar state
(HHS)
CHRONIC
 Retinopathy, Neuropathy,
Nephropathy- (microvascular)
 Coronary & peripheral vascular
disease and cerebrovascular
disease- (macrovascular)
 other

4. TYPES OF DIABETES MELLITUS:
Type 1 / Insulin Dependent
Diabetes Mellitus (IDDM)
Characterized by β-cell (pancreatic
islets) destruction leading to absolute
insulin deficiency
Type 2 / Non Insulin Dependent
Diabetes Mellitus (NIDDM)
Characterized by insulin resistance
and relative insulin deficiency

5. TYPE 1 DM TYPE 2 DM
Juvenile onset (<30 yrs) Maturity onset
β- cells are destroyed: NOT destroyed: relative
absolute deficiency deficiency
Autoimmune(type 1 a) mild or severe
Idiopathic (type 1 b)
Less common & less Very common & high
genetic predisposition Genetic
predisposition
Insulin is must Controlled by diet
change, exercise & oral
drugs: Insulin when
other fails

6. INSULIN:
 Discovered in 1921 by Banting
and best
 Banting and Macleod got nobel
prize in 1923
 Leonard Thompson: First
patient to receive insulin

12. Diabetes mellitus contd…….
Insulin is synthesised & secreted by Pancreas

13. PANCREAS
a) Exocrine Gland
b) Endocrine Gland
Exocrine Gland:
 secretes enzymes

14. ENDOCRINE
Islets of Langerhans contains:
 α cells : secrete glucagon.
 β cells : secrete insulin.
 δ cells : secrete gastrin &
somatostatin

15.  Insulin is polypeptide 51
aminoacid (MW 6000). Contains
two chains; chain-A 21 aa &
Chain-B 30
 These chains are held together
by two inter-disulfide bonds &
one intra disulfide bond
 Pork insulin differ by one aa
where as Beef by two aa differ

16. SYNTHESIS
 Synthesized as preproinsulin
(110 aa) in rough ER (single
chain)
 Preproinsulin → proinsulin (86 aa;
molecule fold )
 Transported to Golgi apparatus
 Converted to insulin & C-peptide
 Stored in the granules of β cells

17. C peptide
Proinsulin
A Chain
B Chain
PC2
(PC3)
PC3
Diabetes mellitus contd…….

18. Insulin contd…….
 Insulin is measured in IU
FACTORS CONTROLLING THE
SECRETION OF INSULIN
 Blood glucose concentration
 Hormonal control
 Neural control

19. Ca2+
Insulin granules
Na+
Na+
K+
K+
K+
K+
ATP
Na+
K+
-
K+
Glucose
GLUT2
Ca2+
Ca2+
Ca2+
Voltage-gated
Ca2+
channel
KIR
Vm
Pancreatic
ß cell IP3
cAMP
Glucokinase
Km= 7-9 mM
β cell integrates input from
various metabolites, hormones
and neurotransmitters
Diabetes mellitus contd…….

20. Glucose stimulated insulin secretion
β cells respond to blood glucose
concentration in 2 ways: Initial rapid phase &
delayed release phase

21. Neuronal control of insulin secretion
Parasympathetic nervous system:
~stimulates insulin secretion
Sympathetic nervous system:
~inhibits insulin secretion

22. EFFECTS OF INSULIN
ADIPOSE TISSUE
Increased glucose entry
Inhibits lipolysis & release of ffa
Increased triglyceride deposition
Increased K+
uptake
MUSCLE
Increased glucose entry
Increased glycogen synthesis
↑ed aa uptake & protein synthesis
Increased K+
uptake

23. LIVER
↑ed glucose uptake & glycogen
synthesis
Inhibits glycogenolysis &
glucose output
Inhibits gluconeogenesis
GENERAL
Increased cell growth

24. Cell-surface receptors:
α subunits contain
insulin binding sites
β subunits have tyrosine
kinase activity
plasma membraneplasma membrane
Diabetes mellitus contd…….

25.  MOA contd…
 Insulin binds to alpha subunit of receptor
tyrosine kinase (RTK) present in cell
membrane & activates tyrosine kinase
activity of beta subunit.
 There, it is phosphorylated by glucokinase,
which acts as a glucose sensor. The rise in
ATP levels causes a block of K+ channels,
leading to membrane depolarization and an
influx of Ca2+. The increase in intracellular
Ca2+ causes insulin release.

26. PHARMACOKINETICS
 NOT given orally, given s.c.
 Metabolised in liver, kidney & muscle
 Enzymatic degradation follows
receptor-mediated endocytosis
 t1/2 3-5 min

27. TYPES OF INSULIN
ACCORDING TO SOURCE
Conventional Insulin:
a)Bovine (More antigenic)
b)Porcine (Less antigenic)
Highly Purified Insulin Preparation
Human insulin:
Produced by rDNA technology
More water soluble & hydrophobic than
conventional insulin
More rapid s.c. absorption & shorter acting than
conventional insulin
Valuable in case of allergy to conventional,
insulin resistance, lipodystrophy, pregnancy

28. ACCORDING TO ONSET & DURATION
OF ACTION:
Rapid acting:
Insulin lispro, Insulin aspart, Insulin
glulisine
Short acting:
Regular (soluble) Insulin
Intermediate acting:
Insulin Zinc suspension (Lente)
Neutral protamine hagedorn (NPH) or
isophane insulin
Long acting:
Protamine zinc insulin (PZI)
Insulin glargine

29. Rapid acting: insulin lispro
lysine [B28], proline [B29]
Given immediately before or after meal
LYS
PROLYS
PRO
InsulinlisproInsulin

30. Insulin glargine
 Soluble in acidic pH of vial 4.0
 Precipitate in neutral pH & slowly enter into
circulation
 Delayed but peakless effect is obtained
ARG
ARG
ASNGLY
Insulinglargine

31.  Hypoglycemia
 Frequent & potentially more serious
 Common in DM patient receiving large dose
of insulin, missing meals and vigorous
exercise after insulin
 Symptoms: 1) Sympathetic stimulation
2) Neuroglucopenic symptoms
 Treatment: oral/ iv (severe case) Glucose or
Glucagon or Adrenaline treatment
 Local reactions: swelling, erythema ,
Lipodystropy (Common in conventional insulin)
 Allergy & resistance to insulin (esp. conventional)
 Insulin edema- transient on starting insulin
 Weight gain

32.  Type 1 DM:
 Dose is individualized: sliding scale
 2/3 of dose in morning & 1/3 in evening
 Special cases of Type 2 DM:
Failure of oral antidiabetic drugs
Underweight patient
During infection, trauma, surgery
Pregnancy (human insulin)
During complications of diabetes
mellitus
 Non diabetic use: Glucose + insulin to treat
hyperkalemia

33. Mix regimen Bolus regimen
Regular insulin with
lente or isophane
(30:70 or 50:50)
Long acting insulin (Insulin
glargine) and short acting
insulin (lispro/aspart)
injected separately
Injected Before
Breakfast and Before
Dinner
Long acting insulin (glargine)
injected daily (before
breakfast/ before bed time)
with 2-3 meal time injections
with rapid acting insulin
(lispro/aspart)

34. 1. β blocker (nonspecific) are contracted in
Diabetic patient receiving insulin?
 Because β blockers mask the symptoms of
hypoglycemia and also
 Delays recovery-prolong hypoglycemic attack
2. Thiazide, furosemide, corticosteroids,
Oral contraceptives, Salbutamol – reduce
effectiveness
3. Acute ingestion of alcohol-
hypoglycemia