Intrapulmonary insulin : Experimental and clinical studies

Sammanfattning: After intrapulmonary insulin administration was first reported in 1925, the development of highly efficient nebulisers has once again made this area interesting. Therefore, the distribution and retention of aerosol produced by a new jet nebuliser was evaluated in an animal model. Anaesthetized and mechanically ventilated pigs were given radiolabelled aerosol, insulin or the combination of insulin and a surface active agent. After sacrifice the lungs were histologically examined or scintigrafted using a gamma camera. The distribution of aerosol was even and reached the peripheral parts of the lung parenchyma. The retention of insulin was estimated to be 36%. No morfological changes were observed.The biological effects of intrapulmonary insulin administration were evaluated in 14 pigs in a double-blind placebo controlled randomized intervention trial. Insulin at a dose of 10 and 40 U as well as 0.9% saline solution was given as aerosol. The blood glucose and serum insulin concentrations were assessed at certain intervals during 90 min. The mean blood glucose concentration fell from 4.6 ± 0.1 to 2.8 ± 0.2 mmol/L reaching a nadir 40 min after the start of nebulisation. Serum insulin rose from 5.2 ± 0.1 to 25 ± 9 mUlL.Eight healthy volunteers received insulin aerosol in three different doses (40, 80 and 160 U) in a double-blind randomized intervention study. As a control saline solution was given. Blood glucose, serum insulin and serum C-peptide were assessed during 120 min. A reduction of the mean bloodglucose concentration was seen, falling from 4.3 ± 0.2 to 2.8 ± 0.2 mmol/L after 160 U. Serum insulin rose from 9.5 ± 1.5 mUlL to 26.1 ± 2.5 mUlL. Serum C-peptide was suppressed in a dosedependent fashion.Twelve patients with NIDDM treated with anti-diabetic drugs were given intrapulmonary insulin in a double-blind randomized intervention trial. Insulin was given at a dose of 2.5 U/kg BW. As a control saline solution was given. Blood glucose, serum insulin and serum C-peptide were assessed during 180 min. Blood glucose fell from 10.2 ± 0.5 to 6.1 ± 0.5 mmol/L. Serum insulin rose from 11.2 ± 1.8 to 28.0 ± 2.6 mUlL. Likewise serum C-peptide was suppressed after inhaling the insulin aerosol.A flow cytometric assay was developed to assess the changes of the F-actin content and DNA synthesis in adherent cells after short-time and long-term stimulation with insulin and PDGF. No stimulatory effect on the DNA synthesis was seen on lung fibroblasts after repetitive insulin treatment.Thus, intrapulmonary insulin administration has been evaluated in experimental and clinical studies. Significant lowering of the blood glucose concentrations and clinically relevant serum insulin concentrations were achieved. No subjective adverse effects were reported. No changes in lung function could be observed experimentally.