AIMS: 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. MATERIALS AND METHODS: 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 α-cell response seen in type 1 diabetes. RESULTS: 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 < 0.01 vs PeHI for both). The hypoglycaemic nadir (c. 40 mg/dL) occurred at 60 minutes with PeHI infusion vs 120 minutes with PoHI and Pe406 infusion. ΔAUCepinephrine 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 (Δ = 0.79 ± 0.33) and equally suppressed with PoHI and Pe406 infusion (Δ = 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 < 0.05 vs Pe for both). CONCLUSIONS: Peripheral infusion of hepatopreferential insulin can achieve a metabolic profile that closely mimics portal insulin delivery, which reduces the risk of hypoglycaemia compared with peripheral insulin infusion.
AIMS: We previously quantified the hypoglycaemia-sparing effect of portal vs peripheral humaninsulin 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. MATERIALS AND METHODS:Dogs received humaninsulin 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 α-cell response seen in type 1 diabetes. RESULTS: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 < 0.01 vs PeHI for both). The hypoglycaemic nadir (c. 40 mg/dL) occurred at 60 minutes with PeHI infusion vs 120 minutes with PoHI and Pe406 infusion. ΔAUCepinephrine 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 (Δ = 0.79 ± 0.33) and equally suppressed with PoHI and Pe406 infusion (Δ = 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 < 0.05 vs Pe for both). CONCLUSIONS: Peripheral infusion of hepatopreferential insulin can achieve a metabolic profile that closely mimics portal insulin delivery, which reduces the risk of hypoglycaemia compared with peripheral insulin infusion.
Authors: Dale S Edgerton; Sylvain Cardin; Catherine Pan; Doss Neal; Ben Farmer; Margaret Converse; Alan D Cherrington Journal: Diabetes Date: 2002-11 Impact factor: 9.461
Authors: Justin M Gregory; Guillaume Kraft; Melanie F Scott; Doss W Neal; Ben Farmer; Marta S Smith; Jon R Hastings; Eric J Allen; E Patrick Donahue; Noelia Rivera; Jason J Winnick; Dale S Edgerton; Erica Nishimura; Christian Fledelius; Christian L Brand; Alan D Cherrington Journal: Diabetes Date: 2015-06-17 Impact factor: 9.461
Authors: S Mudaliar; R R Henry; T P Ciaraldi; D A Armstrong; P M Burke; J H Pettus; P Garhyan; S L Choi; M P Knadler; E C Q Lam; M J Prince; N Bose; N K Porksen; V P Sinha; H Linnebjerg; S J Jacober Journal: Diabetes Obes Metab Date: 2016-10 Impact factor: 6.577
Authors: Robert R Henry; Sunder Mudaliar; Theodore P Ciaraldi; Debra A Armstrong; Paivi Burke; Jeremy Pettus; Parag Garhyan; Siak Leng Choi; Scott J Jacober; Mary Pat Knadler; Eric Chen Quin Lam; Melvin J Prince; Namrata Bose; Niels Porksen; Vikram P Sinha; Helle Linnebjerg Journal: Diabetes Care Date: 2014-06-19 Impact factor: 19.112
Authors: Dale S Edgerton; Mary C Moore; Jason J Winnick; Melanie Scott; Ben Farmer; Helle Naver; Claus B Jeppesen; Peter Madsen; Thomas B Kjeldsen; Erica Nishimura; Christian L Brand; Alan D Cherrington Journal: Diabetes Date: 2014-06-19 Impact factor: 9.461
Authors: Ruth S Weinstock; Bruce W Bode; Satish K Garg; David C Klonoff; Caroline El Sanadi; W Blair Geho; Douglas B Muchmore; Marc S Penn Journal: Diabetes Obes Metab Date: 2022-05-25 Impact factor: 6.408