Inhaled Insulin Shows Prolonged Effect on Glucose Disposal in Canines

Scientists at Vanderbilt University have discovered that diabetic patients treated with inhaled insulin exhibit reduced fasting plasma glucose levels, a finding that was confirmed in a study involving dogs. The researchers administered human insulin via inhalation or infusion to dogs, observing that glucose utilization was greater when insulin was administered by inhalation. The study, published in the Journal of Pharmacology and Experimental Therapeutics, suggests that this effect may explain the reduced fasting glucose concentrations observed in humans after administration of certain inhaled insulin formulations compared with subcutaneous insulin.

Key Takeaways:

• Inhaled insulin was associated with greater glucose disposal in dogs, with a 50% difference between groups persisting over 8 hours.
• The peripheral glucose infusion rate was 4 mg/kg/min greater in the inhalation group, and this difference persisted for 3 hours after inhalation.
• Net hepatic glucose uptake was greater in the inhalation group, and inhalation of insulin caused a greater increase in nonhepatic glucose uptake in the first 3 hours after inhalation.
• The researchers concluded that this effect may explain the reduced fasting glucose concentrations observed in humans after administration of certain inhaled insulin formulations compared with subcutaneous insulin.
• The study involved 9 dogs in each group, administered either human insulin via inhalation or infusion.
• The researchers used an infusion algorithm to yield matched plasma insulin kinetics between the two groups.

Statistics:

• 50% difference in glucose disposal between groups persisted over 8 hours.
• Peripheral glucose infusion rate was 4 mg/kg/min greater in the inhalation group.
• 9 dogs were used in each group, administered either human insulin via inhalation or infusion.
• The infusion algorithm yielded matched plasma insulin kinetics between the two groups.
• 160 mg/dl was the arterial plasma glucose level maintained throughout the study.
• 165 mg/dl was the portal vein glucose level administered throughout the study.
• 4 mg/kg/min was the glucose infusion rate in the peripheral vein.

Sources:

• D.S. Edgerton and colleagues, Vanderbilt University. Inhaled Insulin Is Associated with Prolonged Enhancement of Glucose Disposal in Muscle and Liver in the Canine. Journal of Pharmacology and Experimental Therapeutics, 2009;328(3):970-975.
• American Society Pharmacology Experimental Therapeutics. Publisher's contact information: 9650 Rockville Pike, Bethesda, MD 20814-3995, USA.
• Vanderbilt University. Contact information: D.S. Edgerton, Medical Center, 710 Robinson Research Bldg, Nashville, TN 37232, USA.