Humalog

Insulin hexamers (as produced by the body or injected) must break down into dimers and monomers to be absorbed.

Humalog is an Eli Lilly fast-acting analog insulin also known as insulin lispro. Insulin lispro has been altered from the human insulin molecule at positions #28 and #29 on the B insulin chain. The normal amino acids present at B-#28 and B-#29 are Proline (#B-28) and Lysine (B-#29); insulin lispro reverses this so that Lysine is found at B-#28 and Proline at B-#29.

Human time activity profile for insulins lispro (Humalog) and aspart (Novolog/NovoRapid).

Alterations to human insulin structure producing insulins lispro (Humalog) and aspart (NovoRapid/Novolog).

Inverting the normal Proline-Lysine sequence of human insulin at positions #28 & #29 on the B insulin chain created an analog insulin which has less tendency to form into hexamers (self-association). Keeping the insulin from forming hexamers means that in dimer and monomer form, they are able to be absorbed faster and that means more rapid onset, peak and less duration.

Insulin lispro has been known to "wilt" easily when not constantly refrigerated. Those who have had bad vials report finding hazy or small particles on inspection. Humalog degrades rapidly--it can be working well one day but not the next.

Dr. Nelson of University of California-Davis said in his lecture at the Ohio State Endocrinology Symposium in 2006 that if the short-acting analog insulins have any role in feline and canine diabetes, it is not yet determined.

A study of dogs from 1993-1994 using various fractions of Humalog mixes against human NPH/isophane insulin found only minor differences in the use of Humalog Mix as opposed to NPH/isophane insulin.

Amino Acid Sequence of Insulin Preparations
Amino Acid Substitutions
	A-Chain Position			B-Chain Position
Source Species	A-8	A-10	A-21	B-28	B-29	B-30	B-31 B-32
Beef	Ala	Val	Asn	Pro	Lys	Ala	N/A
Pork	Thr	Ilc	Asn	Pro	Lys	Ala	N/A
Human	Thr	Ilc	Asn	Pro	Lys	Thr	N/A
Aspart	Thr	Ilc	Asn	Aspartic Acid	Lys	Thr	N/A
Lispro	Thr	Ilc	Asn	Lys	Pro	Thr	N/A
Glulisine	Thr	Ilc	Asn	Pro	Glu	Thr	N/A
Lantus (glargine)	Thr	Ilc	Gly	Pro	Lys	Thr	Arg
Levemir(detemir)	Thr	Ilc	Asn	Pro	Lys	N/A	Myristic Acid
Ala=Alanine Val=Valine Asn=Asparagine Pro-Proline Lys=Lysine Thr=Threonine Ilc=Isoleucine Glu-Glutamine Gly=Glycine

Pharmacokinetics of Insulin Preparations

Insulin Preparations

Onset (hr)

Peak (hr)

Duration (hr)

Rapid-Acting

R/Neutral

0.5 to 1

2.5 to 5

8 to 12

Lispro

0.25 to 0.5

0.5 to 1.5

2 to 5

Aspart

0.17 to 0.33

1 to 3

3 to 5

Glulisine

0.17 to 0.33

1 to 3

3 to 5

Intermediate-Acting

NPH Isophane

1 to 1.5

6 to 14

16 to 24

Lente

1 to 3

6 to 14

20+

70/30-30/70

0.5 to 1

2 to 12

24

50/50

0.5 to 1

2 to 12

24

Novolog 70/30 Mix

0.25

1 to 3

24

Humalog 75/25 Mix

0.25

0.5 to 1.5

24

Long-Acting

Ultralente

6

14 to 18

18 to 24

PZI

4 to 6

14 to 18

24 to 36

Glargine

1.1

N/A

24

Detemir

0.8 to 2

N/A

up to 24

These are human activity profiles.

Further Reading

• Wiki case--Canine Humalog user