Skin: A Proxy Tissue for the Investigation of Whole Body Glucose Homeostasis

Presentation Number: SUN 576
Date of Presentation: April 2nd, 2017

Dylan T Ryan*1, Logan B DeHoff1, Leryn J Reynolds1, Sara Y Ngo Tenlep1, Josh D Preston1 and Kevin J. Pearson2
1University of Kentucky College of Medicine, 2University of Kentucky College of Medicine, Lexington, KY

Abstract

Abstract: Maternal nutrition and behaviors during pregnancy contribute significantly to offspring risk of obesity, type II diabetes mellitus, and cardiovascular disease later in life. Previous studies examined maternal exposures utilizing the placenta and cord blood, but our laboratory has begun to investigate the mechanisms of in utero metabolic programming in infants using neonatal skin. Human skin makes up approximately 15% of body weight and it has been shown that human fibroblasts express glucose transporters. Our lab showed that fibroblasts isolated from the dermal layer of the foreskin significantly increase AKT phosphorylation in response to insulin stimulation. These data led us to hypothesize that skin can be used as a surrogate tissue to study whole body glucose metabolism. Thus, we performed an experiment where mice (n = 10) were injected with 3H radiolabeled 2-deoxyglucose (2-DG) and unlabeled glucose as part of a glucose tolerance test. Tissue glucose uptake was quantified in numerous organs including the skin, adipose, and skeletal muscle. Importantly, skin glucose uptake per mg tissue weight was significantly positively correlated to glucose uptake per mg tissue weight in both visceral fat (R = 0.961, P < 0.01) and the extensor digitorum longus muscle (R = 0.692, P < 0.05), two tissues that are thought to be metabolically active and insulin responsive. Most importantly, the skin was negatively correlated with the area under the curve (AUC) of the glucose disposal after 45 minutes (R = -0.837, P < 0.01). These data can be interpreted to mean that high levels of glucose uptake in the skin are indicative of better glucose disposal. From our results, we speculate that the skin is a useful proxy tissue to investigate whole body glucose homeostasis and the neonatal foreskin should be a relevant tissue of interest to study the developmental programming of insulin resistance.

 

Nothing to Disclose: DTR, LBD, LJR, SYN, JDP, KJP