Background: The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe. Methods: We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass. Results: In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass. Conclusion This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.

Background/Objectives: Since April 2006, smoking cessation treatment has been included in public health insurance coverage, although conditionally. The tobacco control program usually takes 12 weeks or so. When it comes to the form of treatment, most medical care facilities adopt nicotine replacement therapy (NRT) at their outpatient ward. The cessation success rates are considered not so high as before. In stead of treating nicotine-addict outpatients individually, our hospital has been offering a stop-smoking program all its own since 1999. This study was designed to examine the results of our efforts in the last six years retrospectively.Subjects/Methods: Enrolled for this study were 232 patients who had participated in our six-month smoking cessation program between 1999 and 2005. A non-smokingsupport team made up of a physician, pharmacist(s), nurses, dietitian(s) and physical therapist(s) takes care of groups of participating patients, each group consisting of 10 or less. The patients undergo behavior therapy throughout the 6-month period and NRT in the first eight weeks. Under the program, nutrition guidance is offered regularly by dietitians for weight control and physical exercises by physical therapists for relief from the stress due to abstinence from smoking. We took a questionnaire survey of all the subjects and worked out the ratios of those persons who had remained abstinent up to one year after they stopped smoking to the total.Results: The rates of abstinence maintained eight weeks, six months and one year after the start of cessation were 78.4%, 70.3% and 64.7%, respectively. Of those who were still abstinent, 78.0% replied that they found it easy to resist the urge to smoke cigarette thanks to the smoking cessation program.Conclusion: Our six-month participatory tobacco control program was found effective as high cessation rates were maintained.
Cessation of smoking ; seconds ; month ; week ; Smoking