Byung-Joon Kim

Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1

Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GLP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express α-gustducin. Ingestion of glucose by α-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from α-gustducin null mice showed markedly defective GLP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses α-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI-H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for α-gustducin. We conclude that L cells of the gut “taste” glucose through the same mechanisms used by taste cells of the tongue. Modulating GLP-1 secretion in gut “taste cells” may provide an important treatment for obesity, diabetes and abnormal gut motility.

Notch signaling in pancreatic endocrine cell and diabetes.

Recent studies have improved our understanding of the physiological function of Notch signaling pathway and now there is compelling evidence demonstrating that Notch is a key regulator of embryonic development and tissue homeostasis. Although further extensive studies are necessary to illustrate the molecular mechanisms, new insights into the role of Notch signaling in pancreas development and diabetes have been achieved. Importantly, the ability to regulate Notch signaling intensity both positively and negatively may have therapeutic relevance for diabetes. Thus, this paper reviews the current knowledge of the roles of Notch signaling in the pancreatic endocrine cell system.

Melatonin attenuates lipopolysaccharide-induced acute lung inflammation in sleep-deprived mice

Abstract:  Sleep disorders are great problems in modern society. Even minimal changes of sleep can affect health. Especially, patients with pulmonary diseases complain of sleep problems such as sleep disturbance and insomnia. Recent studies have shown an association between sleep deprivation (SD) and inflammation, however, the underlying mechanisms remain unclear. In the present study, we investigated whether melatonin protects against acute lung inflammation in SD. Male ICR mice were deprived sleep using modified multiplatform water bath for 3 days. Acute lung inflammation was induced by lipopolysaccharide (LPS; 5 mg/kg). Melatonin (5 mg/kg) and LPS was administered in SD mice at day 2. Mice were divided into five groups as control, SD, LPS, LPS + SD, and LPS + SD + melatonin (each group, n = 11). Mice were killed on day 3 after treatment of melatonin and LPS for 24 hr. Lung tissues were collected for histological examination and protein analysis. The malondialdehyde (MDA) level was determined for the effect of oxidative stress. Melatonin restored weight loss in LPS + SD. Histological findings revealed alveolar damages with inflammatory cell infiltration in LPS + SD. Melatonin remarkably attenuated the alveolar damages. In western blot analysis, LPS reduced the levels of Bcl‐XL and procaspase‐3 in SD mice. After treatment with melatonin, the levels of Bcl‐XL and procaspase‐3 increased when compared with LPS + SD. LPS treatment showed an increase of TUNEL‐positive cells, whereas melatonin prevented the increase of cell death in LPS + SD animals. In lipid peroxidation assay, melatonin significantly reduced the elevated MDA level in LPS + SD. Our results suggest that melatonin attenuates acute lung inflammation during SD via anti‐apoptotic and anti‐oxidative actions.

Circulating concentrations of monocyte chemoattractant protein-1 are associated with menopause status in Korean women.

BACKGROUND Monocyte chemoattractant protein-1 (MCP-1) plays a role in adipose tissue inflammation and insulin resistance. Human circulating MCP-1 concentrations reportedly increase or remain unchanged according to obesity or insulin resistance in various ethnic populations; whether or not circulating MCP-1 concentrations increase after menopause has remained unclear. METHODS We investigated the relationship between circulating MCP-1 concentrations and obesity or insulin resistance, and the relationship between circulating MCP-1 and menopause status in premenopausal (n=111) and postmenopausal (n=64) Korean women. RESULTS Circulating MCP-1 concentrations were significantly higher in postmenopausal women than in obesity-matched premenopausal women; they did not differ between non-obese and obese subgroups of pre- and postmenopausal women. Circulating MCP-1 concentrations had a relationship with menopause status (rho=0.500, p=0.000), irrespective of obesity, but no relationship with obesity or insulin resistance. Circulating MCP-1 concentrations correlated with serum triglycerides (r=0.4, p=0.001) and also correlated with serum triglyceride concentrations, after adjusting for age and obesity, in postmenopausal women. CONCLUSIONS Circulating MCP-1 concentrations are associated with menopause status itself, irrespective of obesity; they do not correlate with obesity or insulin resistance in Korean women, most of whom are not severely obese.

Body Mass Index is Associated with USF1 Haplotype in Korean Premenopausal Women

The upstream stimulatory factor 1 (USF1) gene has been shown to play an essential role as the cause of familial combined hyperlipidemia, and there are several association studies on the relationship between USF1 and metabolic disorders. In this study, we analyzed two single nucleotide polymorphisms in USF1 rs2073653 (306A>G) and rs2516840 (1748C>T) between the case (dyslipidemia or obesity) group and the control group in premenopausal females, postmenopausal females, and males among 275 Korean subjects. We observed a statistically significant difference in the GC haplotype between body mass index (BMI) ≥25 kg/m2 and BMI <25 kg/m2 groups in premenopausal females (χ2=4.23, p=0.04). It seems that the USF1 GC haplotype is associated with BMI in premenopausal Korean females.

Analysis of Differential Expression of Cytochrome P450 Aromatase (Cyp19) in The Efferent Ductules and The Epididymis of Male Rats During Postnatal Development

The present study was performed to determine expression of cytochrome P450 aromatase(Cyp19) in the efferent ductules(EDs) and the epididymis of male rat reproductive tract at different postnatal ages. Total RNAs isolated were reverse-transcribed, and cDNAs were utilized for real-time PCR analysis. In the EDs, the Cyp19 transcript was expressed at all prepubertal ages with the highest level at 14 days of age, but not at 90 days of age. Expression of Cyp19 mRNA in the epididymis was found at all age groups, except 7 days of age. Distinct expression patterns of Cyp19 transcript were shown in each segment of the epididymis. These results indicate that expression of Cyp19 gene in the excurrent duct of male reproductive tract is differentially regulated in age-dependent and segment-specific manners.

EHMTI-0074. Excessive daytime sleepiness in migraineurs is associated with anxiety and depression: a population-based study

Excessive daytime sleepiness is a major clinical and health concern that can have harmful consequences and has shown an associated with anxiety and depression. A close relationship between EDS and migraine has been reported in case-control studies. Case-control study may be affected by confounding factors.

The effect of sleep duration in clinical features and impact of migraine: Result from a population-based study

Results Of 2,836 all participants, 152 were diagnosed as having migraine. The mean sleep duration similar between migraineurs (7.1±1.5 hours) and non-migraine controls (7.1±1.3 hours). Among migraineurs, 15 (9.9%) participants slept iÂ5 hours, 83 (54.6%) slept 5-7 hours, 44 (28.9%) slept 7-9 hours, and 10 (6.6%) slept >9 hours in weekdays. Migraineurs with sleep duration of ≤5 hours reported higher migraine attack frequency (9.8±11.3 attacks per month) comparing to a sleep duration of >5 hours (3.8±6.3 attacks per month, p=0.001). Migraineurs with ≤5 hours sleep duration showed a tendency of increased HIT-6 score (59.7±9.9) comparing to sleep duration of 7-9 hours (53.1±5.8, p=0.088). Unilateral pain was more prevalent among migraineurs with sleep duration of >5 hours comparing to sleep duration of ≤5 hours. Headache severity, pulsating quality, aggravation by movement, nausea, vomiting, photophobia and phonophobia was not significant according to sleep duration.

Excessive daytime sleepiness and migraine: a population-based study.

Results Of 2,836 all participants, 152 (5.1%) were diagnosed as having migraine. EDS was more prevalent among migraineurs comparing to non-migraine controls (25.7% for migraineurs vs. 16.3% for non-migraine controls, p=0.003). Migraineurs with EDS reported higher attack frequency per month (7.0±9.7 attacks for migraineurs vs. 3.5±5.8 for non-migraine controls, p<0.000), higher VAS score for pain intensity (7.1±1.8 for migraineurs vs. 6.0±1.9 for non-migraine controls, p=0.006), and higher HIT-6 score (60.6±10.3 for migraineurs vs. 52.8±8.3 for non-migraine controls, p<0.000) comparing to migraineurs without EDS. Migraineurs with EDS showed more of depression (OR=5.67, 95% CI 2.5-12.7), insomnia (OR=2.98, 95% CI 1.1-8.4) and sleep disordered breathing (OR=2.78, 95% CI 1.1-7.3) than migraineurs without EDS. Unilateral pain, pulsating quality, aggravation by routine physical activity, nausea, vomiting, photophobia and phonophopbia were not significant according to EDS.