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Diabetes in Pets

Humalog

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Insulin hex di mon

Insulin hexamers (as produced by the body or injected) must break down into dimers and monomers to be absorbed[1].

Humalog is an Eli Lilly fast-acting analog insulin also known as insulin lispro[2]. 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[3].


Aspartlisprotap

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

Figure2

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)[4]. 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[5]. Humalog degrades rapidly--it can be working well one day but not the next[6].

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[7].

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[8].



Amino Acid Sequence of Insulin Preparations[9]
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




<center>Pharmacokinetics of Insulin Preparations[10]
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[11]
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[12]
6
14 to 18
18 to 24
PZI[13]
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 ReadingEdit

Wikidog3


ReferencesEdit

  1. Insulin Dependent Diabetes-Dr. Ragnar Hanas-1999 (Page 5)
  2. Humalog-Insulin Lispro Remedyfind.com
  3. Clinchem.org-Alterations to Human Insulin Producing Insulins Lispro, Aspart & Glargine
  4. EMEA Scientific Discussion-Insulin Lispro-Humalog-Page 1
  5. Diabetesnet.com-Humalog and Heat
  6. Diabetesnet.com-Humalog & Novolog
  7. Selecting an Insulin for Treating Diabetes Mellitus in Dogs & Cats-Page 39
  8. US-FDA Humalog Pharmacology Review-Pages 5 & 6
  9. Pharmacy Times-Guide to Insulin Preparations
  10. Pharmacy Times-Guide to Insulin Preparations
  11. Endotext.com-Insulin Pharmacology
  12. Endotext.com-Insulin Pharmacology
  13. NetDoctor-UK Hypurin Protamine Zinc

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