Electronic Bypass for Diabetes
Electronic Bypass for Diabetes
批准号:
10179364
负责人:
Jiande Chen
金额:
$45.33万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-07-01 至 2023-05-31
关键词:
AccelerationAcuteAffectAlgorithmsAmericanAnimal ModelAnimalsApoptosisB-Cell DevelopmentBeta CellBlood GlucoseBody Weight decreasedBypassCell physiologyCharacteristicsChronicClinicalColonControlled StudyConventional SurgeryDevelopmentDiabetes MellitusDistalEatingElectric StimulationExcisionFastingFoodGLP-I receptorGLUT-2 proteinGastrectomyGastric BypassGastric EmptyingGastric Inhibitory PolypeptideGastrointestinal HormonesGastrointestinal TransitGastroparesisGlucoseGoalsHormonalHormonesHungerHyperglycemiaHypoglycemiaIndividualIngestionInsulinIntestinal AbsorptionIntestinal BypassesIntestinesIslets of LangerhansL CellsMedicalMethodologyMethodsMonitorMorbid ObesityMorphologyMovementNon-Insulin-Dependent Diabetes MellitusNutrientOralPancreasPlasmaPlayPreventionProceduresRattusRegulationRodent ModelRoleSmall IntestinesSpeedStimulusStomachSurfaceSystemTechnologyWeightWireless Technologyalgorithm developmentanalogartificial neural networkbariatric surgerybaseblood glucose regulationcostdesigndiabetic patientdiabetic ratexperimental studyghrelinglucagon-like peptide 1glycemic controlileumimprovedincretin hormoneinsulin secretionnovelobese patientspancreatic islet functionpreventprotective effecttranscription factor
中文摘要
糖尿病影响了超过9%的美国人,2012年在美国的花费超过2450亿美元。最近减肥
英文摘要
Diabetes affects more than 9% of Americans and costs over $245 billion in 2012 in USA. Recently bariatric
surgery, such as Roux-en-Y gastric bypass and sleeve gastrectomy, has been proposed for treating diabetic
patients with obesity due to its hypoglycemic effect on postprandial blood glucose and significant weight loss.
A novel method of intestinal electrical stimulation (IES) is proposed for the treatment of diabetes in this
application. In this method, IES is designed to alter gastrointestinal transit and hormones, including incretin
hormones, such as glucagon like peptide-1 (GLP-1). Our preliminary studies have demonstrated acceleration
of intestinal transit, an increase in postprandial GLP-1 and a reduction in blood glucose after oral glucose.
Chronically, the proposed IES has resulted in improvement in glycemic control and improvement in pancreatic
islets functions. According to these findings, we hypothesize that the acute hypoglycemic effect of IES in the
postprandial state is attributed to IES-induced enhancement in the release of GLP-1 and possibly other
hormones as well, such as ghrelin, and that the chronic hypoglycemic effect of IES in both fasting and fed
states is attributed to improvement in beta-cell functions, attributed to the prevention of the detrimental effects
of hyperglycemia and the ameliorating effect of IES-induced elevated GLP-1 on beta-cell functions.
The project will be performed using advanced technologies (wireless stimulation and recording cages, and
autonomic and continuous food intake monitoring) that allow IES to be conducted in freely moving animals.
The best characterized animal model of spontaneous Type 2 diabetes, the Goto-Kakizaki (GK) rat will be used
to accomplish following specific aims: 1) To optimize IES parameters, develop on-demand IES and perform
closed-loop IES. First, we will systematically optimized stimulation parameters to maximize the hypoglycemic
effect of IES. Then we will develop an algorithm to automatically detect food intake and then trigger IES upon
food ingestion. It will be based on characteristics of intrinsic intestinal myoelectrical activity and artificial neural
network. The meal triggered IES will avoid excessive stimulation. Finally, a closed-loop IES method (each
stimulus is synchronized with intrinsic intestinal myoelectrical activity) will be developed to further increase the
efficacy of IES for diabetes. 2) To study the hypoglycemic mechanisms of acute IES involving incretin
hormones, such as GLP-1, and ghrelin, and the intestinal transit mechanisms involved in the IES-induced
elevation of insulin-stimulating gastrointestinal hormones. 3) To explore cellular mechanisms of chronic IES on
long-term glycemic control. Chronic IES will be performed to investigate long-term hypoglycemic effects of IES
in both fasting and fed states, and mechanisms involving pancreatic islets functions, beta-cell apoptosis and
proliferation, and a number of transcription factors involved in the regulation of β-cell development,
differentiation and function. Possible involvement of L-cells in the distal gut will also be investigated.
期刊论文(4)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1007/s11517-023-02832-z
发表时间:
2023-09
期刊:
Medical & biological engineering & computing
影响因子:
3.2
作者:
[]
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