Browsing by Author "Jochim, Alexander"

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    G Protein-Coupled Receptor 17 Inhibits Glucagon-like Peptide-1 Secretion via a Gi/o-Dependent Mechanism in Enteroendocrine Cells
    (MDPI, 2024-12-25) Conley, Jason M.; Jochim, Alexander; Evans-Molina, Carmella; Watts, Val J.; Ren, Hongxia; Pediatrics, School of Medicine
    Gut peptides, including glucagon-like peptide-1 (GLP-1), regulate metabolic homeostasis and have emerged as the basis for multiple state-of-the-art diabetes and obesity therapies. We previously showed that G protein-coupled receptor 17 (GPR17) is expressed in intestinal enteroendocrine cells (EECs) and modulates nutrient-induced GLP-1 secretion. However, the GPR17-mediated molecular signaling pathways in EECs have yet to be fully deciphered. Here, we expressed the human GPR17 long isoform (hGPR17L) in GLUTag cells, a murine EEC line, and we used the GPR17 synthetic agonist MDL29,951 together with pharmacological probes and genetic approaches to quantitatively assess the contribution of GPR17 signaling to GLP-1 secretion. Constitutive hGPR17L activity inhibited GLP-1 secretion, and MDL29,951 treatment further inhibited this secretion, which was attenuated by treatment with the GPR17 antagonist HAMI3379. MDL29,951 promoted both Gi/o and Gq protein coupling to mediate cyclic AMP (cAMP) and calcium signaling. hGPR17L regulation of GLP-1 secretion appeared to be Gq-independent and dependent upon Gi/o signaling, but was not correlated with MDL29,951-induced whole-cell cAMP signaling. Our studies revealed key signaling mechanisms underlying the role of GPR17 in regulating GLP-1 secretion and suggest future opportunities for pharmacologically targeting GPR17 with inverse agonists to maximize GLP-1 secretion.
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    Understanding the Role of Cues in Predicting Physical Activity Behavior
    (2023-06) Jochim, Alexander; Kaushal, Navin; Munk, Niki; Wierenga, Kelly
    Cues have been theorized to promote health behaviors but currently our understanding of the effectiveness of cues is inconclusive. The purpose of this systematic review was to assess the effectiveness of cue interventions in promoting physical activity (PA). Six databases were searched which captured 3,996 articles. After comparison with the eligibility criteria, 19 articles were included in the review. Data extraction revealed that while cues were effective in increasing PA behavior, less than half of the studies (n = 8) were supported by theory-based methodologies. We concluded that cue-based interventions are effective for promoting PA behavior, but future research must develop valid measures of cues and incorporate theory into their study designs. The purpose of the thesis study aimed to address this gap by testing if cue consistency would help explain PA habit and behavior through the Dual Process approach. We conducted an observational study with two measurement periods. We recruited 196 participants via an online volunteer registry. Participants completed measures of exercise behavior, intention, habit, perceived behavioral control (PBC), affective attitudes, and cue consistency at baseline and one month later. We ran a Hierarchical Multiple Regression analysis to determine whether a) habit, intention, PBC, affective attitudes, and cue consistency predicted moderate-vigorous physical activity (MVPA) and b) whether PBC, affective attitudes, and cue consistency predicted habit. Our results showed that MVPA was significantly predicted by habit (β = 0.23, p < 0.01), intention (β = 0.16, p < 0.05), PBC (β = 0.23, p < 0.01), affective attitudes (β = 0.20, p < 0.05), and cue consistency (β = -0.20, p < 0.05). Habit was predicted by affective attitudes (β = 0.48, p < 0.001) and cue consistency (β = 0.32, p < 0.001), but PBC (β = 0.10, p = 0.11) was not significant. We found a stronger relationship between cue consistency and habit than previous studies that evaluated cues individually, supporting the cue consistency construct. Our results suggest that cue consistency should be incorporated in the Dual Process approach as a determinant of habit. Future research should look to replicate our findings through cue-based interventions grounded in theory.