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Incretin receptor agonists have been effective in combatting obesity and diabetes. While the body of knowledge regarding the signaling mechanisms of glucagon-like peptide 1 (GLP-1) receptor agonists is ever-growing, glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists are less understood. The previewed papers offer insight into the impact of adipose GIPR on energy and weight homeostasis. [ABSTRACT FROM AUTHOR]

Cancer-related fatigue (CRF) is one of the most common complications in patients with multiple cancer types and severely affects patients' quality of life. However, there have only been single symptom-relieving adjuvant therapies but no effective pharmaceutical treatment for the CRF syndrome. Dichloroacetate (DCA), a small molecule inhibitor of pyruvate dehydrogenase kinase, has been tested as a potential therapy to slow tumor growth, based largely on its effects in vitro to halt cell division. We found that although DCA did not affect rates of tumor growth or the efficacy of standard cancer treatment (immunotherapy and chemotherapy) in two murine cancer models, DCA preserved physical function in mice with late-stage tumors by reducing circulating lactate concentrations. In vivo liquid chromatography-mass spectrometry/mass spectrometry studies suggest that DCA treatment may preserve membrane potential, postpone proteolysis, and relieve oxidative stress in muscles of tumor-bearing mice. In all, this study provides evidence for DCA as a novel pharmaceutical treatment to maintain physical function and motivation in murine models of CRF. [ABSTRACT FROM AUTHOR]

Context Identification of insulin resistance (IR) in South Asians, who are at a higher risk for type 2 diabetes, is important. Lack of standardization of insulin assays limits the clinical use of insulin-based surrogate indices. The lipoprotein insulin resistance index (LP-IR), a metabolomic marker, reflects the lipoprotein abnormalities observed in IR. The reliability of the LP-IR index in South Asians is unknown. Objective We evaluated the predictive accuracy of LP-IR compared with other IR surrogate indices in South Asians. Methods In a cross-sectional study (n = 55), we used calibration model analysis to assess the ability of the LP-IR score and other simple surrogate indices (Homeostatic Model Assessment of Insulin Resistance, Quantitative insulin sensitivity check index, Adipose insulin resistance index, and Matsuda Index) to predict insulin sensitivity (SI) derived from the reference frequently sampled intravenous glucose tolerance test. LP-IR index was derived from lipoprotein particle concentrations and sizes measured by nuclear magnetic resonance spectroscopy. Predictive accuracy was determined by root mean squared error (RMSE) of prediction and leave-one-out cross-validation type RMSE of prediction (CVPE). The optimal cut-off of the LP-IR index was determined by the area under the receiver operating characteristic curve (AUROC) and the Youden index. Results The simple surrogate indices showed moderate correlations with SI (r = 0.53-0.69, P <.0001). CVPE and RMSE were not different in any of the surrogate indices when compared with LP-IR. The AUROC was 0.77 (95% CI 0.64-0.89). The optimal cut-off for IR in South Asians was LP-IR >48 (sensitivity: 75%, specificity: 70%). Conclusion The LP-IR index is a simple, accurate, and clinically useful test to assess IR in South Asians. [ABSTRACT FROM AUTHOR]