Biology subjects

Gong, M. C.

Publications and source records attributed to Gong, M. C..

3 recordsLinked to original sources

bioRxiv2024

Exenatide administration time determines the effects on blood pressure dipping in db/db mice via modulation of food intake and sympathetic activity

AbstractType 2 diabetics have an increased prevalence of hypertension and nondipping blood pressure (BP), which worsen cardiovascular outcomes. Exenatide, a short acting glucagon-like peptide-1 receptor agonist (GLP-1RA) used to treat type 2 diabetes, also demonstrates blood pressure (BP)-lowering effects. However, the mechanisms behind this and the impact of administration timing on BP dipping remain unclear. We investigated the effects of exenatide intraperitoneal injected at light onset (ZT0) or dark onset (ZT12) in diabetic (db/db) mice and nondiabetic controls. Using radio-telemetry and BioDAQ cages, we continuously monitored BP and food intake. Db/db mice exhibited non-dipping BP and increased food intake. ZT0 exenatide administration restored BP dipping by specifically lowering light-phase BP, while ZT12 exenatide reversed dipping by lowering dark-phase BP. These effects correlated with altered food intake patterns, and importantly, were abolished when food access was removed. Additionally, urinary norepinephrine excretion, measured by HPLC, was significantly reduced 6 hours post-exenatide at both ZT0 and ZT12, suggesting sympathetic nervous system involvement. Notably, combining exenatide with either ganglionic blocker mecamylamine or -blocker prazosin did not enhance BP reduction beyond the individual effects of each blocker. These findings reveal that exenatide, when administered at light onset, restores BP dipping in db/db mice by suppressing light-phase food intake and sympathetic activity. Importantly, the efficacy of exenatide is dependent on food availability and its timing relative to circadian rhythms, highlighting the potential for chronotherapy in optimizing GLP-1RA- based treatments for type 2 diabetes and hypertension. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=178 HEIGHT=200 SRC="FIGDIR/small/601700v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@29812dorg.highwire.dtl.DTLVardef@dfbaaborg.highwire.dtl.DTLVardef@586343org.highwire.dtl.DTLVardef@dcebe4_HPS_FORMAT_FIGEXP M_FIG C_FIG Article HighlightsO_LIMaintaining a normal blood pressure (BP) circadian rhythm is vital for cardiovascular health, but diabetes often disrupts this rhythm. The effect of exenatide, a GLP-1 receptor agonist (GLP-1RA), on BP rhythm in diabetes is uncertain. C_LIO_LIThis study investigates the impact of exenatide administration timing on BP patterns in diabetic db/db mice. C_LIO_LIFindings indicate that exenatide given at the onset of rest restores normal BP dipping, while at the start of the active phase worsens BP rhythm by modulating food intake and sympathetic activity. C_LIO_LITiming GLP-1 RA administration may optimize BP control and provide cardiovascular benefits for type 2 diabetes patients. C_LI

pharmacology and toxicology↗

bioRxiv2023

Androgen aggravates aortic aneurysms via suppressing PD-1 in mice

Androgen has long been recognized for its pivotal role in the sexual dimorphism of cardiovascular diseases, including aortic aneurysms, a devastating vascular disease with a higher prevalence and mortality rate in men than women. However, the molecular mechanism by which androgen mediates aortic aneurysms is largely unknown. Here, we report that male but not female mice develop aortic aneurysms in response to aldosterone and high salt (Aldo-salt). We demonstrate that both androgen and androgen receptors (AR) are crucial for the sexually dimorphic response to Aldo-salt. We identify T cells expressing programmed cell death protein 1 (PD-1), an immune checkpoint molecule important in immunity and cancer immunotherapy, as a key link between androgen and aortic aneurysms. We show that intraperitoneal injection of anti-PD-1 antibody reinstates Aldo-salt-induced aortic aneurysms in orchiectomized mice. Mechanistically, we demonstrate that AR binds to the PD-1 promoter to suppress its expression in the spleen. Hence, our study reveals an important but unexplored mechanism by which androgen contributes to aortic aneurysms by suppressing PD-1 expression in T cells. Our study also suggests that cancer patients predisposed to the risk factors of aortic aneurysms may be advised to screen for aortic aneurysms during immune checkpoint therapy. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/525073v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@2e8406org.highwire.dtl.DTLVardef@1dde495org.highwire.dtl.DTLVardef@c9f42eorg.highwire.dtl.DTLVardef@be2799_HPS_FORMAT_FIGEXP M_FIG C_FIG

pathology↗

bioRxiv2020

Active Time-Restricted Feeding Protects the Blood Pressure Circadian Rhythm in Diabetic Mice

The quantity and quality of food intake have been considered crucial for peoples wellness. Only recently has it become appreciated that the timing of food intake, independent of total calorie consumption, is also critical. The involvement and contribution of the timing of food intake in nondipping blood pressure (BP), the most common disruption of the BP circadian rhythm in diabetes, however, remains uncertain. Here, we demonstrate that the loss of diurnal rhythm in food intake coincided with nondipping BP in type 2 diabetic db/db mice, and imposing a food intake diurnal rhythm by active time-restricted feeding (ATRF) remarkably prevented db/db mice from the development of nondipping BP. Moreover, ATRF, independent of calorie restriction, also effectively restored the already disrupted BP circadian rhythm in db/db mice. Mechanistically, ATRF reduced the sympathetic vascular tone and BP during the light phase via fasting, thus protecting the BP circadian rhythm in db/db mice. Moreover, we identified BMAL1, an obligatory core clock gene, as a potentially key molecule that links ATRF, sympathetic vascular tone, and BP circadian rhythm. Collectively, these data reveal an important but previously unrecognized role of the timing of food intake in the onset, prevention, and treatment of nondipping BP in diabetes.

physiology↗