Diabetes in Pets
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NovoRapid, also known as insulin aspart and Novolog[1], is a Novo Nordisk fast-acting analog insulin.

Technical details

Amino acid alterations of human insulin producing insulins aspart (Novolog/NovoRapid) and lispro (Humalog).

Preventing this self-association keeps the insulin in dimer and monomer form, making them absorb better and faster, resulting in faster onset, peak and less duration.

How insulin aspart differs from human insulin is the change at position #28 in the B insulin chain; the natural amino acid present is Proline--insulin aspart substitutes aspartic acid for it[2] This substitution reduces the tendency of the insulin to form hexamers[3].

Insulin hexamers (as produced by the body or injected) must break down into dimers and monomers to be absorbed[4].

While insulin aspart has rapid-acting characteristics in humans, the insulin does not elicit the same response in dogs[5]. "Neither rat nor dog indicated the faster action of X14 (insulin aspart) or faster sc (subcutaneousabsorption, this could be shown in pigs and later in man." Novo Nordisk's documents discuss the fact that the skin of both dogs and rats contain less lipid (fat) than that of humans and pigs as a possibility for the lack of rapid action in the two species.

A slight increase in alkaline phosphatase (ALP-liver values)[6] was noted in non-diabetic dogs treated with insulin aspart. The same increase was also noted in non-diabetic dogs treated with non-analog human insulin. The significance of this finding was declared unclear. Some humans treated with insulin aspart also presented higher ALP values[7].

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

Both NovoRapid (insulin aspart) and human insulin were tested on cats as part of the FDA-drug approval process. It is acknowledged that cats are sensitive to insulin aspart-the link below details the study[8].

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[9].

Insulin amino acid sequences


Amino Acid Sequence of Insulin Preparations[10]
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

Insulin pharmacokinetics

Pharmacokinetics of Insulin Preparations[11]
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[12]
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[13]
6
14 to 18
18 to 24
PZI[14]
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.

References

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