Functionalized Cycloolefin Ligand as a Solution to Ortho-Constraint in the Catellani-Type Reaction.

The Catellani reaction, i.e., the Pd/norbornene (NBE) catalysis, has been evolved into a versatile approach to multisubstituted arenes via the ortho-functionalization/ipso-termination process of a haloarene. Despite significant advances over the past 25 years, this reaction still suffered from an intrinsic limitation in the substitution pattern of haloarene, referred to as "ortho-constraint". When an ortho substituent is absent, the substrate often fails to undergo an effective mono ortho-functionalization process, and either ortho-difunctionalization products or NBE-embedded byproducts predominate. To tackle this challenge, structurally modified NBEs (smNBEs) have been developed, which were proved effective for the mono ortho-aminative, -acylative, and -arylative Catellani reactions of ortho-unsubstituted haloarenes. However, this strategy is incompetent for solving the ortho-constraint in Catellani reactions with ortho-alkylation, and to date there lacks a general solution to this challenging but synthetically useful transformation. Recently, our group developed the Pd/olefin catalysis, in which an unstrained cycloolefin ligand served as a covalent catalytic module to enable the ortho-alkylative Catellani reaction without NBE. In this work, we show that this chemistry could afford a new solution to ortho-constraint in the Catellani reaction. A functionalized cycloolefin ligand bearing an amide group as the internal base was designed, which allowed for mono ortho-alkylative Catellani reaction of iodoarenes suffering from ortho-constraint before. Mechanistic study revealed that this ligand is capable of both accelerating the C-H activation and inhibiting side reactions, which accounts for its superior performance. The present work showcased the uniqueness of the Pd/olefin catalysis as well as the power of rational ligand design in metal catalysis.

The Dynamics of Circulating Monocyte Subsets and Intra-Plaque Proliferating Macrophages during the Development of Atherosclerosis in ApoE-/- Mice.

To detect the development of monocytes and proliferative macrophages in atherosclerosis of ApoE-/- mice, we randomly assigned 84 ApoE-/- mice fed western diet or chow diet. On weeks 2, 4, 6, 8, 10, and 12 after fed high-fat diet or normal chow diet, animals were euthanized (n = 7 for each group at each time point). Flow cytometry methods were used to analyze the proportions of circulation monocyte subsets. The macrophage and proliferative macrophage accumulation within atherosclerotic plaques was estimated by confocal florescence microscopy. Plasma levels of total cholesterol and triglyceride were measured by ELISA kit. The plaques of aortic sinus were stained with Oil Red O. The percent of Ly6Chi circulation monocyte, the density of proliferation macrophage, the total plasma cholesterol and triglyceride levels, the lesion area of ApoE-/- mice were consistently elevated in chow diet throughout the trial. The total plasma cholesterol and triglyceride levels, the lesion area were elevated in western diet group with age, and they were always higher than the chow diet group. The Ly6Chi monocytes and proliferative macrophages reached a plateau at 8 weeks and 6 weeks; despite continued high-triglyceride high-cholesterol diet the percent did not significantly change. Interestingly, the density of macrophage did not change significantly over age in western and chow diet groups. Our results provide a dynamic view of Ly6Chi monocyte subset, the density of macrophage and proliferation macrophage change during the development and progression of atherosclerosis, which is relevant for designing new treatment strategies targeting mononuclear phagocytes in this model.

[Nonalcoholic Fatty Liver Disease and Weight Loss].

Nonalcoholic fatty liver disease(NAFLD)refers to hepatic steatosis without other known causes such as alcohol abuse or hepatic virus infection. NAFLD has become a chronic disease worldwide,and its prevalence is constantly growing. Hepatic insulin resistance caused by obesity results in the deposition of triglycerides in the liver,promoting the occurrence and development of NAFLD. Weight loss is the only safe and effective method for NAFLD. Lifestyle intervention plays a cornerstone role in treating NAFLD;however,most patients can not achieve and maintain the ideal body weight by lifestyle intervention alone. Glucagon-like peptide-1 receptor agonist and metabolic surgery are promising treatments for NAFLD.

Clinical Characteristics of 261 Cases of Hospitalized Patients with Type 1 Diabetes Mellitus.

Objective To retrospectively analyze the clinical characteristics of 261 cases of hospitalized patients with type 1 diabetes mellitus (T1DM) in Peking Union Medical College Hospital (PUMCH).Methods Clinical data of 261 cases of hospitalized patients diagnosed with T1DM in the Department of Endocrinology at PUMCH from January 2007 to December 2014 were analyzed retrospectively. All patients were divided into the T1DM antibodies positive group (n=180) and negative group (n=81) according to the results of immunohistochemistry, in which 123 newly diagnosed T1DM patients were divided into the adult onset group (>18 years, n=58) and non-adult onset group (≤18 years, n=65) according to the onset age of T1DM, respectively. The clinical characteristics from different groups were compared.Results In 261 patients, the average age was 26.6±15.4 years, the average disease duration was 49 (1-480) months, the positive rate of antibodies to glutamic acid decarboxylase antibody was 58.8% (153/260). The level of 2-hour postprandial C peptide and the positive rate of T1DM antibodies in the non-adult onset group were higher than those in the adult onset group (0.98 vs. 0.52 ng/ml, P=0.002 and 80.4% vs. 62.5%, P=0.048). The age of onset in the T1DM antibodies positive group was smaller than that in the T1DM antibodies negative group (19.7±11.4 vs. 24.7±15.6 years, P=0.04), while the incidence of ketosis in the T1DM antibodies positive group was higher than that in the T1DM antibodies negative group (48.3% vs. 34.2%, P=0.035). With the progress of the disease, the fasting C peptide level of the T1DM antibodies positive group decreased more rapidly. Compared with the single time hospitalized patients, multiple hospitalized patients had a lower incidence of diabetic retinopathy (8.2% vs. 22.4%, P=0.032), a lower hemoglobin A1c level (8.04%±2.10% vs. 9.56%±2.64%, P<0.001) and fasting blood glucose level (8.7±3.1 vs. 10.9±4.2 mmol/L, P<0.001).Conclusions Compared with the non-adult onset T1DM patients, the islet function of adult onset patients was even worse. In the T1DM antibodies positive patients, the islet ß cell function decreased more rapidly, so the antibodies could not only clarify the diagnosis of T1DM and also predict prognosis of the islet ß cell function. In the management of T1DM patients, regular hospital revisits contributed to get better glycemic control and reduced the occurrence of diabetic complications.

Analysis of association among clinical features and shorter leukocyte telomere length in mitochondrial diabetes with m.3243A>G mitochondrial DNA mutation.

BACKGROUND: Mitochondrial diabetes is a kind of rare diabetes caused by monogenic mutation in mitochondria. The study aimed to summarize the clinical phenotype profiles in mitochondrial diabetes with m.3243 A>G mitochondrial DNA mutation and to investigate the mechanism in this kind of diabetes by analyzing the relationship among clinical phenotypes and peripheral leukocyte DNA telomere length. METHODS: Fifteen patients with maternally inherited diabetes in five families were confirmed as carrying the m.3243 A>G mitochondrial DNA mutation. One hundred patients with type 2 diabetes and one hundred healthy control subjects were recruited to participate in the study. Sanger sequencing was used to detect the m.3243 A>G mitochondrial DNA mutation. The peak height G/A ratio in the sequence diagram was calculated. Real-time polymerase chain reaction (PCR) was used to measure telomere length. RESULTS: The patients with mitochondrial diabetes all had definite maternally inherited history, normal BMI (19.5 ± 2.36 kg/m(2)), early onset of diabetes (35.0 ± 14.6 years) and deafness. The peak height G/A ratio correlated significantly and negatively with the age at onset of diabetes (≦ 25 years, 61.6 ± 20.17%; 25-45 years, 16.59 ± 8.64%; >45 years, 6.37 ± 0.59%; p = 0.000). Telomere length was significantly shorter among patients with mitochondrial diabetes and type 2 diabetes than in the control group (1.28 ± 0.54 vs. 1.14 ± 0.43 vs. 1.63 ± 0.61; p = 0.000). However, there was no significant difference between patients with mitochondrial diabetes and those with type 2 diabetes. There was no correlation between telomere length and the peak height G/A ratio. CONCLUSION: Deafness with definite maternal inheritance and normal BMI, associated with elevated blood lactic acid and encephalomyopathy, for the most part, suggest the diagnosis of mitochondrial diabetes . The peak height G/A ratio could reflect the spectrum of age at onset of the disease. Telomere length was shorter in patients with mitochondrial diabetes and those with type 2 diabetes, which suggests that the shorter telomere length is likely involved in the pathogenesis of diabetes but is not specific for this kind of diabetes.

Phosphatase and tension homolog overexpression in insulin resistant diabetic adipose tissue.

OBJECTIVE: To investigate the expression of phosphatase and tension homolog (PTEN) in adipose tissue of KKAy diabetic mice, a mouse model of type 2 diabetes. METHODS: KKAy diabetic mice were fed with high fat diet for 4 weeks. After blood glucose met the criteria of diabetes (over 16.7 mmol/L), mice were randomly divided into 3 groups: a control group (without any treatment), a rosiglitazone group (treated with rosiglitazone 12.5 mg/kg.d once per day), and a metformin group (treated with metformin 3 g/kg.d twice daily). After 4 weeks, we then determined the expression of PTEN and phosphoserine 473-Akt (pS473-Akt) in the epididymal adipose tissue with Western blots. The mice in each group were further divided into the insulin (-) subgroup and insulin (+) subgroup, which were intraperitoneally injected with saline and insulin (5 mU/g body weight), respectively. RESULTS: The expression of PTEN was elevated in the epididymal adipose tissue obtained from KKAy diabetic mice compared with that from the C57BL/6J mice (P<0.001). In accordance with the enhanced expression of PTEN, the level of pS473-Akt stimulated by insulin was decreased in the adipose tissue of KKAy mice compared to the C57BL/6J mice (P<0.001). Treatment with the insulin-sensitizing agents, rosiglitazone and metformin did not inhibit the elevated expression of PTEN in adipose tissue of KKAy diabetic mice. CONCLUSION: PTEN may play an important role in the development of insulin resistance in adipose tissue of type 2 diabetes mice model.

Triceps skinfold thickness trajectories and the risk of all-cause mortality: A prospective cohort study.

BACKGROUND: The measurement of triceps skinfold (TSF) thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution. Despite its clinical utility, the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated. AIM: To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality. METHODS: This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey. Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness. Subjects were classified into subgroups reflective of their respective TSF thickness trajectory. We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality, including contributory factors. RESULTS: Upon adjustment for multiple confounding factors, we discerned that males in the 'Class 2: Thin-stable' and 'Class 3: Thin-moderate' TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the 'Class 1: Extremely thin' subgroup. In the mediation analyses, the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality. For females, a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort. CONCLUSION: In males and non-elderly females, lower TSF thickness trajectories are significantly predictive of heightened mortality risk, independent of single-point TSF thickness, body mass index, and waist circumference.

Dipeptidyl peptidase-4 inhibitors and the risk of infection: A systematic review and meta-analysis of cardiovascular outcome trials.

BACKGROUND: Since adverse events during treatment affect adherence and subsequent glycemic control, understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus (T2DM) therapy. AIM: To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4 (DPP-4) inhibitors. METHODS: Electronic databases were searched. The selection criteria included randomized controlled trials focused on cardiovascular outcomes. In these studies, the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo. Six trials involving 53616 patients were deemed eligible. We calculated aggregate relative risks employing both random-effects and fixed-effects approaches, contingent upon the context. RESULTS: The application of DPP-4 inhibitors showed no significant link to the overall infection risk [0.98 (0.95, 1.02)] or the risk of serious infections [0.96 (0.85, 1.08)], additionally, no significant associations were found with opportunistic infections [0.69 (0.46, 1.04)], site-specific infections [respiratory infection 0.99 (0.96, 1.03), urinary tract infections 1.02 (0.95, 1.10), abdominal and gastrointestinal infections 1.02 (0.83, 1.25), skin structure and soft tissue infections 0.81 (0.60, 1.09), bone infections 0.96 (0.68, 1.36), and bloodstream infections 0.97 (0.80, 1.18)]. CONCLUSION: This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.

Total synthesis of (-)-sessilifoliamide J.

An efficient synthesis of the Stemona alkaloid (-)-sessilifoliamide J (1) in 12 steps and 7.7% overall yield from the known building block 8 is presented. The synthesis features the Corey lactonization reaction and a highly diastereoselective α-methylation reaction to build the spiro-lactone moiety.

[A comparative study of the effects of needle free (INJEX30) versus insulin pen injection on insulin absorption in diabetic patients].

OBJECTIVE: To evaluate the effect of the needle free injection system (INJEX30) and insulin pen on insulin absorption and glycemic control in diabetic patients. METHODS: A total of 30 diabetic patients on insulin therapy without obvious complications were enrolled in the study with average BMI of 25.24 kg/m(2). A comparison study was carried out in those subjects with the INJEX30 and insulin pen at 1(st) day and 5(th) day. After an overnight fasting of 8-10 h, a standard mixed meal (50 g bread, 50 g egg and 250 ml milk) was given to each patient. Blood samples at 0, 20, 40, 60 min of the standard mixed meal were collected to test plasma glucose, serum insulin and C peptide. RESULTS: No difference was shown in fasting plasma glucose, serum insulin and C peptide between the patients with the two injection methods. The area under the curve (AUC) of plasma glucose and serum C peptide was significantly lower after the INJEX30 injection than that after insulin pen injection [plasma glucose AUC (542 ± 172)min·mmol·L(-1) vs (601 ± 199) min·mmol·L(-1), P < 0.01; C peptide AUC (70 ± 53) min·µg· L(-1) vs (80 ± 58) min·µg·L(-1), P < 0.01]. The AUC of serum insulin was significantly higher after the INJEX30 injection than that after insulin pen injection [serum insulin AUC (5621 ± 3790) min·mIU·L(-1) vs (4285 ± 3376) min·mIU· L(-1), P < 0.01]. No difference was found in the AUC of serum insulin between the two injection methods in the patients with BMI below 25.24 kg/m(2), while the AUC of serum insulin was significantly higher after the INJEX30 injection than the insulin pen injection in the patients with BMI above 25.24 kg/m(2) [serum insulin AUC (6453 ± 4099) min·mIU· L(-1) vs (4879 ± 3701) min·mIU·L(-1), P < 0.01]. CONCLUSION: The INJEX30 improves the serum insulin level which may lead to a beneficial effect on the glycemic control. Such effect is more obvious in the overweight patients.

Nursing a patient with latent autoimmune diabetes in adults with insulin-related lipodystrophy, allergy, and exogenous insulin autoimmune syndrome: A case report.

BACKGROUND: Latent autoimmune diabetes in adults (LADA) is a special type of type 1 diabetes mellitus. During the early stages, patients with LADA are treated with oral antidiabetics. However, insulin treatment is still required as islet function gradually declines. Once patients have developed insulin allergy, clinical treatment and nursing care become very challenging. CASE SUMMARY: Here, we report a case of LADA with insulin-related lipodystrophy, allergy, and exogenous insulin autoimmune syndrome during insulin treatment, thus making it very difficult to effectively control glucose levels with insulin. We attempted subcutaneous injection and an insulin pump to desensitize the patient's response to insulin, and finally assisted the doctor to select the appropriate insulin treatment for the patient. We describe the management of this patient from a nursing viewpoint. CONCLUSION: We summarize the nursing experience of a case with complex insulin allergy requiring desensitization treatment. Our approach is very practical and can be applied to similar patients needing insulin desensitization.

[Comprehensive treatment for type 2 diabetes mellitus].

The treatment of type 2 diabetes mellitus (T2DM) is traditionally focused on glycemic control. In recent years, comprehensive treatment approaches including blood sugar control, blood pressure management, and use of antihyperlipidemic agents (e.g. statins) and aspirin play critical roles in improving the outcomes of T2DM. Some newly developed approaches such as stomach reduction surgery also have been applied.

Diabetes insipidus with impaired vision caused by germinoma and perioptic meningeal seeding: A case report.

BACKGROUND: Germinoma is a type of germ cell tumor that most frequently arises in the midline axis of the brain. Impaired vision is a clinical manifestation of germinnoma. Although rare, intracranial germinoma seeding to the perioptic arachnoid space is one cause of visual acuity decrease. CASE SUMMARY: An 11yearold girl who presented with polyuria and polydipsia and subsequently developed diminution of vision. Imaging showed bilateral heterogeneous enhancement of the optic nerve sheaths and atrophy of the optic nerve, and transsphenoidal biopsy revealed a germinoma. The patient experienced poor visual recovery following chemotherapy and radiotherapy. Germinomas are rare and they are mostly identified in children and adolescents. The manifestations include diabetes insipidus, pituitary dysfunction, visual complaints, etc. The mechanisms that lead to visual loss include intracranial hypertension, compression of optic chiasma, and tumor invasion. A literature review was performed to summarize the cases with a tumor infiltrating the optic nerve. Most of the reported patients were adolescents and presented with anterior pituitary hormone deficiency. Enhancement of optic nerve sheaths and optic disc pallor could be identified in most of the cases. The purpose of this report is to provide awareness that in cases where a germinoma is associated with visual loss, though rare, perioptic meningeal seeding should be taken into consideration. CONCLUSION: The case report suggests that children with diabetes insipidus need a complete differential diagnosis.

Liraglutide Inhibits Osteoclastogenesis and Improves Bone Loss by Downregulating Trem2 in Female Type 1 Diabetic Mice: Findings From Transcriptomics.

Background: The mechanisms of bone fragility in type 1 diabetes (T1D) are not fully understood. Whether glucagon-like peptide-1 receptor (GLP-1R) agonists could improve bone quality in T1D context also remains elusive. Aims: We aimed to explore the possible mechanisms of bone loss in T1D and clarify whether liraglutide has effects on bone quality of T1D mice using transcriptomics. Methods: Female streptozotocin-induced diabetic C57BL/6J mice were randomly divided into four groups and received the following treatments daily for 8 weeks: saline as controls, insulin, liraglutide, and liraglutide combined with insulin. These groups were also compared with non-STZ-treated normal glucose tolerance (NGT) group. Trunk blood and bone tissues were collected for analysis. Three tibia from each of the NGT, saline-treated, and liraglutide-treated groups were randomly selected for transcriptomics. Results: Compared with NGT mice, saline-treated T1D mice manifested markedly hyperglycemia and weight loss, and micro-CT revealed significantly lower bone mineral density (BMD) and deficient microarchitectures in tibias. Eight weeks of treatment with liraglutide alone or combined with insulin rescued the decreased BMD and partly corrected the compromised trabecular microarchitectures. Transcriptomics analysis showed there were 789 differentially expressed genes mainly mapped to osteoclastogenesis and inflammation pathways. The RT-qPCR verified that the gene expression of Trem2, Nfatc1, Trap, and Ctsk were significantly increased in the tibia of T1D compared with those in the NGT group. Liraglutide treatment alone or combined with insulin could effectively suppress osteoclastogenesis by downregulating the gene expression of Trem2, Nfatc1, Ctsk, and Trap. Conclusions: Taken together, increased osteoclastogenesis with upregulated expression of Trem2 played an important role in bone loss of T1D mice. Liraglutide provided protective effects on bone loss in T1D mice by suppressing osteoclastogenesis.

[Role of gastric surgery in treating obese patients with type 2 diabetes].

Gastric surgery can reduce the body weight in obese patients with type 2 diabetes and decrease their blood glucose. In the latter, incretins may play certain roles.

TNFα Mediates the Interaction of Telomeres and Mitochondria Induced by Hyperglycemia: A Rural Community-Based Cross-Sectional Study.

This study is aimed at evaluating the relationship between leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) in a noninterventional rural community of China with different glucose tolerance statuses. In addition, we investigate whether the indicators of oxidative stress and inflammation were involved and identify mediators among them. A total of 450 subjects in rural China were included and divided into two groups according to a 75 g oral glucose tolerance test (OGTT): the abnormal glucose metabolism (AGM, n = 257, 57.1%) group and the normal glucose tolerance (NGT, n = 193, 42.9%) group. Indicators of oxidative stress (superoxide dismutase (SOD) and glutathione reductase (GR)) and inflammatory indices (tumor necrosis factor α (TNFα) and interleukin-6 (IL-6)) were all determined by ELISA. LTL and mtDNAcn were measured using a real-time PCR assay. Linear regressions were used to adjust for covariates that might affect the relationship between LTL and mtDNAcn. Mediation analyses were utilized to evaluate the mediators. In the AGM, LTL was correlated with mtDNAcn (r = 0.214, p = 0.001), but no correlation was found in the NGT. The association between LTL and mtDNAcn was weakened after adjusting for inflammatory factors in the AGM (p = 0.087). LTL and mtDNAcn were both inversely related to HbA1c, IL-6, TNFα, and SOD activity. Mediation analysis demonstrated that TNFα was a significant mediator in the telomere-mitochondrial interactome in the AGM. This result suggests that inflammation and oxidative stress may play a vital role in telomere shortening as well as mitochondrial dysfunction. In the subjects with hyperglycemia, a significant positive correlation is observed between LTL and mtDNAcn, which is probably mediated by TNFα. TNFα may be considered a potential therapeutic target against aging-related disease in hyperglycemia.

Recent progress in Keap1-Nrf2 protein-protein interaction inhibitors.

Therapeutic targeting the protein-protein interaction (PPI) of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its main regulator, Kelch-like ECH-Associating protein 1 (Keap1) has been emerged as a feasible way to combat oxidative stress related diseases, due to the key role of Nrf2 in oxidative stress regulation. In recent years, many efforts have been made to develop potent Keap1-Nrf2 inhibitors with new chemical structures. Various molecules with diverse chemical structures have been reported and some compounds exhibit high potency. This review summarizes peptide and small molecule Keap1-Nrf2 inhibitors reported recently. We also highlight the pharmacological effects and discuss the possible therapeutic application of Keap1-Nrf2 inhibitors.

Heteroplasmy level of the mitochondrial tRNaLeu(UUR) A3243G mutation in a Chinese family is positively associated with earlier age-of-onset and increasing severity of diabetes.

OBJECTIVE: To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. METHODS: Genomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations. RESULTS: Family members on the maternal side all harbored the tRNALeu(UUR) A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980 (P = 0.02). Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found. CONCLUSIONS: The main cause of diabetes in this pedigree is the tRNALeu(UUR) A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNALeu(UUR) A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.

[Gefitinib improves insulin sensitivity in Wistar diabetes rats models].

OBJECTIVE: To investigate the effect of Gefitinib on insulin sensitivity in rats of type-2 diabetes and its mechanism. METHODS: Normal Wistar rats were fed with high sucrose-fat diet for 1 month and then injected intraperitoneally with streptozotocin (STZ). The rats satisfying the definity of type-2 diabetes were divided into 3 groups and given control solution (0.9%NaCl), low-dose Gefitinib and high-dose Gefitinib for 8 days, respectively. Body weights, FBG and FINS were recorded before, just after and 7 days after administration, respectively. After the second round of administration executed the rats and got the livers from rats. Compared the expression of insulin receptor substrate-1 (IRS-1) and phosphatidylinositol-3-kinase (PI3K) genes in liver among the 3 groups with semi-quantitative Reverse Transcription-Polymerase Chain Reaction (PCR). RESULTS: Normal Wistar rats fed with high sucrose-fat diet for 1 month and then injected intraperitoneally with STZ could establish type-2 diabetes model. After administration, insulin sensitivity index (ISI) of Gefitinib groups were significantly increased compared with control group (2.96 +/- 1.38 vs 0.92 +/- 0.20, P < 0.05). There Were no significant difference between the two dose groups (2.95 +/- 1.51 vs 2.96 +/- 1.38, P > 0.05). 7 days after administration, the improved ISI did not change (2.03 +/- 0.72 vs 2.99 +/- 0.63, P > 0.05). Body weights of the 3 groups had no significant difference. The expression of IRS-1 gene significantly decreased in Gefitinib groups compared with control group [(3.3 +/- 1.5)% vs (6.3 +/- 2.4)% P < 0.05] and with no obvious difference between the two dose groups [(3.3 +/- 1.5)% vs (3.2 +/- 1.8)%, P > 0.05], while the expression of PI3K gene significantly increased in Gefitinib groups compared with control group [(1.27 +/- 0.73)% vs (0.41 +/- 0.24)%, P < 0.05] also with no obvious difference between the two dose groups [(1.27 +/- 0.73)% vs (1.43 +/- 0.71)%, P > 0.05]. CONCLUSIONS: Gefitinib can improve insulin sensitivity in rats of type-2 diabetes. 2 t(1/2) after administration, the effect still existed. The effect probably due to the increase of PI3K/Akt pathway of insulin signaling, and had no relationship with body weight in our study dose range.