Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load

Abstract

Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load, Microcirculation, 2016. 23 (7) Grants:The study has been financially supported by ALF grants, Region Östergötland, by Sinnescentrum, Region Östergötland, and by The Grönberg Foundation. Keywords:Insulin, Skin, Metabolism, Microcirculation, Microdialysis AbstractInsulin 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 using intracutaneous microdialysis and laser speckle contrast imaging (LSCI).Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: p=0.047, LSCI: p=0.002) paralleled by increases in pyruvate (p=0.01) and lactate (p=0.04), indicating an increase in glucose uptake. Thus, local delivery of insulin to the skin via microdialysis resulted in rapid vasodilatation, paralleled by an increased 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 time course of the effects of insulin on glucose uptake in the skin differed markedly depending on whether insulin is delivered directly to the interstitium via microdialysis, or via a systemic route. These results show that insulin has specific metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load.

Lamellar energy metabolism and perfusion in the euglycaemic hyperinsulinaemic clamp model of equine laminitis

“…Although increased hoof wall surface temperature in a previous EHC study was attributed to increased perfusion, this parameter may be affected by confounding factors including perfusion though arteriovenous anastomoses (bypassing the nutrient capillary bed) and changes in tissue metabolic rate, therefore this study provides the first evidence of increased lamellar microvascular perfusion during laminitis development in the EHC. These findings are consistent with those in human skin where exposure to excess insulin caused an increase in perfusion demonstrated by increased microdialysis urea clearance . Insulin causes vasodilation in most studied tissues by binding endothelial cell IR, activating PI3K signalling and causing nitric oxide (NO) production and release .…”

“…As the lamellar epithelium lacks insulin receptors (IR) and previous studies have demonstrated that lamellar glucose uptake is non‐insulin dependent, a direct (IR‐mediated) effect of hyperinsulinaemia on glucose uptake was not expected. However, in this study lactate and pyruvate concentrations increased in EHC horses suggesting an increased rate of glucose metabolism, an effect that was also observed in a microdialysis study of human skin exposed to insulin . Although lamellar epithelial cells lack IR, they are rich in IGF‐1R and there is evidence that signalling pathways downstream from IGF‐1R are activated during the EHC, including the phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway which directly and indirectly increases cellular metabolic rate and nutrient demands .…”

Response of Blood Perfusion at ST 36 Acupoint after Drinking Cold Glucose or Saline Injection

“…Previous study indicated that insulin has vasoactive properties [32]. Furthermore, other evidence indicated that insulin causes vasodilatation in the microcirculation in the skin both when given locally and after systemic delivery through an oral glucose load [33]. In this study, the blood perfusion of right ST 36 in G-group is higher than S-group, which might result from insulin action after oral glucose load.…”

Studies on the pathogenesis of insulin-induced laminitis in horses

“…In a recent study of horses undergoing the EHC model, there was evidence of increased lamellar perfusion during the development of laminitis, indicated by an increased in hoof wall surface temperature [22]. Furthermore, a similar finding has been observed in a microdialysis study of human skin exposed to insulin, which observed an increase in microvascular skin perfusion [133]. However, while there is some evidence that lamellar vasodilation occurs in the EHC model, a recent study found that the infusion of a potent vasodilator (ATP-MgCl2) over a 48 hour period in healthy Standardbred horses does not induce laminitis [134].…”