Pharmacodynamic Glycemia Effects from Rapid and Long-Acting Insulins Administered at Mealtime to Alloxan-Induced Diabetic Miniature Yucatan Swine

Authors

Brown, L.D., Madsen, T.J., Blair, E.C., Hanks, B.C., Horlen, K.P., Hiemstra, J., Stricker-Krongrad, A., Liu, J., Bouchard, G.F.

Abstract

Pharmacodynamic effects on glycemia from various marketed insulins with known properties in humans were studied in the Yucatan miniature swine for comparative purposes. Yucatan miniature swine (Susscrofa, at least 3 months, 20-60 kg) were made diabetic with intravenous alloxan and regulated on insulin. Animals were considered diabetic if they became hyperglycemic (≥150 mg/dL) within 2-5 days following induction. All procedures were on overnight fasted animals (no feed or insulin for 18 hrs). A recent survey of our diabetic miniswine revealed an average baseline bGof 429 mg/dL±84.5 (SD) (N=148 measurements) while non-diabetics averaged 58.7 mg/dL(N=26). For this study, well-known prototypical marketed insulins (Humalog™, Apidra™, Lantus™; 0.25 or 0.45 U/kg s.c.) were administered at mealtime, then blood glucose profiles recorded using handheld glucometerdevices (One Touch Ultra®, Lifescan) over the next 8 hrs (rapid-acting) or 24 hrs (long-acting). Venous blood samples were collected from VAPs for these bG readings. Blood glucose profile data in the diabetic Yucatan generally compared well to published human glucodynamic data for effect onset and peak effect but not duration for the rapid-acting insulinstested. These data suggest the Yucatan diabetic model under these conditions has similar pharmacodynamic responses to the presentation of exogenous insulins for onset and peak effects but not necessarily duration for the rapid-acting insulins. The long-acting insulin also peaked in swine where no peak (same action throughout day) is normally reported in humans. These differences could be due to either the duration of the fasting, the relative high doses of insulin, and the use of a small number of animals in this study.

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