Insulin

Question 1

Instability of insulin

Answer 1

Drug instability may be advantageous to certain individuals, e.g., insulin
Numerous accidental insulin overdoses
Prolonged hypoglycemia light threatening
Less frequent agent of suicide in both diabetics and non-diabetics
Insulin used as an instrument of homicide
Rare occurrence
Marks review of the literature found only 66 cases worldwide
Conviction only 31 cases, with the additional weapon used in 11 of the cases

Question 2

Nurse Kenneth Barlow

Answer 2

1st. case of murder facilitated by insulin in england
“You could commit a perfect murder with insulin. It cannot be traced”
Wife was pregnant and neither wanted a baby
Gave her injections to “induce an abortion”
Found “drowned”…
Pathologist noted four injection sites in her buttocks
Excised for analysis
Insulin detected; not a diabetic, thus no need for insulin
Barlow gave wife insulin, instead of abortifacient, to make her stuporous and complaisant
Placed her comatose in the tub – slide under the water and drowned

Question 3

Martha sharp crawford von bulow

Answer 3

Known as Sunny von Bulow
 American heiress, socialite, and philanthropist
o Found in coma
o Husband, Claus von Bulow

 Convicted of attempting murder to her (1980) by insulin overdose
o Second trial found him not guilty
 Experts opined that there was no insulin injection
 Symptoms attributed to over-use of Rx drugs
o Sunny von Bulow lived almost 28 years in a persistent vegetive state until her
death in a New York nursing home on dec 6, 2008

Question 4

proinsulin

Answer 4

o Two peptide chain molecules (insulin) linked by connecting peptide [C-peptide]
o Synthesized by the B-cells of the pancreas

Question 5

what do you see when you increase glucose

Answer 5

Causes a proteolytic cleavage of the proinsulin molecule
o T=yields the active insulin molecule and the inactive c-peptide in a molar ratio
of 1:1

Question 6

C-peptide

Answer 6

 C-peptide is produced simultaneously with insulin in the insulin precursor – proinsulin
 In proinsulin, C-peptide is located as if connection insulin A and B chains
 So, it is called “c(onnecting) peptide”

Question 7

plasma half life

Answer 7

Plasma half-life of insulin is ~5-8 minutes
o Degraded by red-cell proteolytic enzymes, in kidney and liver

Question 8

C-peptide half life

Answer 8

10-20minutes
degraded by kidneys

Question 9

what can happen if patient previously exposed to exogenous insulin

Answer 9

may develop antibodies to insulin
degrade degration
leads to falsely high or low values

Question 10

what is the main difference between endogenous and exogenous insulin

Answer 10

Major difference between commercial insulin and endogenous insulin is the absence of
C-peptide

Question 11

what do you expect with large dose of exogenous insulin

Answer 11

elevated insulin and suppressed C-peptide
o Suppression of C-peptide due to negative feedback system
 Stops cleavage
o Hypoglycemic effect of insulin potentiated by alcohol

Question 12

IS insulin stable

Answer 12

fairly stable at 4C
significant degaration notes at 37V four to five days

Question 13

normal ranges of insulin

Answer 13

serum: 0-22
C-peptide.08-4.6

Question 14

normal fasting regions for insulin

Answer 14

5-75

Question 15

fatal insulin ranges

Answer 15

800-3200

Question 16

what ratio identifies an insulin overdose

Answer 16

molar-ratio od greater than 1l

Question 17

what tubes for insulin

Answer 17

red-top tubes

Question 18

C=peptide degrade?

Answer 18

yes in serum or improperly collected plasma

Question 19

interpretive challenges

Answer 19

High degree of suspicion and rapid/proper sample collection and analysis
 Hemolysis
o Release of proteolytic enzymes will lower insulin and C-peptide concentrations
 Stability
o Instability at elevated temperatures
 Assays may cross-react with insulin antibodies