bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inspiratory Muscle Strength Training to Improve Cardiometabolic Health in Patients with Type 2 Diabetes Mellitus
Authors: Reed Baylee L. , Gamez Gonzalez Esmeralda , Tavoian Dallin , Bailey E. Fiona , Funk Janet L. , Coletta Dawn K. 
Published: May 2024

Type 2 diabetes mellitus (T2DM) is a complex, chronic metabolic disease that is associated with a high prevalence of comorbid conditions. Traditional lifestyle interventions (e.g., diet and exercise) can counter some adverse effects of T2DM; however, participation in these activities is low. High-resistance inspiratory muscle strength training (IMST) is a time-effcient and simple breathing exercise that significantly reduces blood pressure (BP) and improves vascular endothelial function in several nondiabetic populations. Herein, we performed a blinded, randomized, sham-controlled trial to investigate the effects of a 6-week IMST regimen (30 breaths/day, 6 days/week) on glycemic control and insulin sensitivity in adults with T2DM. Currently, we have eight participants (aged 35-71 years, 5 females and 3 males) who have completed either low-resistance sham training (15% maximal inspiratory mouth pressure, n=5) or high-resistance IMST (75% maximal inspiratory mouth pressure, n=3). Our data suggests that fasting plasma glucose and fasting serum insulin did not significantly change by IMST or sham training. Utilizing a homeostatic model assessment of insulin sensitivity to evaluate insulin action, our results indicate no change by either IMST or sham training. IMST revealed a trend towards a reduction in systolic BP (pre: 133.0 ± 4.8 vs. post: 128.8 ± 4.9) and diastolic BP (pre: 84.8 ± 2.7 vs. post: 81.7 ± 3.6). These findings align with prior research indicating improved resting BP, further corroborating previous studies. We performed an exploratory analysis to examine the potential impact of IMST on lipid levels. Interestingly, IMST resulted in a trend towards a reduction in cholesterol (pre: 259.3 ± 29.4 vs. post: 230.3 ± 3.7) and LDL (pre: 153.3 ± 19.7 vs. post: 127.7 ± 8.7). Analysis of the endothelial function data is forthcoming until we have enough individuals to complete those analyses. In conclusion, our results to date are preliminary; however, we expect to see continued improvements in resting BP and cholesterol/LDL with IMST. Moreover, with a higher number of individuals in the study (our goal is to have 12 in each group), we anticipate seeing changes in glycemia or insulin action. Lastly, IMST stands out as a distinctive and time-effective exercise method, addressing adherence challenges while demonstrating enhancements in cardiometabolic health. This could be particularly advantageous for T2DM patients with an increased cardiovascular disease risk. University of Arizona College of Medicine SPARK Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Advanced Age Impairs the Neuromuscular Control of Peak Inspiratory Performance in Mice
Authors: Murphy Ben , Maxwell Michael , Marullo Anthony , O'Halloran Ken 
Published: May 2024

Respiratory muscle wasting is known to occur in ageing adults resulting in a decreased capacity for force production and an associated reduction in high-threshold respiratory performance. Dysfunction of the respiratory musculature in this manner may contribute to an increased susceptibility to respiratory complications frequently observed in older populations. The objective of the current study was to characterise the respiratory phenotype during advanced age to assess the impact of sarcopenia on the neuromuscular control of respiratory performance. Male wild type (BL10) mice were studied at 6-months and 24-months, representing young and old age cohorts, respectively. In anaesthetised animals, inspiratory pressure and contemporaneous obligatory and accessory respiratory muscle electromyography (EMG) activities were measured during baseline and sustained tracheal occlusion (n = 9 young; n = 8 old). Diaphragm muscle contractile performance was assessed ex-vivo via tissue bath preparations (n = 8 young; n = 8 old). Furthermore, diaphragm and limb muscle tissues were harvested and snap frozen for subsequent structural and molecular analyses which will assess potential differences in cross-sectional area and relative fibre type composition. Peak inspiratory pressure was significantly reduced in 24-month-old compared to 6-month-old mice (P < 0.0001). Associated EMG activity was significantly lower (P < 0.05) in obligatory (external intercostal; parasternal) and accessory (cleidomastoid; scalene; trapezius; sternomastoid; sternohyoid) muscles of breathing in the old group compared to the young. Diaphragm EMG amplitude was not different between the groups. No differences were observed in the force-generating capacity of the diaphragm between young and old cohorts. Our preliminary results suggest an impairment in the neuromuscular control of the respiratory system during peak performance which apparently precedes the age-related decline in diaphragm muscle force generating capacity. Our further histological and molecular analyses will provide additional insight into the nature of this respiratory phenotype in advanced age. This work was funded by the Department of Physiology, UCC. B.T. Murphy is funded by an Irish Research Council Doctoral Scholarship. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Adaptations to maternal WSD-feeding and metformin use on fetal islets from non-human primate offspring
Authors: Thomas Carroll Darian , Fuhr Jennifer , Lindsley Rene , Kirigiti Melissa , Dean Tyler , McCurdy Carrie , Wesolowski Stephanie 
Published: May 2024

Given the current increased prevalence of diabetes in pregnancy, the potential relative risks and benefits of oral glycemic agents on the developing offspring should be evaluated and considered. Metformin (Met) is a common oral glycemic agent prescribed in pregnancy that is not metabolized, but is renally excreted and actively transported across the placenta. Thus, the developing fetus is exposed to near equivalent maternal adult doses with subsequent risk of adverse consequences. Using a non-human primate model of maternal overnutrition, our group previously demonstrated that developmental exposure to a Western-style diet (WSD) results in an inappropriate increase in glucose-stimulated insulin secretion and changes in expression of several ion channels involved in insulin secretion in islets from juvenile offspring. Given that maternal overnutrition results in an excess energy supply to the developing fetus while Met inhibits mitochondrial respiration, we hypothesize that maternal WSD-feeding and Met will result in maladaptive beta-cell function in the fetus. Static insulin secretion assays on islets from chow (CD) and WSD +/- Met-exposed offspring show no differences in glucose-stimulated insulin secretion. Nevertheless, islets from a mWSD+Met-exposed fetus showed lower oxygen consumption and extracellular acidification rate relative to mWSD+placebo fetal islets, suggesting that maternal diet influences fetal programming and adaptation to Met in fetal islets. Therefore, we predict that the metabolic response to intrauterine Met exposure differs depending on the maternal diet. Elucidation of the mechanisms mediating adaptations to maternal diet and Met exposure during development may provide insight on interventions to avoid beta-cell failure in the offspring as they age. All nonhuman primate studies were supported in part by the Oregon National Primate Research Center grant P51 OD011092 from the National Institutes of Health/Offce of the Director. D.T.C. was supported by the Vanderbilt University Training Program in Molecular Endocrinology (5T32 DK563-30) and a predoctoral fellowship from the NIH/NIDDK (1F31 DK135164).T.A.D., C.E.M., K.M.A., J.E.F., P.K., and M.G. were supported by NIH/NIDDK Grants R24 DK090964 and R01 DK128187. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Elevated sympathoadrenal response following active ascent to 3,600m is not associated with acute mountain sickness
Authors: Berkemeier Quint , Figueiredo Peter , Landspurg Steven , Staab Janet , Karl James , Femling Jon , Williams Jason 
Published: May 2024

Previous reports have suggested an increase in plasma epinephrine (EPI) and either an increase, no change or decrease in norepinephrine (NE) following acute (< 4 h) exposure to high altitude (HA). In addition, previous research has demonstrated an exercise-induced increase in EPI and NE during exercise initiated following arrival at HA. Last, some but not others have reported an association between increased sympathoadrenal activity and acute mountain sickness (AMS). We hypothesized that elevated sympathoadrenal activity induced from active ascent on foot to 3,600m may contribute to the development of AMS. Thirty-seven Soldiers (mean ± SD; 6 women; age=25.5±4.9 years) were tested at their baseline residence (BLR; Fort Bliss, TX, 1,190m), transported to Taos, NM (2,845m), then hiked (n=18) or were driven (n=19) to the HA data collection site where they resided for four days (68hrs). AMS Cerebral Factor Score (AMS-C) was determined using the Environmental Symptoms Questionnaire (ESQ-III) recorded twice at HA on day 1 (HA1), five times on days 2 (HA2) and 3 (HA3) and once on day 4 (HA4). If AMS-C was ≥0.7 on any measurement occasion, individuals were categorized as AMS-susceptible (AMS+, n=11) others were AMS-resistant (AMS─, n=26). Plasma EPI (pg/ml) and NE (pg/ml) were measured from venous blood draws at 06:00 at BLR, a non-fasted blood draw at 18:00 following ascent on HA1, and subsequent fasted blood samples at 06:00 on each morning at HA (HA2, HA3, HA4). AMS-susceptibility was not associated with the EPI or NE response in any condition so both cohorts were combined. The EPI response to active vs. passive ascent was similar with an increase (p<0.05) from BLR (28.0±26.8) to HA1 (47.5±40.3) followed by a subsequent decrease (p<0.05) from HA1 to HA2 (28.0±18.6) through HA4 (25.4±16.9). NE, however, increased (p<0.05) only in the active ascent group from BLR (413±216) to HA1 (729±281) and remained stable from HA1 through HA4 (644±192). The passive ascent group demonstrated no change in NE from BLR (327±126) to HA1 (413±181) through HA4 (466±144). NE levels were similar (p>0.05) in the active vs passive ascent group at BLR but higher (p<0.05) in the active ascenders on HA1 through HA4. In conclusion, contrary to our hypothesis, the sympathoadrenal response to HA was not impacted by AMS susceptibility but active ascent induced a greater NE response following ascent and throughout the duration of the HA stay. USAMRDC. Authors’ views not offcial U.S. Army or DoD policy. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Acute Exposure to High-Altitude Results in Changes to Immune Cell Populations
Authors: Vargas Abel , Mkrtchyan Karapet , Penuelas Veronica , Pham Kathy , Frost Shyleen , Moya Esteban , Yu James J 
Published: May 2024

High altitude is a challenging environment due to the reduced atmospheric pressure and oxygen availability, increased ultraviolet radiation, and reduced temperature relative to sea level. Previous studies in individuals who travel to high altitude demonstrate differential expression of genes involved in inflammation and innate immune system activation. This study aims to extend these findings by defining changes in immune cell population distributions and cell phenotypes during travel to high altitude. We hypothesized that acute high-altitude exposure would lead to shifts in immune cell populations toward a pro-inflammatory phenotype due to cellular stress caused by hypoxemia and tissue hypoxia. Participants (N=17) traveled to Barcroft Station in the White Mountain Research Center (3800 m). Whole blood was collected during fasting at sea level on the morning of ascent and each morning at high altitude for three days. Cells in whole blood were fixed and stained within 1-2 hours of collection and were processed via flow cytometry upon return to sea level. We observed a decrease in classical monocytes on the first (p=0.010) and second (p=0.003) mornings of high-altitude acclimatization to sea-level baseline, and an increase in intermediate monocytes on the first (p=0.013) and second (p=0.014) mornings at high altitude. We also observed an increase in B cells on the second (p=0.004) and third (p=0.004) mornings at high altitude compared to sea-level baseline (mean: 3.53%, SD: ±1.82). These results indicate that acute high altitude exposure results in a shift toward a pro-inflammatory monocyte phenotype and supports prior research suggesting a significant role of hypoxia in modulating B cell function. This research was supported through funding provided by a private donor. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Differences in lactate metabolism between middle- and long-distance runners
Authors: Inaba Takeru , Watanabe Takuya , Morita Yuki , Hatta Hideo 
Published: May 2024

It is important for runners and coaches to figure out the characteristics of lactate metabolism in terms of planning the proper training. This study investigated the differences in lactate production and oxidation capacities between middle- and long-distance runners by using blood lactate concentration. We hypothesized that long-distance runners have greater capacity to oxidize lactate and middle-distance runners have greater capacity to produce lactate. In this study, 14 middle- and 14 long-distance male runners performed a multi-stage incremental test until exhaustion. Each running stage was 3-minute with 1-minute rest between stages. Blood lactate concentration was measured at rest and after each stage, and some metrics associated with runner’s capacity to oxidative lactate during moderate intensity exercise were calculated. The changes in blood lactate concentration measured after the final state of the test were modeled as a biexponential time function to evaluate lactate productive and oxidative capacities after high-intensity exercise. During moderate-intensity exercise, long-distance runners showed significant decrease in blood lactate concentrations during the first few stages of the test compared to rest, indicating greater oxidation of lactate than production of lactate during moderate intensity exercise (p<0.05), while middle distance runners showed slight increase in blood lactate concentrations even for the first several stages. Middle-distance runners showed significantly higher amount of lactate produced (p<0.05) and greater lactate oxidation during high-intensity exercise than those in long-distance runners (p<0.01), suggesting that both lactate production and oxidation of middle-distance runners were greater than those of long-distance runners during high-intensity exercise. These results suggest that characteristics of lactate metabolism in middle- and long-distance runners depend partly on exercise intensity. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Endothelin-1 stimulated human preadipocyte growth through the AMPK, ERK, cJUN, PKC, and STAT3 pathways
Authors: Hsiao Po-Jen , Siao An-Ci , Kuo Chih-Chun , Shih Li-Jane , Kao Yung-Hsi 
Published: May 2024

High level of plasma endothelin (ET)-1 was noticed in obesity, and it was found to regulate adipogenesis and the endocrine activity of fat cells. However, relatively little is known about the ET-1 signaling pathway in preadipocyte growth. Our previous reports have shown that ET-1 and ET-3 stimulated murine 3T3-L1 preadipocyte growth through different kinase signaling cascades with ET type A receptor (ETAR) but not ETBR dependency. In this study, the hypothesis arose that ET-1 may regulate human visceral white preadipocyte growth through the AMPK, ERK, cJUN, PKC, and STAT3 pathways with ET receptor-specific dependency. As indicated by an increased number of cells and greater conversion of 3-4,5-dimethylthiazol-2-yl-2,5 diphenyl tetrazolium bromide (MTT) to formazan crystals by living cells, the stimulation of human preadipocyte growth by ET-1 depended on concentration. Neither ET-2 nor ET-3 stimulated human preadipocyte growth. When signaling pathways were examined, ET-1 signaling stimulated phosphorylation of AMPK, ERK, cJUN, PKC, and STAT3, proteins but not AKT, JNK, or p38 MAPK. Treatment with an ETAR antagonist, such as BQ610, or an ETBR antagonist, such as BQ788, blocked the ET-1-induced increase in cell growth and phosphorylated levels of AMPK, PKC, and STAT3 proteins. However, treatment with BQ788 but not BQ610 blocked the ET-1-increased levels of ERK and c-JUN protein phosphorylation. In addition, pretreatment with specific inhibitors of AMPK (compound C), ERK1/2 (U0126), JNK (SP600125), JAK2/STAT3 (AG490), or PKC (Ro318220) prevented the ET-1-induced increase in cell growth and reduced the ET-1-stimulated phosphorylation of AMPK, ERK1/2, c-JUN, STAT3, and PKC. However, neither the p38 MAPK antagonist nor the ceramide synthase inhibitor altered the effect of ET-1. The results indicate that the target molecules of ETAR and ETBR signaling pathways transducing ET-1 growth signals in human visceral preadipocytes can be similar (e.g., AMPK, JAK2/STAT3, and PKC) or different (e.g., ERK1/2 and JNK/c-JUN). This work was supported in part by the National Science and Technology Council, Taiwan, Grant NSTC 112-2320-B-008-001 to YHK and the Taoyuan Armed Forces General Hospital, Taiwan, Grant AFTGH to PJH, CCK, LJS, and YHK. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
AKAP2 plays a pivotal role in renal acid-base homeostasis during metabolic acidosis
Authors: Belaid Houwayda , Morla Luciana , Wang Dongmei , Van Bemmelen Miguel , Diviani Dario , Crambert Gilles , Staub Olivier 
Published: May 2024

Reversible phosphorylation and dephosphorylation of kidney proteins modulate their activities and localization and play a central role in maintaining fluid and acid-base homeostasis. The proximal tubule and the intercalated cells of the nephron are main sites of acid-base balance. It was previously demonstrated that some kidney transporters involved in the pH homeostasis were regulated by the c-AMP/Protein Kinase A (PKA) signaling pathway.The A-Kinase anchoring protein 2 (AKAP2), is a scaffold protein that binds to the Protein Kinase A (PKA) allowing the phosphorylation of target proteins but is also known to interact with Protein Phosphatase 1 and consequently contributes to protein dephosphorylation. In this study, we hypothesize that AKAP2 regulates the activity and localization of renal transporters during metabolic acidosis. An inducible and nephron-specific Akap2Pax8/LC1 knockout mouse model was generated. Fluorescent immunostaining showed that AKAP2 is present in the tubules mainly at the apical plasma membrane. AKAP2 knock-out mice in normal conditions presented an acidic urine pH and polyuria compared to control mice. Ex-vivo data from micro-perfused CCDs demonstrated a higher Na+ reabsorption and K+ secretion in AKAP2 KO mice. This suggests its importance in maintaining acid-base balance even under physiological conditions. Moreover, when treated with an ammonium chloride diet, KO mice were sensitive to the acid load; showed a lower blood pH, hyperchloremia, a lower bicarbonate level and a two-fold higher blood ammonia. The sensitivity of the KO mice further supports the role of AKAP2 in acid-base homeostasis. Although we think this is due to renal acid-base transporters activity deregulation, the consideration of a potential defect in water reabsorption mechanisms contributing to acidosis is also valid. Our study provides valuable insights into the role of AKAP2 in maintaining fluid and acid-base homeostasis in the kidneys. The findings open avenues for further research into the molecular mechanisms underlying AKAP2-mediated regulation of renal transporters and its impact on acid-base balance. Swiss National Science Foundation (SNSF). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
White Matter Microstructure of the Genu of the Corpus Callosum Measured Using Neurite Orientation Dispersion and Density Imaging (NODDI) Is Associated with Cardiorespiratory Fitness in Older Adults
Authors: Miller Kathleen , Howery Anna J. , Corkery Adam , Loggie Nicole A. , Eldridge Marlowe , Barnes Jill N. 
Published: May 2024

Changes in white matter microstructure of the genu of the corpus callosum are predictive of cognitive decline in patients with mild cognitive impairment. Cardiorespiratory fitness (CRF) is positively associated with brain health; however, the relationship between cardiorespiratory fitness and white matter microstructure of the genu of the corpus callosum is unknown. Further, a novel diffusion method for assessing white matter microstructure, neurite orientation dispersion and density imaging (NODDI), can detect specific microstructural features that are not observed with conventional diffusion tensor imaging (DTI). Young (n=27, age=25±5, m=12, f=15) and older (n=23, age=64±5, m=12, f=11) adults free of underlying disease participated in this study. CRF was assessed using an incremental maximal exercise test on a cycle ergometer. On a separate visit, white matter microstructure of the genu of the corpus callosum was measured using both DTI and NODDI MRI scans. In young adults, there were no associations between CRF and white matter microstructure of the genu of the corpus callosum measured using either DTI or NODDI (p>0.05). In older adults, there were no associations between CRF and white matter microstructure of the genu of the corpus callosum measured with DTI. However, in older adults, there was a positive association between CRF and orientation dispersion index of the genu of the corpus callosum measured with NODDI (r=0.47, p=0.02). In conclusion, using conventional DTI, no associations between CRF and white matter microstructure of the genu of the corpus callosum were observed. However, using NODDI, which can detect specific microstructural features, our results suggest that older adults with higher CRF demonstrated enhanced white matter microstructure, specifically orientation dispersion index, of the genu of the corpus callosum. Conventional DTI may underestimate the impact of CRF on age-related changes in white matter microstructure. National Institutes of Health - HL118154 (JNB), HL007936 (KBM). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.