EXPERIMENT 10:

INSULIN-INDUCED
CONVULSIONS
Albao. Caracas. Edquiban. Gatlabayan.
Revilleza

INTRODUCTION
INSULIN
peptide hormone made by the beta cells of the pancreas that
allows the body to utilize glucose from carbohydrates in food to become
an energy source or to store for future use (lipogenesis, glycogenesis)
secreted when blood glucose level is high
promotes absorption of glucone in fat, liver and skeletal muscles
keeps blood sugar level in normal range

INTRODUCTION
DIABETES
the most common problem associated with insulin
occurs when body does not secrete enough insulin or when the
body cant use the insulin secreted in the body effectively

INTRODUCTION
TYPE 1 DIABETES
pancreas cannot produce enough insulin to meet the bodys needs
common in children
SIGNS:
tiredness, increased urination and thirst, and problems with
vision

INTRODUCTION
TYPE 2 DIABETES
common with adults
associated with lifestyle
there is insulin production but the body cant use it effectively

MATERIALS
Distilled H20
50% sterile glucose soln.
4 adult laboratory mice (same sex and weight).
Regular insulin
Tuberculin syringe
Gavage needle
Epinephrine
Glucometer

METHODOLOGY
Each of the 4 mice were labeled
with letters A, B, C, and D.

Two out of the four mice were fasted for

24hrs, while an ad libitum supply of water
was still provided for all subjects.

Blood was collected from the tail vein and

was subsequently measured for glucose
levels.

4 units of insulin were

injected to the mice.

The time of the resolution of tremors and

convulsions (due to glucose/epinephrine
administration) was recorded for each
mouse.

As soon as the tremors appeared, blood

collected from the tail vein was again
measured for glucose levels and either 50%
glucose solution or epinephrine were
administered to the mice post-collection.
Tremors and convulsions were carefully
noted/documented.

Changes in the respiratory rate and

behavior of each of the 4 mice were then
observed. Particular notice was given to the
onset of tremors and convulsions.

METHODOLOGY
GLYCEMIC
STATE
Fasted

Fasted

Non-Fasted

Non- Fasted

ANIMAL
Mouse A

TREATMENT
1

TREATMENT
2

Insulin(4
units)

Epinephrine
IV 0.10 ml

Mouse B

Insulin(4
units)

Mouse C

Insulin(4
units)

Epinephrine
IV 0.10 ml

Mouse D

Insulin(4
units)

0.10 ml
Glucose
(gavage)

Glucose
(gavage)

RESULTS
Table 1. Observed changes in RR after SC injection of Insulin

Animal

RR before insulin
injection

RR after insulin
injection

134

112

116

108

136

136

136

120

RESULTS
Table 2. Blood glucose level (mmol/L) after SC injection of Insulin

Animal

Just before
insulin injection

Time when
tremors and
convulsions was
observed (Ideal)

Time when
tremors and
convulsions
ceased after
admn of
treatment (Ideal)

2.9 mmol/L

Decrease

Increase

5.8 mmol/L

Decrease

Increase

6.7 mmol/L

Decrease

Increase

5.9 mmol/L

Decrease

Increase

RESULTS
Table 3. Time when tremors and convulsions observed and time when tremors and
convulsions ceased after admn of treatment
Animal
Start time
Time when
Time when
tremors and
tremors and
convulsions was
convulsions
observed
ceased after admn
of treatment
A

50 min

Did not cease

38 sec

73 min 35 sec

93 min

1 min 23 sec

59 min 12 sec

Did not cease

1 min 57 sec

45 min 33 sec

60 min

DISCUSSION
1.

Mechanism of insulin in correlation with BGL in inducing tremors and

convulsions

2.

Metabolic adjustments after insulin injection, glucose, and EP

administration

3.

Metabolic adjustments after insulin injection, then glucose

administration

4.

Metabolic adjustments after insulin injection, then EP administration

INSULIN AND CONVULSIONS

Involved in the metabolic pathways of carbohydrates, fats, and
proteins

PROMOTE: glucose utilization, glycogenesis in

skeletal muscles and liver, protein anabolism, and
growth development by cellular proliferation
INHIBIT: glycolysis, lipolysis, and protein catabolism
More anabolic
TWO MAIN MOAs:

1. Lower blood concentrations of glucose, fatty acids

and amino acids
2. Promote intracellular conversion of the compounds
into their storage forms (glycogen, triglycerides,
proteins)

INSULIN AND CONVULSIONS

Secretion of insulin is by positive feedback mechanism
In the experiment:
NON FASTED: High glucose in the body = stored as either glycogen
or fats
FASTED: Glucose will be utilized immediately = faster causation of
convulsions (not enough glucose)

INSULIN AND CONVULSIONS

INSULIN AND CONVULSIONS

1.

Insulin binds to insulin-receptors on cells

2.

Expression of glucose transfer proteins (GLUT) in order to

facilitate glucose translocation into the cells

3.

Once there is cellular uptake of glucose, it is utilized by

the cells of the body as an energy source by undergoing
glycolysis and entering the Krebs Cycle to form ATPs

4.

Hydrolysis of ATP is required for maintaining the Na-KATPase pump

INSULIN AND CONVULSIONS

5.

Absence of glucose would mean depreciation in the amount of ATPs

. The voltage-gated channels of sodium and potassium to remain
open
. Increase in influx of sodium and potassium ions would occur
. Leads to cellular depolarization, causing muscle tremors and
convulsions

INSULIN AND CONVULSIONS

Since glucose is the only source of energy of the CNS, hypoglycemia
can cause nervousness, weakness, dizziness, tremors, convulsion, or
even death

INSULIN AND CONVULSIONS

Inside the brain
1.

Na+ ions would leak out of the cells to be replaced by K+ ions

2.

Negative charge maintained inside the neurons is lost during

hypoglycemia, leading to uncontrolled depolarization and opening
of voltage-gated channels

INSULIN AND CONVULSIONS

3.

The disruptions on the brains ionic gradient may cause:

. uncontrolled firing of electric impulses from the nerve axons to
peripheral neurons
. inability of depolarized neurons to hyperpolarize again due to
the lack of ATP substrate

INSULIN AND CONVULSIONS

4.

This massive neuronal disruption eventually causes tremors and

convulsions, also known as Gal mal seizures, caused by
hypoglycemia

5.

Further accumulation of Na+ in the interstitium may attract water

molecules from the circulation causing cerebral edema which may
result to hypoxia, coma and eventually death

INSULIN, GLUCOSE, AND

EPINEPHRINE
Metabolic adjustments (insulin)

Liver

Glucose output
1. Gylcogenesis
2. Gluconeogenesis
3. Glycolysis

D
I
D
I

Lipogenesis

Ketoacids

Proteogenesis

INSULIN, GLUCOSE, AND

EPINEPHRINE
Metabolic adjustments (insulin)

Muscles

Glucose uptake

Glycolysis

Glycogenesis

Amino acid uptake

Proteogenesis

Ketoacid uptake

Fatty acid uptake

K+ uptake

INSULIN, GLUCOSE, AND

EPINEPHRINE
Metabolic adjustments (insulin)

Adipose tissue

Glucose uptake

Glycolysis

Synthesis of FA

Synthesis of
glycerol-phosphate

Lipogenesis

Inhibition of lipase

K+ uptake

INSULIN, GLUCOSE, AND

EPINEPHRINE
Metabolic adjustments (insulin)

Concentrations
in the blood

Glucose

Amino acids

Fatty acids

Ketoacids

K+

INSULIN, GLUCOSE, AND

EPINEPHRINE
Metabolic adjustment (glucose)
After the administration of glucose, insulin would then
act to increase the permeability of glucose through the
cell membranes
In response to hypoglycemic conditions, the binding of
insulin to its receptors on cells increases cellular uptake
of glucose up to twenty times the normal amount to
correct the deficiency

INSULIN, GLUCOSE, AND

EPINEPHRINE
Metabolic adjustment (epinephrine)
LIVER

2 receptors: glycogenolysis

1 adrenergic receptors: mobilize intracellular Ca2+

PANCREAS

2 receptors: insulin and glucagon release

1 adrenergic receptors: decrease insulin

INSULIN, THEN GLUCOSE

INSULIN:
Low levels of blood glucose circulating around the body
Low energy production of cells
Impairment of the ion pump mechanisms of cell and may affect the
ion transports of the cell
May result to cell damage

INSULIN, THEN GLUCOSE

THEN GLUCOSE:
Relieve the energy production of the cells
Reverse cell damage

INSULIN, THEN EPINEPHRINE

1.

Insulin-induced hypoglycemia

2.

Administration of epinephrine

3.

Glycogenolysis (skeletal muscles and liver) and glucagon release

(pancreas)

4.

Normal blood glucose level

5.

Increased availability of substrate to normalize brain osmolarity and

ion influx

6.

Termination of seizures