Glucagon-like peptide-1 and impaired counterregulatory responses to hypoglycemia in type 1 diabetes

This letter comments on a study by Jin et al,published recently in the World Journal of Diabetes.Hypoglycemia is a significant complication of diabetes,with primary defense mechanisms involving the stimulation of glucagon secretion inα-cells and the inhibition of insulin secretion in pancreaticβ-cells,which are often compromised in type 1 diabetes mellitus(T1DM)and advanced type 2 diabetes mellitus.Recurrent hypoglycemia predisposes the development of impaired hypoglycemia awareness,a condition underpinned by complex pathophysiological processes,encompassing central nervous system adaptations and several hormonal interactions,including a potential role for glucagon-like peptide-1(GLP-1)in paracrine and endocrine vias.Experimental evidence indicates that GLP-1 may impair hypoglycemic counterregulation by disrupting the sympathoadrenal system and promoting somatostatin release in pancreaticδ-cells,which inhibits glucagon secretion from neighboringα-cells.However,current trials evaluating GLP-1 receptor agonists(GLP-1 RAs)in T1DM patients have shown promising benefits in reducing insulin requirements and body weight,without increasing the risk of hypoglycemia.Further research is essential to elucidate the specific roles of GLP-1 and GLP-1 RAs in modulating glucagon secretion and the sympathetic-adrenal reflex,and their impact on hypoglycemia unawareness in T1DM patients.

Investigating the impact of intestinal glucagon-like peptide-1 on hypoglycemia in type 1 diabetes

Recent advances in understanding type 1 diabetes(T1D)highlight the complexity of managing hypoglycemia,a frequent and perilous complication of diabetes therapy.This letter delves into a novel study by Jin et al,which elucidates the role of intestinal glucagon-like peptide-1(GLP-1)in the counterregulatory response to hypoglycemia in T1D models.The study employed immunofluorescence,Western blotting,and enzyme-linked immunosorbent assay to track changes in GLP-1 and its receptor expression in diabetic mice subjected to recurrent hypoglycemic episodes.Findings indicate a significant increase in intestinal GLP-1 and GLP-1 receptor expression,correlating with diminished adrenal and glucagon responses,crucial for glucose stabilization during hypoglycemic events.This letter aims to explore the implications of these findings for future therapeutic strategies and the broader understanding of T1D management.

Clinical profile and risk factors of symptomatic and asymptomatic hypoglycemia in neonates admitted to NICU in a tertiary care center: A cross-sectional study

Objective:To investigate the clinical profile and risk factors of symptomatic and asymptomatic hypoglycemia in neonates admitted to a neonatal intensive care unit in a tertiary care center.Methods:The prospective observational study was conducted in a tertiary care center in the Specialty Department of Pediatric.196 Newborn babies with blood glucose levels<45 mg/dL were examined with a simple random sampling method between December 2019 and November 2021.Maternal and neonatal risk factors and clinical signs were recorded and compared between symptomatic and asymptomatic cases.Results:The proportion of symptomatic hypoglycemia neonates born to gestational diabetes mellitus mothers was significantly higher(23.4%vs.8.4%)(P<0.05).Small for gestational age,low birth weight,respiratory distress syndrome,hypothermia,and endocrine disorders were risk factors.The death rate in asymptomatic hypoglycemia neonates was significantly higher(58%vs.39%)(P<0.05).Conclusions:The study indicates that maternal gestational diabetes mellitus is associated with symptomatic hypoglycemia and asymptomatic hypoglycemia is associated with neonatal mortality.It is important to take vigilance and timely interventions to address associated symptoms,particularly poor feeding,in the management of neonatal hypoglycemia.

Efficacy of Raw Corn Starch in Insulinoma-Related Hypoglycemia:A Promising Supportive Therapy

Objective To investigate the efficacy of raw corn starch(RCS)in clinical management of insulinoma-induced hypoglycemia.Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively,and analyzed the therapeutic effects of the RCS intervention on blood glucose control,weight change,and its adverse events.Results The study population consisted of 24 cases of insulinoma patients,7 males and 17 females,aged 46.08±14.15 years.Before RCS-supplemented diet,all patients had frequent hypoglycemic episodes(2.51±3.88 times/week),concurrent with neuroglycopenia(in 83.3% of patients)and autonomic manifestations(in 75.0% of patients),with the median fasting blood glucose(FBG)of 2.70(interquartile range[IQR]:2.50-2.90)mmol/L.The patients'weight increased by 0.38(IQR:0.05-0.65)kg per month,with 8(33.3%)cases developing overweight and 7(29.2%)cases developing obesity.All patients maintained the RCS-supplemented diet until they underwent tumor resection(23 cases)and transarterial chemoembolization for liver metastases(1 case).For 19 patients receiving RCS throughout the day,the median FBG within one week of nutritional management was 4.30(IQR:3.30-5.70)mmol/L,which was a significant increase compared to pre-nutritional level[2.25(IQR:1.60-2.90)mmol/L;P<0.001].Of them,10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment[3.20(IQR:2.60-3.95)mmol/L vs.2.15(IQR:1.83-2.33)mmol/L;P<0.001].Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management[3.50(IQR:2.50-3.65)mmol/L vs.2.20(IQR:1.80-2.60)mmol/L;P<0.001],but only one patient who continued to receive RCS for over four weeks did not have a significant improvement in FBG.No improvement in weight gain was observed upon RCS supplementation.Mild diarrhea(2 cases)and flatulence(1 case)occurred,and were relieved by reduction of RCS dose.Conclusion The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.

Successful management of severe hypoglycemia induced by total parenteral nutrition in patients with hepatocellular injury: Three cases reports

BACKGROUND Glucose imbalance is common in total parenteral nutrition(TPN).Hypoglycemia seems to be less frequent than hyperglycemia,but it influences the clinical outcome to a greater extent.Therefore,it should be effectively prevented and treated.However,there is no relevant report on how to treat hypoglycemia caused by TPN in patients with liver cell injury.CASE SUMMARY We present three patients with liver cell injury who developed severe hypo-glycemia during or after TPN infusion.The causes of severe hypoglycemia and glucose-raising strategies were discussed.According to the physiological charac-teristics of the hepatocellular injury,the ratio of nutrition components prescribed in TPN was appropriately adjusted for the three cases.We simultaneously reduced the dose of insulin and fat emulsion,and increased the dose of glucose in TPN.The blood glucose level was restored to normal range and clinical symptoms were eliminated.CONCLUSION When hypoglycemia occurs during or after TPN in patients with hepatocellular injury,physicians need to simultaneously reduce insulin and fat emulsion,and increase glucose,and correct severe hypoglycemia in time to reduce its adverse consequences.

Glucagon-like peptide-1 agonists:Role of the gut in hypoglycemia unawareness,and the rationale in type 1 diabetes

Type 1 diabetes is increasing and the majority of patients have poor glycemic control.Although advanced technology and nanoparticle use have greatly enhanced insulin delivery and glucose monitoring,weight gain and hypoglycemia remain major challenges and a constant source of concern for patients with type 1 diabetes.Type 1 diabetes shares some pathophysiology with type 2 diabetes,and an overlap has been reported.The above observation created great interest in glucagon-like peptide-1 receptor agonists(GLP-1)as adjuvants for type 1 diabetes.Previous trials confirmed the positive influence of GLP-1 agonists onβcell function.However,hypoglycemia unawareness and dysregulated glucagon response have been previously reported in patients with recurrent hypoglycemia using GLP-1 agonists.Jin et al found that the source of glucagon dysregulation due to GLP-1 agonists resides in the gut.Plausible explanations could be gut nervous system dysregulation or gut microbiota disruption.This review evaluates the potential of GLP-1 agonists in managing type 1 diabetes,particularly focusing on their impact on glycemic control,weight management,and glucagon dysregulation.We provide a broader insight into the problem of type 1 diabetes mellitus management in the light of recent findings and provide future research directions.

Role of intestinal glucagon-like peptide-1 in hypoglycemia response impairment in type 1 diabetes

This study critically examines the novel findings presented by Jin et al,which explores the role of intestinal glucagon-like peptide-1(GLP-1)in impaired counterregulatory responses to hypoglycemia in mice with type 1 diabetes.The study identifies intestinal GLP-1 as a significant determinant in the physiological responses to hypoglycemia,offering new insights into its potential implications for diabetes management.The editorial synthesizes these findings,discusses their relevance in the context of current diabetes research,and outlines potential avenues for future investigation of intestinal GLP-1 as a therapeutic target.This analysis underscores the need for continued research into the complex mechanisms underlying impaired hypoglycemia responses and highlights the potential of targeting intestinal GLP-1 pathways in therapeutic strategies for type 1 diabetes.

Role of intestinal glucagon-like peptide-1 in impaired counterregulatory responses to hypoglycemia

Patients with type 1 diabetes mellitus(T1DM)experience multiple episodes of hypoglycemia,resulting in dysfunctional counter-regulatory responses with time.The recent experimental study by Jin et al explored the role of intestinal glucagon-like peptide-1(GLP-1)in impaired counter-regulatory responses to hypoglycemia.They identified intestinal GLP-1 along with GLP-1 receptor(GLP-1R)as the new key players linked with impaired counter-regulatory responses to hypoglycemia in type 1 diabetic mice.They also demonstrated that excessive expression of GLP-1 and GLP-1R was associated with attenuated sympathoadrenal responses and decreased glucagon secretion.The study has enormous clinical relevance as de-fective counter regulation and hypoglycemia unawareness negatively impacts the intensive glycemic management approach in this group of patients.However,the physiological processes must be validated in dedicated human studies to compre-hensively understand the pathophysiology of this complex relationship,and to clarify the true extent of impaired hypoglycemia counter regulation by intestinal GLP-1.For now,following the results of the index study and other similar studies,GLP-1 analogues usage in T1DM must be carefully monitored,as there is an inherent risk of worsening the already impaired counter-regulatory responses in these patients.Further studies in the future could identify other key players in-volved in this clinically relevant interaction.

Relationship between hemoglobin glycation index and risk of hypoglycemia in type 2 diabetes with time-in-range in target

BACKGROUND In patients with type 2 diabetes mellitus(T2DM),the risk of hypoglycemia also occurs in at a time-in-range(TIR)of>70%.The hemoglobin glycation index(HGI)is considered the best single factor for predicting hypoglycemia,and offers new perspectives for the individualized treatment of patients with well-controlled blood glucose levels that are easily ignored in clinical settings.All participants underwent a 7-days continuous glucose monitoring(CGM)using a retrospective CGM system.We obtained glycemic variability indices using the CGM system.We defined HGI as laboratory hemoglobin A1c minus the glucose management indicator.Patients were categorized into low HGI(HGI<0.5)and high HGI groups(HGI≥0.5)according to HGI median(0.5).Logistic regression and receiver operating characteristic curve analyses were used to determine the risk factors for hypoglycemia.RESULTS We included 129 subjects with T2DM(54.84±12.56 years,46%male)in the study.Median TIR score was 90%.The high HGI group exhibited lower TIR and greater time below range with higher hemoglobin A1c than the low HGI group;this suggests more glycemic excursions and an increased incidence of hypoglycemia in the high HGI group.Multivariate analyses revealed that mean blood glucose,standard deviation of blood glucose and HGI were independent risk factors for hypoglycemia.Receiver operating characteristic curve analysis indicated that the HGI was the best predictor of hypoglycemia.In addition,the optimal cut-off points for HGI,mean blood glucose,and standard deviation of blood glucose in predicting hypoglycemia were 0.5%,7.2 mmol/L and 1.4 mmol/L respectively.CONCLUSION High HGI was significantly associated with greater glycemic excursions and increased hypoglycemia in patients with TIR>70%.Our findings indicate that HGI is a reliable predictor of hypoglycemia in this population.

妊娠期糖尿病患者分娩前糖化血红蛋白控制水平对大于胎龄儿、新生儿低血糖发生风险的影响

目的探讨妊娠期糖尿病(GDM)患者分娩前糖化血红蛋白(HbA1c)控制水平对大于胎龄儿(LGA)、新生儿低血糖发生风险的影响。方法回顾分析2020年4月至2023年5月收治的172例GDM患者及其新生儿的临床资料。根据分娩前1周GDM患者HbA1c检测值,将172例患者分为A组60例(HbA1c<6.0%)、B组81例(HbA1c 6.0%~<7.0%)、C组31例(HbA1c≥7.0%)。收集3组GDM患者及新生儿基线资料,比较3组LGA、新生儿低血糖发生情况,并采用多因素logistic回归模型分析GDM患者分娩前不同HbA1c控制水平与LGA、新生儿低血糖的关系。结果3组孕妇空腹血糖、新生儿出生体质量及新生儿1 min Apgar评分比较:A组<B组<C组(P<0.05);3组新生儿初始血糖值比较:A组>B组>C组(P<0.05)。3组LGA、新生儿低血糖发生率比较:A组<B组<C组(P<0.05)。多因素logistic回归分析显示,GDM患者分娩前HbA1c水平6.0%~<7.0%、≥7.0%是导致LGA、新生儿低血糖发生的独立危险因素(P<0.01),且较HbA1c<6.0%的GDM患者LGA发生风险分别增加了1.644、2.124倍,新生儿低血糖发生风险分别增加了1.650、2.045倍。结论GDM患者分娩前HbA1c水平与新生儿体质量、血糖存在紧密联系,孕期对GDM患者HbA1c水平进行积极有效干预,使其达到理想目标值,可有效降低LGA、新生儿低血糖的发生风险。

1例妊娠期急性脂肪肝继发严重凝血功能障碍患者围术期的急救护理

总结妊娠期急性脂肪肝继发严重凝血功能障碍患者围术期急救护理体会。护理要点包括早期识别妊娠期急性脂肪肝,建立多学科快速反应团队;纠正凝血功能障碍,维持内环境稳定;动态评估病情变化,积极预防与处理术后并发症;给予贯穿全程的心理护理、个性化生活支持,做好母乳喂养指导及出院随访护理。经过多学科团队的积极治疗与精细化护理,患者救治成功,顺利出院。随访6个月,母婴状况良好。

围产期优质整体护理在GDM患者中的应用

目的:探讨围产期优质整体护理在妊娠期糖尿病(GDM)患者中的应用。方法:选取2022年1月—2024年1月厦门大学附属妇女儿童医院收治的70例GDM患者。根据随机数表法将其分为对照组和研究组,各35例。对照组给予常规围产期护理,研究组在对照组的基础上给予围产期优质整体护理。比较两组护理前后自我管理能力,新生儿出生后的0.5 h、1 h、2 h及3 h新生儿血糖水平,新生儿低血糖情况及护理满意度。结果:护理后,两组糖尿病自我管理行为量表(SDSCA)评分升高,研究组SDSCA评分高于对照组,差异有统计学意义(P<0.05)。新生儿出生后1 h、2 h、3 h,研究组血糖高于对照组,差异有统计学意义(P<0.05)。新生儿出生后的30 min,研究组新生儿低血糖发生率低于对照组,差异有统计学意义(P<0.05)。研究组护理总满意度高于对照组,差异有统计学意义(P<0.05)。结论:针对GDM孕妇,围产期优质整体护理具有较好的效果,有利于提高患者的自我管理能力,改善患者的血糖水平,降低新生儿低血糖发生率,提高护理满意度。

慢加急性肝衰竭病人低血糖发生风险评估模型的构建与验证研究

目的:构建慢加急性肝衰竭病人低血糖发生风险评估模型,并验证其效果。方法:采用便利抽样法从上海交通大学医学院附属仁济医院2021年1月—2022年12月、2023年1月—5月两阶段收治的慢加急性肝衰竭病人200例、50例,分别设为建模集、验证集,统计建模集发生低血糖的病人例数,筛选慢加急性肝衰竭病人发生低血糖的危险因素,并构建慢加急性肝衰竭病人低血糖发生风险评估模型,检验其预测效果。结果:结果显示,共有31例病人发生低血糖,单因素、多因素Logistic回归分析显示,慢加急性肝衰竭病人发生低血糖的独立危险因素有糖化血红蛋白(HbA1c)水平、合并肝硬化、合并糖尿病、住院时间>27 d、低血糖风险宣教缺失(P<0.05);根据回归分析结果构建低血糖风险评估模型,模型预测慢加急性肝衰竭病人发生低血糖的ROC曲线下面积为0.876,[95%CI(0.844,0.908)],最佳截断值为1.028,灵敏度、特异度分别为0.827,0.844,约登指数为0.671;模型预测准确率为86.00%,灵敏度、特异度分别为0.750,0.947,Kappa系数为0.718。结论:慢加急性肝衰竭病人发生低血糖的危险因素复杂,而HbA1c水平对慢加急性肝衰竭病人低血糖风险有预测价值,临床应加强慢加急性肝衰竭病人HbA1c水平的监测,以期为低血糖风险预防提供依据。

Mechanisms of hypoglycemia unawareness and implications in diabetic patients

Hypoglycemia unawareness(HU) is defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms.It is a major limitation to achieving tight diabetes and reduced quality of life.HU occurs in approximately 40% of people with type 1 diabetesmellitus(T1DM) and with less frequency in T2 DM.Though the aetiology of HU is multifactorial,possible mechanisms include chronic exposure to low blood glucose,antecedent hypoglycaemia,recurrent severe hypoglycaemia and the failure of counter-regulatory hormones.Clinically it manifests as the inability to recognise impeding hypoglycaemia by symptoms,but the mechanisms and mediators remain largely unknown.Prevention and management of HU is complex,and can only be achieved by a multifactorial intervention of clinical care and structured patient education by the diabetes team.Less know regarding the impact of medications on the development or recognition of this condition in patients with diabetes.Several medications are thought to worsen or promote HU,whereas others may have an attenuating effect on the problem.This article reviews recent advances in how the brain senses and responds to hypoglycaemia,novel mechanisms by which people with insulin-treated diabetes develop HU and impaired counter-regulatory responses.The consequences that HU has on the person with diabetes and their family are also described.Finally,it examines the evidence for prevention and treatment of HU,and summarizes the effects of medications that may influence it.

Effect of Recurrent Severe Hypoglycemia on Cognitive Performance in Adult Patients with Diabetes: A Meta-analysis

The purpose of this study was to investigate the existence and extent of cognitive impairment in adult diabetes mellitus（DM） patients with episodes of recurrent severe hypoglycemia, by using meta-analysis to synthesize data across studies. PubMed, EMBASE and Cochrane library search engines were used to identify studies on cognitive performance in DM patients with recurrent severe hypoglycemia.Random-effects meta-analysis was performed on seven eligible studies using an inverse-variance method. Effect sizes, which are the standardized differences between the experimental group and the control group, were calculated. Of the 853 studies, 7 studies met the inclusion criteria. Compared with control subjects, the adult DM patients with episodes of recurrent severe hypoglycemia demonstrated a significantly lowered performance on memory in both types of DM patients, and poor performance of processing speed in type 2 DM patients. There was no significant difference between adult DM patients with and those without severe hypoglycemia in other cognitive domains such as general intelligence,executive function, processing speed and psychomotor efficiency. Our results seem to confirm the hypothesis that cognitive dysfunction is characterized by worse memory and processing speed in adult DM patients with a history of recurrent severe hypoglycemia, whereas general intelligence, executive function,and psychomotor efficiency are spared.

Case report on an infant presenting with hypoglycemia,and milky serum

A 4-month-old male baby who presented in a moribund condition with seizures was found to have hepatomegaly,hypoglycemia and milky serum.Serum triglycerides were markedly elevated(3168 mg/dL) with cholesterol being 257 mg/dL and high density lipoprotein levels were low(19 mg/dL).The possibility of glycogen storage disease type Ⅰ was considered in the diagnosis.Infants with glycogen storage disease type Ⅰ may present like sepsis.The association of hepatomegaly, hypoglycemia and abnormal lipid profile stated above should alert the physician to consider glycogen storage disease type Ⅰ in the diagnosis.

Predictors of hypoglycemia in insulin-treated patients with type 2 diabetes mellitus in Basrah

AIM To measure the incidence and determinants(predictors) of hypoglycemia among patients with type 2 diabetes mellitus(T2DM) who were on insulin treatment for at least one year. METHODS The present study is an out-patients based inquiry about the risk and predictors of hypoglycemia among patients with T2DM seeking care at the Al-Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah over a period of 7 mo(from 15^(th) of April, 2013 to 15^(th) of October, 2013). The data used in the study were based on all detailed interview and selected laboratory investigations. A total of 336 patients could be included in the study.RESULTS The incidence of overall hypoglycemia among the studied patients was 75.3% within the last 3 mo preceding the interview. The incidence of hypoglycemia subtypes were 10.2% for severe hypoglycemia requiring medical assistance in the hospital, 44.36% for severe hypoglycemia treated at home by family; this includes both confirmed severe hypoglycemia with an incidence rate of 14.6% and unconfirmed severe hypoglycemia for which incidence rate was 29.76%. Regarding mild self-treated hypoglycemia, the incidence of confirmed mild hypoglycemia was 21.42%, for unconfirmed mildhypoglycemia the incidence rate was 50.0% and for total mild hypoglycemia, the incidence rate was 71.42%. The most important predictors of hypoglycemia were a peripheral residence, increasing knowledge of hypoglycemia symptoms, in availability and increasing frequency of self-monitoring blood glucose, the presence of peripheral neuropathy, higher diastolic blood pressure, and lower Hemoglobin A1c.CONCLUSION Hypoglycemia is very common among insulin-treated patients with T2DM in Basrah. It was possible to identify some important predictors of hypoglycemia.

Causative anti-diabetic drugs and the underlying clinical factors for hypoglycemia in patients with diabetes

Recent clinical trials indicated that the intensive glycemic control do not reduce cardiovascular disease mortality among diabetic patients, challenging a significance of the strict glycemic control in diabetes management. Furthermore, retrospective analysis of the Action to Control Cardiovascular Risk in Diabetes study demonstrated a significant association betweenhypoglycemia and mortality. Here, we systematically reviewed the drug-induced hypoglycemia, and also the underlying clinical factors for hypoglycemia in patients with diabetes. The sulfonylurea use is significantly associated with severe hypoglycemia in patients with type 2 diabetes. The use of biguanide(approximately 45%-76%) and thiazolidinediones(approximately 15%-34%) are also highly associated with the development of severe hypoglycemia. In patients treated with insulin, the intensified insulin therapy is more frequently associated with severe hypoglycemia than the conventional insulin therapy and continuous subcutaneous insulin infusion. Among the underlying clinical factors for development of severe hypoglycemia, low socioeconomic status, aging, longer duration of diabetes, high Hb A1 c and low body mass index, comorbidities are precipitating factors for severe hypoglycemia. Poor cognitive and mental functions are also associated with severe hypoglycemia.

Hypoglycemia in diabetes:An update on pathophysiology,treatment,and prevention

Hypoglycemia is a common complication in patients with diabetes,mainly in those treated with insulin,sulfonylurea,or glinide.Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia.Episodes of hypoglycemia are associated with physical and psychological morbidity.The fear of hypoglycemia constitutes a barrier that impairs the patient’s ability to reach good glycemic control.To prevent hypoglycemia,much effort must be invested in patient education regarding risk factors,warning signs,and treatment of hypoglycemia at an early stage,together with setting personalized goals for glycemic control.In this review,we present a comprehensive update on the treatment and prevention of hypoglycemia in type 1 and type 2 diabetic patients.

EFFECTS OF ACUTE HYPOGLYCEMIA ON THE OREXIN SYSTEM IN RAT

Objective To evaluate the effects of acute glucose level changes on expression of prepro-orexin, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) mRNA in rat hypothalamus tissue and pancreatic islets cells. Methods Thirty adult male Wistar rats were randomly divided into three equal groups (n = 10). The acute hypoglycemia rat model was induced by a single subcutaneous injection of insulin. Twenty acute hypoglycemia rats were divided into group B and group C. Group B was allowed to eat freely, while group C was food-deprived. Control rats were injected the same volume of saline. The effect of glucose levels (2.8 mmol/L and 8.3 mmol/L) on pancreatic islet cell orexin system was detected in pancreas islet cell cultured in vitro. The expression of prepro-orexin and OXR mRNA was examined in rat hypothalamus tissue and pancreatic islets cell cultured in vitro using reverse transcription-polymerase chain reaction (RT-PCR). Results Expression of orexin mRNA increased about 150% for the food-deprived hypoglycemia rats in comparison with control group (P < 0.01), whereas expression of OX1R mRNA decreased up to 30% (P < 0.01). However, expression of OX2R mRNA was unchanged in comparison with control group. In vitro, after incubation with 2.8 mmol/L glucose for 6 hours, the expression of prepro-orexin mRNA increased 2 times in rat pancreas islet cells in comparison with 8.3 mmol/L glucose group (P < 0.01). But the expression of OX1R mRNA was not sensitive to acute glucose fluctuation.Conclusions Orexin in rat hypothalamus is stimulated by decline in blood glucose and inhibited by signals related to feeding. Moreover, glucose plays a role in modulating the gene expression of prepro-orexin in rat pancreatic islet cells.