To investigate the short-term effects of didecanoyl-L-α-phosphatidylcholine on the nasal mucosa and the mechanism by which didecanoyl-L-α-phosphatidylcholine enhances the nasal absorption of insulin, an in vitro model was developed. The mucosa from the posterior part of the rabbit nasal septum was mounted in an Ussing chamber and incubated in bicarbonate Ringer solution at 37°C. Potential difference, transmucosal conductance, and unidirectional tracer fluxes were measured across an exposed tissue area of 0.44 cm2. Morphological and physiological examinations revealed a typical respiratory epithelium containing amiloride-sensitive Na+ channels and diphenylamine-2-carboxylate–sensitive Cl− channels. Spontaneous potential difference (10.8 ± 0.4 mV [n = 50]; serosa positive) and transmucosal conductance (10.5 ± 0.4 mS/cm2 [n = 50]) were stable for several hours. Mucosal addition of 0.1–0.5% didecanoyl-L-α-phosphatidylcholine increased transmucosal conductance (by 43–53%) and decreased potential difference (to 0–2 mV) to new steady-state values within 10–15 min. Control unidirectional rate constants for permeation of sucrose, polyethylene glycol 4000, and insulin were low and varied according to the molecular size. After addition of didecanoyl-L-α-phosphatidylcholine, unidirectional rate constants for the three compounds all increased 3- to 5.5-fold. The didecanoyl-L-α-phosphatidylcholine effects on potential difference and transmucosal conductance were reversible after a recovery period of at least 40 min when didecanoyl-L-α-phosphatidylcholine had been applied to the mucosal side for 15 min. The results suggest that didecanoyl-L-α-phosphatidylcholine may increase the transepithelial absorption of insulin by facilitating a paracellular passage through a reversible opening of tight junctions.
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Original Articles|
July 01 1993
Transport of Insulin Across Rabbit Nasal Mucosa In Vitro Induced by Didecanoyl-L-α-Phosphatidylcholine
Søren Carstens;
Søren Carstens
University Institute of Experimental Medicine
Copenhagen, Denmark
Diabetes Research and CNS Division, Novo Nordisk A/S Bagsvaerd
Denmark
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Gillian Danielsen;
Gillian Danielsen
University Institute of Experimental Medicine
Copenhagen, Denmark
Diabetes Research and CNS Division, Novo Nordisk A/S Bagsvaerd
Denmark
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Birgitte Guldhammer;
Birgitte Guldhammer
University Institute of Experimental Medicine
Copenhagen, Denmark
Diabetes Research and CNS Division, Novo Nordisk A/S Bagsvaerd
Denmark
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Ole Frederiksen
Ole Frederiksen
University Institute of Experimental Medicine
Copenhagen, Denmark
Diabetes Research and CNS Division, Novo Nordisk A/S Bagsvaerd
Denmark
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Address correspondence and reprint requests to Dr. Ole Frederiksen, University Institute of Experimental Medicine, The Panum Institute, Building 10.5, 3 Blegdamsvej, DK-2200 Copenhagen N, Denmark.
Diabetes 1993;42(7):1032–1040
Article history
Received:
April 11 1992
Revision Received:
February 09 1993
Accepted:
February 09 1993
PubMed:
8513970
Citation
Søren Carstens, Gillian Danielsen, Birgitte Guldhammer, Ole Frederiksen; Transport of Insulin Across Rabbit Nasal Mucosa In Vitro Induced by Didecanoyl-L-α-Phosphatidylcholine. Diabetes 1 July 1993; 42 (7): 1032–1040. https://doi.org/10.2337/diab.42.7.1032
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