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Publication
Peripherally delivered hepatopreferential insulin analog insulin-406 mimics the
hypoglycaemia-sparing effect of portal vein human insulin infusion in dogs.
Authors Gregory JM, Kraft G, Scott MF, Neal DW, Farmer B, Smith MS, Hastings JR, Madsen
P, Kjeldsen TB, Hostrup S, Brand CL, Fledelius C, Nishimura E, Cherrington AD
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Diabetes, obesity & metabolism
Year 2019
Date Published 10/1/2019
Volume : Pages 21 : 2294 - 2304
PubMed Reference 31183936
Abstract We previously quantified the hypoglycaemia-sparing effect of portal vs
peripheral human insulin delivery. The current investigation aimed to determine
whether a bioequivalent peripheral vein infusion of a hepatopreferential insulin
analog, insulin-406, could similarly protect against hypoglycaemia., Dogs
received human insulin infusions into either the hepatic portal vein (PoHI, n =
7) or a peripheral vein (PeHI, n = 7) for 180?minutes at four-fold the basal
secretion rate (6.6 pmol/kg/min) in a previous study. Insulin-406 (Pe406, n = 7)
was peripherally infused at 6.0 pmol/kg/min, a rate determined to decrease
plasma glucose by the same amount as with PoHI infusion during the first
60?minutes. Glucagon was fixed at basal concentrations, mimicking the diminished
a-cell response seen in type 1 diabetes., Glucose dropped quickly with PeHI
infusion, reaching 41?±?3 mg/dL at 60?minutes, but more slowly with PoHI and
Pe406 infusion (67?±?2 and 72?±?4 mg/dL, respectively; P?both). The hypoglycaemic nadir (c. 40?mg/dL) occurred at 60?minutes with PeHI
infusion vs 120?minutes with PoHI and Pe406 infusion. ?AUCepinephrine during the
180-minute insulin infusion period was two-fold higher with PeHI infusion
compared with PoHI and Pe406 infusion. Glucose production (mg/kg/min) was least
suppressed with PeHI infusion (? = 0.79?±?0.33) and equally suppressed with PoHI
and Pe406 infusion (? = 1.16?±?0.21 and 1.18?±?0.17, respectively; P = NS). Peak
glucose utilization (mg/kg/min) was highest with PeHI infusion (4.94?±?0.17) and
less with PoHI and Pe406 infusion (3.58?±?0.58 and 3.26?±?0.08, respectively;
P?achieve a metabolic profile that closely mimics portal insulin delivery, which
reduces the risk of hypoglycaemia compared with peripheral insulin infusion.




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