Effect of intraportal and peripheral insulin on glucose turnover and recycling in diabetic dogs.

The effects of peripheral and portal intravenous infusions of insulin on hepatic glucose production and glucose recycling have been compared in conscious diabetic dogs. Glucose turnover (Ra) was estimated using a priming dose of [3-3H]glucose and [1-14C]-glucose followed by constant intravenous infusion. Glucose recycling was calculated from 3H-Ra - 14C-Ra. In eight normal dogs, mean 3H-Ra was 3.0 mg X kg-1 X min-1 and recycling 19%. When these dogs were made diabetic with alloxan and streptozotocin the 3H-Ra rose to 6.2 mg X kg-1 X min-1 (P less than 0.001) and recycling to 24% (P less than 0.05). Insulin infusion for 2.5 h at 0.006 U X kg-1 X h-1 intraportally decreased 3H-Ra to 4.0 mg X kg-1 X min-1 (P less than 0.01 compared with untreated diabetic), whereas peripheral infusion at this rate had no significant effect. Insulin infusion at 0.05 U X kg-1 X h-1 by the peripheral and portal circulations reduced 3H-Ra to the normal range: 3.1 and 2.8 mg X kg-1 X min-1, respectively. Glucose recycling was also normalized by portal insulin infusion (20%) but was significantly decreased by peripheral infusion (11%, P less than 0.01). Thus the liver responds to lower infusion rates of insulin by the intraportal route, and only this mode of administration normalizes both hepatic glucose output and glucose recycling.