Differences in glucose control, insulin sensitivity, and body composition between metabolically healthy and unhealthy people with obesity

Poster presented at the 2017 Health Sciences Research Day which was organized and sponsored by the University of Missouri School of Medicine Research Council and held on November 9, 2017.Obesity is a significant risk factor for cardiometabolic complications, including type 2 diabetes and cardiovascular disease. However, approximately 25% of individuals with obesity are seemingly protected from these complications (Wildman et al. Arch Intern Med, 168, 1617-24, 2008). The purpose of this study was to provide a careful characterization of body composition and metabolic function in people who are: (i) lean and metabolically normal (MNL); (ii) obese and metabolically-normal (MN)); and (iii) obese and metabolically-abnormal (MAO). (Introduction & study aims) Although the glycemic responses of MNL individuals demonstrate a "metabolically healthy" state, more rigorous measures of insulin sensitivity show insulin resistance in this population, demonstrating people with MNO are insulin-resistant with respect to glucose metabolism but are able to maintain normal glycemic control by increased insulin secretion. Adipose tissue distribution is a marker of metabolic health in people with obesity, as greater intra-abdominal adipose tissue volume and intrahepatic triglyceride content are associated with metabolic dysfunction

Upregulation of Defensins in Burn Sheep Small Intestine

Objective: The aim of this study was to visualize and localize the sheep antimicrobials, β-defensins 1, 2, and 3, (SBD-1, SBD-2, SBD-3), sheep neutrophil defensin alpha (SNP-1), and the cathelicidin LL-37 in sheep small intestine after burn injury, our hypothesis being that these compounds would be upregulated in an effort to overcome a compromised endothelial lining. Response to burn injury includes the release of proinflammatory cytokines and systemic immune suppression that, if untreated, can progress to multiple organ failure and death, so protective mechanisms have to be initiated and implemented. Methods: Tissue sections were probed with antibodies to the antimicrobials and then visualized with fluorescently labeled secondary antibodies and subjected to fluorescence deconvolution microscopy and image reconstruction. Results: In both the sham and burn samples, all the aforementioned antimicrobials were seen in each of the layers of small intestine, the highest concentration being localized to the epithelium. SBD-2, SBD-3, and SNP-1 were upregulated in both enterocytes and Paneth cells, while SNP-1 and LL-37 showed increases in both the inner circular and outer longitudinal muscle layers of the muscularis externa following burn injury. Each of the defensins, except SBD-1, was also seen in between the muscle layers of the externa and while burn caused slight increases of SBD-2, SBD-3, and SNP-1 in this location, LL-37 content was significantly decreased. Conclusion: That while each of these human antimicrobials is present in multiple layers of sheep small intestine, SBD-2, SBD-3, SNP-1, and LL-37 are upregulated in the specific layers of the small intestine

Influence of adiposity, insulin resistance, and intrahepatic triglyceride content on insulin kinetics

BACKGROUNDInsulin is a key regulator of metabolic function. The effects of excess adiposity, insulin resistance, and hepatic steatosis on the complex integration of insulin secretion and hepatic and extrahepatic tissue extraction are not clear.METHODSA hyperinsulinemic-euglycemic clamp and a 3-hour oral glucose tolerance test were performed to evaluate insulin sensitivity and insulin kinetics after glucose ingestion in 3 groups: (a) lean subjects with normal intrahepatic triglyceride (IHTG) and glucose tolerance (lean-NL; n = 14), (b) obese subjects with normal IHTG and glucose tolerance (obese-NL; n = 24), and (c) obese subjects with nonalcoholic fatty liver disease (NAFLD) and prediabetes (obese-NAFLD; n = 22).RESULTSInsulin sensitivity progressively decreased and insulin secretion progressively increased from the lean-NL to the obese-NL to the obese-NAFLD groups. Fractional hepatic insulin extraction progressively decreased from the lean-NL to the obese-NL to the obese-NAFLD groups, whereas total hepatic insulin extraction (molar amount removed) was greater in the obese-NL and obese-NAFLD subjects than in the lean-NL subjects. Insulin appearance in the systemic circulation and extrahepatic insulin extraction progressively increased from the lean-NL to the obese-NL to the obese-NAFLD groups. Total hepatic insulin extraction plateaued at high rates of insulin delivery, whereas the relationship between systemic insulin appearance and total extrahepatic extraction was linear.CONCLUSIONHyperinsulinemia after glucose ingestion in obese-NL and obese-NAFLD is due to an increase in insulin secretion, without a decrease in total hepatic or extrahepatic insulin extraction. However, the liver\u27s maximum capacity to remove insulin is limited because of a saturable extraction process. The increase in insulin delivery to the liver and extrahepatic tissues in obese-NAFLD is unable to compensate for the increase in insulin resistance, resulting in impaired glucose homeostasis.TRIAL REGISTRATIONClinicalTrials.gov NCT02706262.FUNDINGNIH grants DK56341 (Nutrition Obesity Research Center), DK052574 (Digestive Disease Research Center), RR024992 (Clinical and Translational Science Award), and T32 DK007120 (a T32 Ruth L. Kirschstein National Research Service Award); the American Diabetes Foundation (1-18-ICTS-119); Janssen Research & Development; and the Pershing Square Foundation

Magnetic Field Dependence of the Level Spacing of a Small Electron Droplet

The temperature dependence of conductance resonances is used to measure the evolution with the magnetic field of the average level spacing $\Delta\epsilon$ of a droplet containing $\sim 30$ electrons created by lateral confinement of a two-dimensional electron gas in GaAs. $\Delta\epsilon$ becomes very small ($< 30\mu$eV) near two critical magnetic fields at which the symmetry of the droplet changes and these decreases of $\Delta\epsilon$ are predicted by Hartree-Fock (HF) for charge excitations. Between the two critical fields, however, the largest measured $\Delta\epsilon= 100\mu$eV is an order of magnitude smaller than predicted by HF but comparable to the Zeeman splitting at this field, which suggests that the spin degrees of freedom are important. PACS: 73.20.Dx, 73.20.MfComment: 11 pages of text in RevTeX, 4 figures in Postscript (files in the form of uuencoded compressed tar file

Characterization of antifungal C-type lectin receptor expression on murine epithelial and endothelial cells in mucosal tissues

Funding Information: We thank P. Asamaphan, A. Clark, and B. Kerscher for providing NIH overexpression cell lines, S. Yamasaki for the anti‐Mincle antibody, the staff of the University of Aberdeen animal facility for the care for our animals, and the Iain Fraser Cytometry Centre at the University of Aberdeen for their assistance. This work was supported by funding from the Wellcome Trust (102705, 217163), the Medical Research Council Centre for Medical Mycology, and the University of Exeter (MR/N006364/2).Peer reviewedPublisher PD

Tunable Kondo effect in a single donor atom

The Kondo effect has been observed in a single gate-tunable atom. The measurement device consists of a single As dopant incorporated in a Silicon nanostructure. The atomic orbitals of the dopant are tunable by the gate electric field. When they are tuned such that the ground state of the atomic system becomes a (nearly) degenerate superposition of two of the Silicon valleys, an exotic and hitherto unobserved valley Kondo effect appears. Together with the regular spin Kondo, the tunable valley Kondo effect allows for reversible electrical control over the symmetry of the Kondo ground state from an SU(2)- to an SU(4) -configuration.Comment: 10 pages, 8 figure