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Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0002-4245-7565
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
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2016 (English)In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 23, no 7, 597-605 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load.

METHODS: Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI).

RESULTS: Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load.

CONCLUSION: Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016. Vol. 23, no 7, 597-605 p.
National Category
Endocrinology and Diabetes Physiology Clinical Medicine Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:liu:diva-132368DOI: 10.1111/micc.12325ISI: 000386946300014PubMedID: 27681957OAI: oai:DiVA.org:liu-132368DiVA: diva2:1044067
Note

Funding agencies: ALF grants; Region Ostergotland; Sinnescentrum; Gronberg Foundation

Available from: 2016-11-01 Created: 2016-11-01 Last updated: 2016-12-06Bibliographically approved
In thesis
1. Assessment of microvascular and metabolic responses in the skin
Open this publication in new window or tab >>Assessment of microvascular and metabolic responses in the skin
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The general aim of this project was to develop experimental in vivo models that allow for minimally invasive investigations of responses in the skin to microvascular and metabolic provocations. The cutaneous microvasculature has emerged as a valuable model and been proposed to mirror the microcirculation in other organs. Dysfunction in the cutaneous microcirculation has thus been linked to systemic diseases such as hypertension and diabetes mellitus. Models for investigating skin responses could facilitate the understanding of pathophysiological mechanisms as well as effects of drugs.

In the first study, three optical measurement techniques (laser Doppler flowmetry (LDF), laser speckle contrast imaging (LSCI) and tissue viability imaging (TiVi)) were compared against each other and showed differences in their ability to detect microvascular responses to provocations in the skin. TiVi was found more sensitive for measurement of noradrenaline-induced vasoconstriction, while LSCI was more sensitive for measurement of vascular occlusion. In the second study, microvascular responses in the skin to iontophoresis of vasoactive drugs were found to depend on the drug delivery protocol. Perfusion half-life was defined and used to describe the decay in the microvascular response to a drug after iontophoresis. In the third study, the role of nitric oxide (NO) was assessed during iontophoresis of insulin. The results showed a NO-dependent vasodilation in the skin by insulin. In the fourth study the vasoactive and metabolic effects of insulin were studied after both local and endogenous administration. Local delivery of insulin increased skin blood flow, paralleled by increased skin concentrations of interstitial pyruvate and lactate, although no change in glucose concentration was observed. An oral glucose load resulted in an increased insulin concentration in the skin paralleled by an increase in blood flow, as measured using the microdialysis urea clearance technique, although no changes in perfusion was measured by LSCI.

The thesis concludes that when studying skin microvascular responses, the choice of measurement technique and the drug delivery protocol has an impact on the measurement results, and should therefore be carefully considered. The thesis also concludes that insulin has metabolic and vasodilatory effects in the skin both when administered locally and as an endogenous response to an oral glucose load. The vasodilatory effect of insulin in the skin is mediated by nitric oxide.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 51 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1534
National Category
Pharmaceutical Sciences Clinical Medicine Medical Laboratory and Measurements Technologies Bioengineering Equipment Medical Biotechnology Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:liu:diva-132167 (URN)10.3384/diss.diva-132167 (DOI)9789176857021 (Print) (ISBN)
Public defence
2016-11-18, Hugo Theorellsalen, Campus US, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2016-10-19 Created: 2016-10-19 Last updated: 2016-11-01Bibliographically approved

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The full text will be freely available from 2017-09-28 14:40
Available from 2017-09-28 14:40

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Iredahl, FredrikHögstedt, AlexandraHenricson, JoakimSjöberg, FolkeTesselaar, ErikFarnebo, Simon
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