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Postprandial interstitial insulin concentrations in type 2 diabetes relatives
Author(s) -
Sandqvist M.,
Johanson E. H.,
Ahrén B.,
Axelsen M.,
Schmelz M.,
Smith U.,
Jansson P.A.
Publication year - 2006
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2006.01647.x
Subject(s) - nateglinide , insulin , medicine , endocrinology , postprandial , adipose tissue , type 2 diabetes , microdialysis , insulin resistance , diabetes mellitus , area under the curve , placebo , white adipose tissue , alternative medicine , pathology , central nervous system
Background An endothelial barrier for the insulin transport from the circulation to the target tissues of insulin has previously been suggested to contribute to insulin resistance. The interstitial insulin concentration (I‐insulin) and insulin kinetics following a mixed meal have, however, previously not been characterized in human adipose tissue. Subjects and methods Eight nondiabetic first‐degree relatives (FDR) of type 2 diabetes patients were recruited. Their I‐insulin was measured by microdialysis after a test meal with or without oral administration of the insulin secretagogue nateglinide (120 mg). In parallel, adipose tissue blood flow and lipolysis were measured by xenon‐clearance and microdialysis, respectively. Results The I‐insulin increased after the test meal, and this response was more prominent on the day the subjects received the nateglinide tablet when compared with the day the subjects received the placebo tablet [I‐insulin incremental area under the curve (IAUC) nateglinide 7612 ± 3032 vs. Plac 4682 ± 2613 pmol L −1 min; P < 0·05, mean ± SE]. However, the postprandial I‐insulin max /P‐insulin max ratio was similar on the two test days (nateglinide: 213 ± 62 vs. 501 ± 92 pmol L −1 , I/P‐ratio: 0·38 ± 0·06 and placebo: 159 ± 39 vs. 410 ± 74 pmol L −1 , I/P‐ratio: 0·36 ± 0·05). There was no difference in time of onset of insulin action in situ , or responsiveness, when comparing placebo and nateglinide. Conclusions Microdialysis can now be used to measure the I‐insulin in human adipose tissue following a mixed meal. The data also showed that the transendothelial delivery of insulin occurs rapidly, supporting the concept that transcapillary insulin transfer is a nonsaturable process in nondiabetic first‐degree relatives of type 2 diabetes patients.