| 1. |
- Jendle, Johan, 1963-, et al.
(författare)
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An exploration of intrapulmonary insulin administration in anaesthetized and mechanically ventilated pigs
- 1996
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 56:3, s. 251-258
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the efficacy of intrapulmonary administration of short-acting porcine insulin in anaesthetized pigs (n = 14) in a randomized intervention study. Insulin was administered by a new jet nebulizer (Maxin) in a random order at different doses, 0 (saline), 10 or 40 U. The hypoglycaemic effect was compared to control (0.9% saline). Blood glucose and serum insulin concentrations were followed at specified time intervals for 90 min. Plasma catecholamine concentrations were measured in order to estimate the concurrent stress. Nebulized insulin caused a significant decrease in blood glucose concentrations (p < 0.0001) (n = 28) at all doses used. The decrease in mean blood glucose concentration from the start of nebulization was 39 +/- 3% (mean +/- SEM), falling from 4.6 +/- 0.1 to 2.8 +/- 0.2 mmol 1(-1), with a nadir at 40 min after the 40 U insulin dose (n = 10). Serum insulin concentration rose from (mean +/- SEM) 5.2 +/- 0.1 to 25 +/- 9 mU 1(-1) after the insulin dose of 40 U (n = 10), the peak value occurred at 30 min. The plasma catecholamine concentrations increased significantly (p < 0.0001) (n = 28) from 0 to 60 min, this increase was similar for control and for different insulin doses. We conclude that intrapulmonary administration of insulin can cause a significant decrease in blood glucose concentrations in anaesthetized and mechanically ventilated pigs and results in clinically relevant serum insulin levels. Similar effects in humans would make inhaled insulin possible for clinical use.
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| 2. |
- Jendle, Johan, 1963-, et al.
(författare)
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Delivery and Retention of an Insulin Aerosol Produced by a New Jet Nebulizer
- 1995
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Ingår i: Journal of Aerosol Medicine. - : Mary Ann Liebert. - 0894-2684 .- 1557-9026. ; 8:3, s. 243-254
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: This study describes the delivery and distribution of an aerosol generated by a jet nebulizer (MAXIN) in an experimental animal model. Anesthetised, intubated and ventilated piglets inhaled radiolabeled technetium diethylene-triamine-penta-acetic acid (99mTc-DTPA) through the endotracheal tube. The lungs were excised en bloc and scintigraphed, using a computerized gamma camera to evaluate the pattern of distribution. By nebulizing radiolabeled 125I-insulin and comparing the activity deposited on inspiratory and expiratory electrostatic filters, delivery and retention of nebulized insulin was assessed. The distribution of aerosol in the lungs was very even and reached the most peripheral parts. The delivery of nebulized insulin was calculated to be 88.9 +/- 5.3% and 36.1 +/- 8.8% of the insulin delivered to the respiratory tract was retained. The immediate local effects of insulin aerosol administration on the lungs were evaluated using light microscopy. No adverse effects were observed at histopathologic examination of the lung tissue.CONCLUSION: This study shows a high penetration of aerosol to the peripheral parts of the lung and efficient delivery of nebulized insulin when using the MAXIN-nebulizer.
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| 3. |
- Jendle, Johan, 1963-, et al.
(författare)
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Effects of intrapulmonary insulin in patients with non-insulin-dependent diabetes
- 1996
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 56:6, s. 555-561
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Tidskriftsartikel (refereegranskat)abstract
- The effects of intrapulmonary insulin administration in non-insulin-dependent diabetes mellitus (NIDDM) were studied in 12 patients in a double-blind randomized placebo-controlled intervention study. Regular human insulin, 100 U ml-1, was given as an aerosol by oral inhalation after a 12-h fasting. A significant decrease in blood glucose concentration, from 10.2 +/- 0.5 to 6.1 +/- 0.5 mmol l-1 (p < 0.0001) and a significant rise in serum insulin concentration, from 11.2 +/- 1.8 to 28.0 +/- 2.6 mU ml-1 (p < 0.0001), was seen. Serum C-peptide levels decreased from 1.6 +/- 0.2 to 1.0 +/- 0.1 nmol l-1 (p < 0.0001). No side-effects were reported following aerosol inhalation. If similar results can be obtained when using this route for insulin administration to insulin-dependent diabetes mellitus patients, this may be a useful complement to traditional subcutaneous insulin injections in these patients.
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| 4. |
- Jendle, Johan, 1963-, et al.
(författare)
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Intrapulmonary administration of insulin to healthy volunteers
- 1996
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Ingår i: Journal of Internal Medicine. - : Blackwell Science Ltd.. - 0954-6820 .- 1365-2796. ; 240:2, s. 93-98
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the biological effects of nebulized insulin, administered intrapulmonary, to healthy volunteers.DESIGN: A double-blind, randomized, controlled intervention study.SETTING: The department of Internal Medicine, University Hospital, Linköping, Sweden.SUBJECTS: Eight healthy, non-smoking volunteers, with a mean age of 28 (range 22 to 56) years.INTERVENTIONS: Regular human insulin 100 U mL-1 (Actrapid) or 0.9% saline was given randomly as an oral inhalation. Insulin was given in three different doses (40, 80 and 160 U). Aerosol was generated by a new jet nebulizer.MAIN OUTCOME MEASURES: Blood glucose, serum insulin, and serum C-peptide.RESULTS: After the 160 U insulin dose the blood glucose concentration (mean +/- SE) fell from 4.3 +/- 0.2 to 2.8 +/- 0.2 mmol L-1 (P < 0.001), concomitant with an increase in mean serum insulin concentrations, rising from 9.5 +/- 1.5 to 26.1 +/- 2.5 mU L-1 (P < 0.001). Serum C-peptide concentrations simultaneously decreased from 0.48 +/- 0.03 to 0.12 +/- 0.02 mmol L-1 (P < 0.001). All changes were dose dependent. No adverse reactions were noted and no significant changes in lung function tests.CONCLUSIONS: Intrapulmonary insulin administration to healthy subjects can induce a significant hypoglycaemia and cause a clinically relevant increase in serum insulin concentrations. If similar results can be obtained when administering insulin to diabetic subjects, this insulin administration route can be a future complement to certain groups of patients.
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