Insulin and Hypoglycaemic Agents

ENDOCRINE SYSTEM: INSULIN AND
ORAL HYPOGLYCAEMIC AGENTS

Blood Glucose
Normal blood glucose concentration 80
100mg/dl.
200mg/dl and above blood glucose
diagnosed as diabetic or 126mg/dl after
an 8hr fast.
1
ENDOCRINE SYSTEM: INSULIN AND ORAL

HYPOGLYCAEMIC AGENTS
Therefore important to control blood sugar

levels.
CNS and red blood cells almost entirely
dependent on glucose as source of energy.
Hypoglycaemia causes
Insufficient energy
Dizziness
Drowsiness and coma
2

Hyperglycaemia causes
Osmotic loss of cell water
Dehydration
Many body tissue malfunction
Hyperosmolar coma
ENDOCRINE SYSTEM: INSULIN

AND ORAL HYPOGLYCAEMIC AGENTS
DIABETES MELLITUS (DM)
Is a chronic metabolic disorder, resulting from
Insulin deficiency.
Is characterised by:
Hyperglycaemia
Altered metabolism of carbohydrates,

proteins, and lipids.
Increased risk of vascular complications
4

The insulin deficiency may be absolute or
relative.
The metabolic abnormalities in diabetes lead to
classic symptoms:
polyuria (frequent micturition)
polydipsia ( excessive thirst)
polyphagia ( excessive hunger)
fatigue
5

Long-term complications include:
Gangrene
Proliferative retinopathy
Myocardial infarction
Polyneuropathy
Uraemia
Renal failure
6

Predisposition to DM is hereditary.
The types of DM.
(i) Insulin dependent (Type I or juvenile onset
IDDM)
-
Usually occurs in non-obese persons before

age of 30 years.
Circulating insulin is virtually absent and betacells fail to respond to stimuli to release insulin.
It is an autoimmune disease of the beta-cells.

7

(ii) Non-insulin dependent (Type II or maturity
onset NIDDM).
Usually occurs after the age of 40 years.
Obesity is a major factor.
The beta-cell mass is moderately reduced.

8

Gestational diabetes refers to the
onset of glucose intolerance in women
during pregnancy (excluding women who
were diabetic before pregnancy).

All forms of DM are due to either:
a decrease in circulating free insulin (insulin
deficiency), or
decrease in response of peripheral tissues to
insulin (insulin resistance) .
- overactivity of insulin antagonistic hormones
like growth hormone, cortisol or
catecholamines may also be involved.
10

Insulin secretion
Insulin is synthesised in the endoplasmic
reticulum and stored in -cells via membrane
transporter Glut 2. Its release involves a
complex interplay between;
Food products
Hormones
GIT hormones
Neural stimuli from ANS and CNS.
11

Factors affecting insulin release
Stimulation of release
Inhibition of release
Glucose
Catecholamines
Exogenous insulin
Starvation
Diazoxide
Phenytoin
Potassium deficiency
Vagotomy
Sulphonylureas
c-AMP
Leucine
ACTH and corticosteroids
Secretin and Pancrozymin
Vagal stimulation
Acetylcholine
Glucagon
12

The most important factor controlling insulin
secretion is glucose.
Increase in blood glucose level promotes both
synthesis and secretion of insulin from beta cells.
The beta-cells have an adenyl cyclase system
which is stimulated by:
glucose or beta-adrenergic stimulation and
inhibited by alpha-adrenergic stimulation
13

Therefore when glucose concentration

rises ATP production increases, K+
channels close and depolarization of the
cells results, and Ca+++ channels open
leading to increased insulin secretion and
release.
14

Elevated insulin blood levels (e g obesity)
decrease number of insulin receptors on
cell membranes (downregulation).
While a fall in insulin blood levels (e g.
diabetes) increases the number of insulin
receptors (upregulation).
15

Insulin is released in 2 phases:

1. Rapid phase release of stored insulin.
2. Delayed phase continued release of stored
insulin and new synthesis of insulin.
It is released as preproinsulin and converted

to preinsulin and then insulin .
16

Metabolism and Excretion
Orally insulin is rapidly proteolysed in the gut.
Has to be given parenterally, usually by SC
injection.
The rate of absorption from site depends on type
of insulin used.
Is rapidly taken by the liver and kidney where it
is mainly degraded
17

In the liver the molecule is broken down by
enzyme glutathione insulin
transhydrogenase (insulinase).
Only metabolites are excreted in urine and
faeces.
Half-life of crystalline insulin is about 40
mins.
18

Actions
In DM there are disturbances in the metabolism
of carbohydrates, fat, protein, electrolytes
and water.
(a) Carbohydrates metabolism:
Insulin deficiency produces two
fundamental defects:
(i) reduced entry of glucose into cells
(ii) increased release of glucose from the
liver into circulation.
19

Leads to:
hyperglycaemia
glycosuria
In addition insulin deficiency leads to
gluconeogenesis (protein to glucose).
Insulin administration stimulates:
(i) entry of glucose and other sugars into cell.
20

(ii) the phosphorylation of glucose and
glycogen synthesis and its storage in the

liver.
(iii) conversion of glucose to triglycerides and

its storage in adipose tissue.
Further insulin inhibits glycogenolysis and
gluconeogenesis.
The above actions result in a fall in the glucose
content of the blood and tissues.
21

(b) Fat Metabolism
Insulin deficiency leads to a mobilization of fat from
adipose tissue into the blood stream (lipaemia).
The blood concentration of triglycerides and FFA rise,
due to increased synthesis in adipose tissue.
The greater availability of FFA to the liver leads to
increased production of acetone acetate and betahydroxybutyric acid (acidosis) and acetone (a ketone).
22

The ketone bodies enter the blood and
produce metabolic ketoacidosis.
The blood cholesterol also rises.
Insulin administration stimulates:
lipogenesis and facilitates the deposition of
triglycerides in adipose tissue.
23

(c) Protein Metabolism
Insulin deficiency and a disordered glucose utilisation
results in:
- impaired protein synthesis.
- increased protein breakdown to amino
acids .
- increased glucose synthesis from amino acids

The protein depletion together with glucose rich
tissues and body fluids predispose the body to
infection.
24

Insulin replacement has anabolic effect
- accelerates the transfer of aminoacids into cells.
- promotes amino acid incorporation
into protein.
- promotes the action of the growth
hormone on protein synthesis.
25

(d) Electrolytes
Insulin facilitates entry of potassium into cells.
- potassium is important in the regulation of

the membrane potential and enzyme activity.
Insulin also promotes magnesium intracellular
accumulation.
- magnesium is responsible for the
activation of many critical intracellular
26
enzymes.

(e) Water
As a consequence of glycosuria, there is
an extra loss of water from the body
(polyuria).
The above leads to dehydration and
polydipsia (abnormal thirst).
Insulin replacement - due to its overall
effect on metabolisms reverses excessive
water loss.
27
Glucose
Fatty
Acids
Triglycerides
Adipose
tissue
Glycogen
Amino
Acids
Protein
Muscle
Liver
Fatty
Acids
Stimulated by insulin
Increased by feeding
Overview of insulin action
Inhibited by insulin
Increased by fasting and in diabetes
28

Mode of Action
The actions of Insulin are initiated by:
the attachment of the insulin molecule to a
specific insulin receptor on the cell surface.
the insulin-receptor complex interaction is
reversible.
the insulin molecule is not chemically altered.
29

the hormone-receptor complex is then
internalized by an endocytotic mechanism.
the insulin molecule is then metabolised and
the insulin receptor is recycled to the
membrane for reuse.
Once inside the cell, Insulin lowers the c-AMP
content in some tissues by:
30

Inhibiting the adenyl cyclase system
is more marked when c-AMP synthesis is
stimulated by hormones like glucagon and
catecholamines, but basal levels of c-AMP are not
much affected.
Stimulating cyclic nucleotide

phosphodiesterase (enzyme which destroys
c-AMP) activity, thus lowering c-AMP of cells.
31

Because of lower c-AMP in cells:
- less glycogen breakdown (glycogenolysis)
occurs.
32

Factors Modifying Insulin Action
The following factors substantially alter the
insulin need in diabetic patients:
(i) Muscular exercise
After exercise the plasma contains a substance
liberated by the skeletal muscle which promotes
oxidation of glucose (can lead to hypoglycaemia,
less insulin needed).
(ii) Factors affecting insulin secretion (as
discussed already)
33

(iii) Insulin antibodies
On repeated injections of insulin specific insulin
antibodies develop in the plasma.
These antibodies bind insulin and it loses its
physiological activity.
Insulin resistance is defined as a state when
daily insulin requirement of an individual
exceeds 200 units.
34

(iv) Insulin antagonists
Such as:
- growth hormone,
- glucocorticoids,
- glucagon, and
- other unidentified materials.
(v) Diet
The diet has to be specially adapted to meet the
metabolic needs, to avoid hyper or
35
hypoglycaemia.

INSULIN preparations
Insulin can be synthesised but is mainly
obtained from cattle or pig pancreas.
They have a biological activity of 25
units/mg.
The pig insulin closely resembles human
insulin (in terms of poly-peptide chains),
36
as a result has low antigenicity.

Insulin is soluble in water, but undergoes
molecular aggregation at pH 3.2 10
(increased by presence of Zn, which
causes insulin crystallisation)
Can be combined with proteins like globin
and protamine to prolong its action.
37

Human Insulin has been successfully

produced:
through E. coli recombinant DNA
technique or
by chemical modification of pig insulin to
replace lone amino acid different from
human insulin.
38

Commercial insulin is a mixture of the

hormone extracted from the pancreas of
cattle (bovine) and pig (porcine).
The potency of insulin is assayed by:
comparing the new sample with an
international standard for its hypoglycaemic
effect,
39

Is measured in groups of mice,
the end point being hypoglycaemic coma.
The potency is measured in units.
Preparations are adjusted to contain 40, 80,
100 or 500 units/ml.
40

The various insulin preparations differ mainly

in the rate of absorption from site of SC
injection.
Regular insulin (Crystalline Insulin) is modified
to form suspensions by two procedures:
(i)
Basic protamine is added to acidic insulin to raise

its pH and form a less soluble complex.
(ii) High concentrations of zinc and acetate buffer

make if possible to prepare suspensions having
varying particle size.
41

The above factors determine the time of onset
and duration of action of the preparation.
Therefore insulins are classified according to
the time of onset and duration of action.
42

1. Fast Acting
Preparation
action(hrs)
(i) Regular
Crystalline
insulin
Onset of Duration of
action (hrs)
1
5
(ii) Prompt Insulin
12-16
Zinc Suspension
(SEMILENTE)
43

2. Intermediate Acting
(i) Isophane Insulin
2
Suspension
(NPH Insulin)
(ii) Insulin Zinc
Suspension
(LENTE)
2-4
18-24
(iii) Globin Zinc 1-2
12-18
18-24
Insulin
(Globin Insulin)
44

3. Long Acting
(i) Protamine Zinc
Insulin Suspension
(PZI)
(ii) Extended Zinc
Insulin Suspension
(ULTRALENTE)
4-6
24-36
4-6
24-36
45

Newer Insulins
1. Actrapid (Nusol) recrystallised porcine
insulin, acts faster than regular insulin.
2. Rapitard (Biphasic Insulin) actrapid (1part)
and insoluble crystals of bovine insulin (3 parts),
same action as lente insulin but quicker onset.
3. Monotard is a monocomponent insulin zinc
suspension of highly purified porcine insulin and
is devoid of antigenic property.
46

4. Human Insulins highly purified insulins
prepared by:
recombinant DNA technique in E. coli, or
semisynthetically using porcine insulins starting
material and modifying some amino acids e g lispro
Has more rapid absorption and action after SC injection
than regular insulin.
Should be administered 15mins before meals.
Achieves peak at 30 -120 mins compared to 60 -120
mins regular insulin.
Has shorter duration of action therefore usually used
with longer acting regular insulin.
47

Insulin administration
(i) Insulin syringe a syringe graduated into
units of insulin. Injected through the SC route.
(ii) Open loop system- uses a micro computer
to regulate the flow of insulin from the syringe to
the needle inserted subcutaneously in diabetic
patient.
48

(iii) Closed loop system automatically

reads blood glucose levels and adjusts the
rate of insulin delivery, subcutaneously.
49

Adverse Reactions and Precautions
1. Hypoglycaemia
May occur due to:
- insulin overdosage
- failure to eat
- unaccustomed physical exercise
- ingestion of alcohol (impairs hepatic
gluconeogenesis).
50

2. Insulin allergy
Occurs infrequently.
Is manifested by local itching and
lymphadenopathy.
Insulins containing proteins are more likely
to cause allergy than lente.
51

3. Insulin lipoatrophy
Atrophy of subcutaneous fat occurs at sites
of frequent insulin injections.
The absorption of insulin from such sites
becomes erratic.
Can be avoided by frequent change of site
of injection.
52

4. Insulin presbyopia
(Difficulty or loss of eye accommodation)
Occurs when a diabetic is rapidly
controlled with insulin.
The condition gradually settles down.
53

5. Insulin neuropathy
Rapid control of diabetes with insulin may
precipitate or worsen pre-existing neuropathy.
6. Insulin resistance
On prolonged insulin administration the daily
requirement gradually rises due to formation of
insulin antibodies.
Insulin resistance can be managed by
administering glucocorticoids (prednisolone); or
change over from bovine to porcine insulin.
54

7. Obesity
Insulin therapy without dietary restriction
can lead to obesity.
55

Therapeutic uses
1. In diabetes mellitus
2.In schizophrenia
Insulin shock therapy, is a useful therapeutic
measure.
The coma is allowed to last 20-30 minutes, then
terminated by administration of glucose by IV or
stomach tube, glucagon can also be used to
terminate coma.
56

3. Myocardial infarction
Insulin, glucose and potassium have been used
with benefit.
4. Anorexia nervosa
Insulin improves appetite and there is
simultaneous gain in body weight.
5. Burns
Insulin with glucose administration reduces the
nitrogen and potassium losses in severely burnt
patients.
57

Indications for Insulin Therapy in DM
All diabetics do not require insulin.
Some patients of the maturity-onset type can be
controlled on diet and exercise alone.
The following categories necessarily require
insulin administration.
(i) Juvenile diabetics, especially of more than 2
years duration.
58

(ii)
Older diabetics with maturity-onset

diabetes.
(iii) All diabetics with complications.
(iv) Diabetic coma and precoma
(v) Primary and secondary failure of
sulphonylurea therapy.
(vi) During pregnancy to avoid the
possible embryopathic activity of oral
hypoglycaemic agents.
(vii) Diabetics undergoing surgery.
59

GLUCAGON
Is synthesised, stored and secreted by alpha
cells of Islets of Langerhans.
Glucose is major regulator of glucagon secretion.
Hyperglycaemia inhibits, while hypoglycaemia
stimulates release of glucagon.
Thus glucose is a major glucagon inhibitor.
60

Secretion of glucagon is also regulated by
the ANS innervation of the pancreatic Islet.
Stimulation of sympathetic nerves or
administration of sympathomimetic amines
increases glucagon secretion.
61

Mode of action
Glucagon promotes glucose production
(glycogenolysis) from liver glycogen via:
stimulation of the adenyl cyclase cell wall system,
formation of c-AMP (which mediates effect of
glucagon on liver), and
activation of hepatic phosphorylase (a rate limiting
enzyme in glycogenolysis)
62

Glucagon also:
increases hepatic gluconeogenesis and
ketogenesis
stimulates protein catabolism.
stimulates release of catecholamines from the
adrenal medulla.
Increases contractility of the myocardium,
causing a rise in blood pressure.
63

Therapeutic Uses
1. Insulin hypoglycaemia, to raise levels of
glucose.
2. Used with dextrose to cut short insulin
induced hypoglycaemia coma.
3. In diagnosis of Insulinomas (glucagon
elevates glucose blood sugar).
4. In diagnosis of the hepatic form of
glycogen storage disease (glucagon
fails to elevate blood glucose levels).
64

5. May be used in treatment of beta-blocker
(propranolol) poisoning (its effect on
myocardium), increases c-AMP production.
Adverse reactions: nausea after large doses
and hypersensitivity reactions may occur.
Dose: Glucagon hydrochloride 1 mg IM, IV.
65

ORAL HYPOGLYGLYCAEMIC AGENTS
Oral hypoglycaemic agents are divided into two
classes:
(i) Sulphonylureas
(ii) Biguanides
66

Drug and Class Duration Tablet
Dose
of action strength
range (g)
(hours)
(mg)
(daily)
Sulphonylureas
Tolbutamide
6-12
250, 500 0.5-3.0
Acetaohexamide 12-14
250, 500 0.25-1.5
Tolazamide10-14
100, 250 0.1-1.0
Chlorpropamide 48-60
100, 250,
500
0.1-0.5
Glibenclamide 10-15
5
5-40
Glipizide
24
5, 10
5-40
67

Drug and Class
Duration
of action
(hours)
Tablet Dose
strength
range (g)
(mg)
(daily)
Glyburide
24
1.25, 2.5, 2.5-20

5
4-6
25
50-200
8-14
5-6
50
500
50-200
1-1.5
Biguanides
Phenformin
Phenformin Timed
Metformin
68

Sulphonylureas
They are chemically related to the
sulphonamides but have no antibacterial activity.
Pharmacological Actions
Are readily absorbed from GIT, partially protein
bound and metabolised in the liver.
They lower blood glucose level in non-diabetic
and Type II diabetes.
69

Simultaneously they lower the plasma free
fatty acid levels.
They are only effective in the presence of
a functioning pancreas.
They normalise the metabolic status of the
diabetic.
Like Insulin patients tend to gain weight.
70

Mode of Action
(1)The sulphonylureas stimulate the beta-cell islet
tissue to secrete insulin (islet betacytotropic
activity).
They block the ATP dependent K+ channels
thereby depolarising the membrane and causing
release of insulin, thus
they cause degranulation of the beta-cells.
(2)They also inhibit hepatic glycogenolysis.
71

(3) They increase binding of Insulin to

target tissues and receptors.
They are ineffective in Type I diabetes
because the pancreas loses its
capacity to synthesize and secrete
insulin
72

Toxicity
Toxicity is remarkably low in properly managed
patients, but the following reactions have been
observed.
(i) Hypoglycaemia
- Due to overdose, missed meals, vomiting or
associated liver and kidney damage.
- Alcohol may induce severe hypoglycaemia.
73

(ii) Allergic skin reactions
(iii) Bone marrow depression (leucopenia,
thrombocytopenia and agranulocytosis may
occur).
(iv) Chlorpropamide is reported to induce
jaundice.
74

(v) There is likelihood to induce
embriyopathy.
(vi) They are goitrogenic as they inhibit the
iodide uptake by the thyroid gland.
(vii) Chlorpropamide may induce severe
intolerance to alcohol.
75

Therapeutic Uses
(i) Maturity-onset diabetes mellitus, in patients
who cannot be controlled on diet alone.
Criteria for selection is:
(a) Obese subjects, aged 40 or more.
(b) Diabetics of less than 10 years
duration, without significant ketonuria or
other acute complication.
76

(c) Fasting blood glucose level less than
300mg/dl.
(d) Regular insulin requirement less than 40
units per day.
(e) Absence of acute renal disease.
77

70% of patients respond, the rest fail to
respond, primary failures.
Out of the 70% who respond earlier, on
prolonged therapy, the response gradually
diminishes due to progressive deterioration of
pancreatic function secondary failures
78

(ii) Insulin-resistant diabetes mellitus
(iii) Chlorpropamide has been used in
some cases of diabetes insipidus
(ADH deficient condition)(vasopressin
potentiation).
79

Biguanides
Differ from the sulphonylureas in their action.
Do not lower blood glucose levels in nondiabetic persons.
Lower blood glucose in diabetics and in absence
of a functioning pancreas.
80

Thus lower blood glucose in both types of
diabetes mellitus.
They potentiate the hypoglycaemic action
of insulin and sulphonylureas.
They also reduce hyperlipidaemia (LDL
and VLDL) and HDL rises.
81

Mode of Action
Their actions are extrapancreatic.
Do not depend on the presence of
exogenous or endogenous insulin in the
body.
(i) They stimulate the peripheral utilisation
of glucose, such as in muscles.
82

(ii) They decrease hepatic glucose output,
by inhibiting gluconeogenesis.
(iii) They also reduce the intestinal
absorption of glucose.
83

Therapeutic Uses
Metformin
(i) Metformin is used for treatment of maturity-onset
diabetes mellitus according to the criteria for
sulphonylureas.
Is well absorbed orally and not bound to serum
proteins.
Is not metabolised and is excreted via urine.
84

(ii) Metformin may be combined with
sulphonylureas in case of primary or
secondary failure.
(iii) Metformin may be combined with
insulin in the management of juvenile
diabetes to induce smooth hypoglycaemia
and the dose of insulin is reduced
85

Toxicity
Metformin
Induces metallic taste, nausea, anorexia,
and diarrhoea.
Causes lethargy, muscle weakness, and
weight loss.
May cause ketonuria and lactic acidosis.
86

Newer Oral Hypoglycaemic Agents
1.Thiazolidinedione Derivatives
Is a new class of oral antidiabetics, it
includes Troglitazone, Ciglitazone,
Englitazone, Poiglitazone.
They work by :
(i) enhancing the target tissue sensitivity to
insulin.
87

(ii) They potentiate the action of insulin by
increasing glucose uptake and glucose
oxidation both in the muscle and adipose
tissue.
(iii) They also reduce hepatic glucose output and
lipid synthesis in muscle and adipose tissue.
The effects occur without any increase in insulin
release.
88

Troglitazone is available as 200 and
400mg tablets.
Dosage is standardised according to the
patient.
89

2. alpha-Glucosidase Inhibitor
Acarbose
Is an orally active drug for NIDDM.
It is a possible adjunct to Insulin in IDDM
patients.
Works by inhibiting alpha-glucosidase enzyme
in the intestinal brush border and thus
decreases the absorption of starch and
disaccharides.
90

Consequently the rise of blood sugar is blunted.
Does not stimulate insulin release from

pancreas or increase insulin action in the
tissues.
Thus Acarbose does not cause hypoglycaemia.
Can be used alone or in combination with other
oral hypoglycaemic agents.
91

It is poorly absorbed.
Major side effects are: flatulence,
diarrhoea, and abdominal cramps.
Dose: Initially 50mg OD during first week,
50mg bid second week, 50mg tid third
week, further increments made after 4-8
weeks to 200mg max.
92

Insulin and Hypoglycaemic Agents

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ENDOCRINE SYSTEM: INSULIN AND

ORAL HYPOGLYCAEMIC AGENTS

ENDOCRINE SYSTEM: INSULIN AND ORAL

Therefore important to control blood sugar

ENDOCRINE SYSTEM: INSULIN AND ORAL

ENDOCRINE SYSTEM: INSULIN

Altered metabolism of carbohydrates,

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

Usually occurs in non-obese persons before

It is an autoimmune disease of the beta-cells.

ENDOCRINE SYSTEM: INSULIN

Obesity is a major factor.

The beta-cell mass is moderately reduced.

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN AND ORAL

Therefore when glucose concentration

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN AND ORAL

Insulin is released in 2 phases:

It is released as preproinsulin and converted

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

glycogen synthesis and its storage in the

(iii) conversion of glucose to triglycerides and

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

- increased glucose synthesis from amino acids

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

- potassium is important in the regulation of

ENDOCRINE SYSTEM: INSULIN

Overview of insulin action

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

Stimulating cyclic nucleotide

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN AND ORAL

Human Insulin has been successfully

ENDOCRINE SYSTEM: INSULIN AND ORAL

Commercial insulin is a mixture of the

ENDOCRINE SYSTEM: INSULIN

ENDOCRINE SYSTEM: INSULIN

The various insulin preparations differ mainly

Basic protamine is added to acidic insulin to raise

(ii) High concentrations of zinc and acetate buffer

ENDOCRINE SYSTEM: INSULIN