Effects of subbasal insulin infusion on resting and exercise-induced glucose turnover in depancreatized dogs

Abstract

beta-Adrenergic blockade suppressed lipolysis and normalized the exercise-induced increments in glucose uptake (GlcU) and metabolic clearance rate (MCR) in alloxan-diabetic dogs with residual insulin, but not in insulin-deprived depancreatized dogs even when combined with methylpalmoxirate (MP), which suppresses fatty acid oxidation. The effects of a minimal amount of insulin (as in the alloxan-diabetic dog), were studied in depancreatized, 24-h insulin-deprived dogs during rest and treadmill exercise (6 km/h, 10% slope) using a 1/4 basal insulin infusion (50 microU.kg-1.min-1, insulin, n = 6) alone, or with MP (20 mg.kg-1.day orally, 2.5 days, MP+insulin, n = 6). At rest, insulin decreased circulating fatty acids (31%) and Glc (13%) and increased GlcU and MCR (86 and 72%). Glc production was unaffected. MP plus insulin markedly suppressed hepatic fatty acid oxidation, decreased Glc (44%) and Glc production (50%), and markedly increased MCR (128%). The exercise-induced increments in MCR were markedly improved only by MP plus insulin but were still lower than in the propranolol-treated alloxan-diabetic dogs. Plasma Glc inversely correlated with the exercise-induced increase in MCR (r = -0.86). We conclude that 1) acute infusion of subbasal insulin improved GlcU in depancreatized dogs at rest but not during exercise; 2) inhibition of fatty acid oxidation combined with subbasal insulin improved the exercise-induced increase in MCR; and 3) the difference in GlcU and MCR between the MP plus insulin-treated depancreatized dogs and the beta-blockade-treated alloxan-diabetic dogs suggests a difference between acute and chronic effects of insulin.