Volume 85  ·   Issue 35  ·  2005

With the rapid development of China's economy and the improvement of people's material life, the prevalence of diabetes mellitus has increased by about 3~6 times in the past 20 years. The epidemiological investigation of diabetes mellitus carried out in the past 5 years shows that the standardized prevalence of diabetes mellitus among people over 18 years old in China is 3.4%, and the prevalence of diabetes mellitus is as high as 9.78% in Shanghai. The chronic complications of diabetes mellitus are also very serious. The retrospective analysis of the vascular complications of diabetes mellitus among inpatients in endocrinology departments of tertiary hospitals in various provinces and cities in China from 1991 to 2000 showed that 24.3%, 33.6% and 60.3% of diabetic patients had retinopathy, nephropathy and neuropathy, respectively. In addition, 14.9% of diabetic patients had coronary heart disease. The chronic complications caused by diabetes mellitus seriously affect the quality of life and also lead to the rapid increase of medical expenses. Compared with uncomplicated diabetic patients, the medical expenses of patients with complications have increased by 3~4 times. According to the prediction of WHO experts, diabetes mellitus will be widely prevalent all over the world in the next 20 years, And mainly in Asia. China is a country with a large population in the world, which may become one of the countries with the highest number of diabetic patients. Therefore, it will be a long-term and arduous task for medical workers to effectively prevent and treat the occurrence and development of diabetes and its complications. Diabetes has the characteristics of complex etiology, hidden onset, and difficulty in controlling blood sugar standard. Aiming at these characteristics, clinical thinking and practice will be beneficial to improve the effect of diabetes prevention and treatment.

The prevalence of diabetes mellitus and metabolic syndrome is increasing rapidly worldwide, which is largely due to the rising prevalence of obesity caused by overnutrition and leisure lifestyle. The occurrence of type 2 diabetes mellitus and metabolic syndrome and related diseases in China is also on the rise; The prevalence rate of overweight, obesity, impaired glucose regulation reached 29.5%, 4.3%, 10.8, 9.8% of type 2 diabetes and 17.14% of metabolic syndrome among urban adults over 20 years old in China. In recent years, people have gained new understanding of the study of diabetic complications from the perspective of vascular disease mechanism, especially the exploration of the pathogenesis of type 2 diabetes itself has also produced new ideas.

Insulin resistance (IR) is a hot research topic in recent years, so it is often required to quantitatively detect IR or insulin sensitivity index (ISI, that is, the reciprocal of IR). There are many methods to detect IR, so I will briefly review it [1]. IR refers to the reduction of the biological effects of a certain amount of insulin. The biological effects of insulin have many aspects, such as the clearance of glucose (G) in the periphery, the inhibition of liver glucose export or the action of lipase sensitive to hormone, etc. Different tissues have different sensitivities to the action of insulin. 　　

In the past 20 years or so, the fastest progress in the research of diabetes etiology has been the discovery of a series of single gene mutation diabetes.In 1999, WHO classified these single gene mutation diabetes,such as diabetes caused by endocrinopathies,pancreatic exocrinopathies,drugs and infections and hereditary syndromes that may be related to diabetes,as special type diabetes.In the past, a considerable part of type 2 diabetes, which was considered as polygenic diseases, was proved to be caused by genetic heterogeneity, i.e., controlled by a single major gene.With the deepening of research on special type diabetes,it will provide new ways for preventing, delaying pancreatic islet β cell failure and reducing insulin resistance.

Objective to investigate the manifestations of diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) in brain MS, and to analyze their value in estimating the pathological changes of brain MS. Methods 41 cases of brain MS and 11 cases of subacute cerebral infarction were performed combined imaging with DWI and DTI. The signal characteristics of MS lesions and infarct lesions on DWI and ADC, EADC and FA maps obtained by DTI were analyzed. The ADC, EADC and FA values of the core, periphery and periphery of acute MS lesions, chronic MS lesions and infarct lesions were quantitatively analyzed, and the pathological differences of various lesions or sites were estimated. Results the DWI of chronic and small MS lesions showed isosignal. The acute and chronic larger MS lesions and infarct lesions showed different degrees of high signal on DWI images. The EADC diagram showed that 13 high signal lesions were distributed outside the periphery of acute MS lesions, and the rest of the lesions showed low signal. The ADC value of cerebral infarct lesions was similar to that of chronic MS lesions (P>0.05), with the highest increase. The two were>the core of acute MS lesions (P<0.05)>MS acute perilesional (P<0.05); EADC value MS peri-acute lesion>MS acute lesion core (P<0.05)>Chronic MS lesions and infarcts (P<0.05); The FA value of cerebral infarction lesions was the lowest, followed by chronic MS lesions, the former was lower than the latter (P<0.05). The core of MS acute lesion was lower than that around MS acute lesion (P<0.05), which were lower than those of infarction and chronic MS (P<0.05). The lesions with the lowest ADC value and the highest EADC value were shown outside the acute lesions of MS. Conclusion The judgment of the high signal significance of DWI should be combined with the medical history and routine MRI findings. EADC diagram is more accurate than DWI to judge the limitation of water molecule diffusion in the lesion. The increase of ADC value accompanied by the decrease of FA value reflects the degree of tissue structure destruction in the lesion to some extent.

Objective to evaluate the application value of bladder tumor antigen (BTAstat), nuclear matrix protein 22 (NMP22), hyaluronic acid (HA), survivin, CD44v6, vascular endothelial growth factor (VEGF) and VUC in the diagnosis of bladder tumors.Methods The indexes of 52 patients with bladder tumor, 11 patients with benign urinary tract diseases and 10 normal subjects were detected in clean morning urine. The sensitivity, specificity, coefficient of variation, detection time and cost of each index and the combination of two indexes were calculated, and their application value was evaluated. Results There were significant differences between the tumor group and the control group. The sensitivity and specificity were: VUC (42.3%, 100%), respectively; BTAstat (78.8%, 90.5%); NMP22 (76.9%, 81.0%); HA (86.5%, 90.5%); Survival protein (67.3%, 85.7%); CD44v6 (50.0%, 85.7%); VEGF (69.2%, 95.2%). The highest sensitivity of combined indexes was NMP22+ HA and HA + CD44v6 (96.2%), the lowest was VUC + CD44v6 (67.3%), the highest specificity was VUC + NMP22 and VUC + VEGF (95.2%), and the lowest was HA + survival protein (66.7%). BTAstat is the easiest operation and the lowest cost of HA detection. BTAstat and VUC have the highest reproducibility. Conclusion All indexes have application value in the diagnosis of bladder tumors. Except CD44v6, the diagnostic sensitivity of all indexes increases with the increase of staging and grading.

Objective to construct a siRNA-expressing plasmid vector pSilencer3.1-H1hygro with hepatitis B virus (HBV) S gene as the target site, and to observe the effect of siRNA on HBV in vitro.Methods HepG2.2.15 cells were used as the target cells, and the siRNA-expressing plasmid vector pSilencer3.1-H1hygro was transfected with liposome Metafectene in the cells. The HBsAg and HBeAg in the cell supernatant were detected by time-resolved immunofluorescence assay (IFMA assay), the supernatant DNA was detected by quantitative polymerase chain reaction (FQ-PCR), and the mRNA of HBV was detected by reverse transcription (RT) -PCR. Results A transcription plasmid vector expressing siRNA was successfully constructed, and siRNA could inhibit the antigen expression and virus replication of HBV. The inhibition rates of 1, 2 and 4 μ g siRNA on HBsAg were 75%, 82% and 89%, respectively. The inhibition rates of HBeAg were 32%, 38% and 43%, respectively; The inhibition rate of HBV DNA was 30%, 43% and 49%, respectively; The inhibition rate of HBV RNA was 30%, 70% and 90%, respectively. Conclusion the siRNA targeting HBV S region can inhibit the expression and replication of HBV antigen; siRNA inhibition was dose-dependent and sequence-specific.

Objective to investigate the effect and mechanism of recombinant interleukin-11 (rhIL-11) combined with recombinant granulocyte colony stimulating factor (rhG-CSF) on graft versus host disease (GVHD) after allogeneic bone marrow transplantation in mice. Methods A model of acute GVHD after allogeneic bone marrow transplantation was established. C57BL/6H-2b was used as donor mice, rhIL-11, rhG-CSF or their combination were used as mobilizers, and BALB/CH-2d mice were randomly divided into 5 groups after lethal dose (8.0 Gy) irradiation. Group A was irradiated alone (10 mice), Group B was GVHD control group (18 mice), Group C was G-CSF transplantation group (18 mice), Group D was IL-11 transplantation group (18 mice), and Group E was combined transplantation group (18 mice). Bone marrow cells and spleen cells of donor mice were transplanted 4 h after irradiation. The survival and mortality of mice after transplantation were observed. Chimera formation was determined by flow cytometry, and mixed lymphocyte reaction was detected by tetramethylazo salt (MTT) assay The difference was statistically significant (P<The 30-day survival rates were 0, 27.3% (3/11), 36.4% (4/11) and 63.6% (7/11) in groups B, C, D and E, respectively. The pathological changes of GVHD were observed in mice in group B, and the degree of GVHD was closely related to the time of occurrence of GVHD. Three mice in Group E developed GVHD within 20 days after transplantation, and the pathological changes were milder than those in other groups. Compared with those in Group B, C and D, the levels of IFN-γ in splenocyte culture supernatant in Group E were lower at 14 days after transplantation (92 pg/ml ± 14 pg/ml vs 172 pg/ml ± 31 pg/ml, 132 pg/ml ± 23 pg/ml, 117 pg/ml ± 28 pg/ml, all P<0.01), the levels of IL-4 were higher (36 pg/ml ± 7 pg/ml vs 16 pg/ml ± 4 pg/ml, 26 pg/ml ± 4 pg/ml, 24 pg/ml ± 4 pg/ml, all P<The levels of tumor necrosis factor α (TNF-α) in groups D and E were similar, but significantly lower than those in groups B and C (both P<0.01), and the lymphocyte proliferation of host antigen in group E was lower than that in group B, C and D (0.22±0.08 vs 0.87±0.14, 0.54±0.21, 0.49±0.18, all P<Conclusion rhIL-11 combined with rhG-CSF can produce synergistic effects and alleviate GVHD in donors, which may be related to the polarization of T cells to Th2 cytokines and the decrease of inflammatory mediators such as TNF-α in recipients.

Objective to investigate the relationship between microsomal triglyceride transfer protein gene polymorphism (MTP-493G/T) and blood lipid levels in black-clothed Zhuang population in Guangxi. Methods Blood pressure, height, weight, body mass index, blood lipid and apolipoprotein were measured by cluster sampling method in 500 black-clothed Zhuang population aged 7-83 years. Detection of MTP-493G/T allele and its genotype distribution frequency by polymerase chain reaction combined with allele-specific oligonucleotide probe point hybridization; Results (1) The frequencies of G and T alleles of MTP-493 were 0.74 and 0.26, respectively, and the frequencies of GG, GT and TT genotypes were 0.58 (289/500), 0.33 (166/500) and 0.09 (45/500), respectively; The frequencies of G and T alleles were 0.73 and 0.27, respectively, and the frequencies of GG, GT and TT genotypes were 0.56 (281/500), 0.34 (172/500) and 0.09 (47/500), respectively. (2) The levels of total cholesterol, triglyceride, low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B in individuals with TT genotypes were significantly higher than those with GG and GT genotypes (P<0.05 or P<Conclusion MTP-493 G/T single base mutation exists in the black-clothed Zhuang population in Guangxi, but the G and T alleles and the distribution frequencies of GG, GT and TT genotypes are not statistically significant compared with those in the Han population. TT genotype individuals are associated with increased levels of total cholesterol, triglyceride, LDL-C and apolipoprotein B.

Objective to investigate the occurrence and clinical characteristics of transitional cell carcinoma (TCC) in uremic maintenance dialysis patients who had taken traditional Chinese medicine containing aristolochic acid (AA). Methods 283 maintenance dialysis patients who were treated in the dialysis center of Peking University First Hospital from April 2004 to July 2004 were investigated and screened. The incidence of TCC and clinicopathological characteristics of TCC were investigated, and the relationship between the medication characteristics, dialysis-related factors and residual urine volume and TCC was further analyzed. Results Among 283 maintenance dialysis patients, 118 were males and 165 were females, aged 22-88 years (mean 59 ± 13 years). A total of 24 patients had TCC, the incidence rate was 8.48%, of which 66 had taken aristolochic acid-containing drugs. The incidence rate of TCC was significantly higher (22/66 cases, 33.3%) than that of those who had not taken drugs (2/198 cases, 1.0%, P<0.001). Among the 18 patients with TCC related to aristolochic acid drugs, the main drugs were Longdan Xiegan Pill (15 cases) and Guanxin Suhe Pill (3 cases), 94.4% of them were long-term conventional doses, and the average time from the start of medication to the onset of TCC was 10 years. Compared with the patients without TCC, there was no obvious difference in the characteristics of medication and dialysis mode between the two patients, and TCC was only seen in patients with residual urine volume>100ml. The first manifestation of TCC patients was intermittent painless macroscopic hematuria, and the positive detection rate of urinary nuclear matrix protein 22 could reach more than 90% by imaging methods. The proportion of TCC in the upper urinary tract was higher in 18 patients (11/18, 61.11%), and the recurrence rate after routine surgical treatment was 27.8%. Conclusion The incidence of urinary transitional cell carcinoma in uremic dialysis patients with aristolochic acid is high, and the monitoring of these patients should be strengthened to facilitate the early detection and treatment of the disease.

Objective to observe the effect of co-encapsulation of rat hepatocytes, transgenic hepatic stellate cell line HGF/CFSC and/or rat bone marrow-derived Thy-1+ β 2M-cells (BDTC) on the biological activity of hepatocytes, and to observe the effect of mixed cell microcapsules transplanted into peritoneal cavity on the improvement of liver function in rats with acute liver failure. Methods Microcapsules containing hepatocytes or mixed cells were prepared by microcapsule generator. According to the types of cells encapsulated in the microcapsules, they were divided into microencapsulated hepatocytes group, microencapsulated hepatocytes + CFSC/HGF group) and microencapsulated hepatocytes + CFSC/HGF + BDTC group. The rats with acute liver failure caused by 90% subtotal hepatectomy were divided into empty capsule control group and the above three experimental groups (10 rats in each group) according to different types of microcapsule transplantation. The general condition, survival time, blood biochemical changes, liver tissue regeneration and histological characteristics of microencapsulated graft were observed at different times after peritoneal implantation. Results Compared with the hepatocyte microencapsulation alone, the hepatocyte survival time in mixed cell microencapsulation was more than 1 times, and the albumin secretion and urea synthesis in culture medium were significantly increased (all P<0.01); Compared with the control group, after microencapsulated hepatocytes or microencapsulated mixed hepatocytes transplantation, the liver function and survival rate of acute liver failure rats were significantly improved (10/10 vs 1/10), and the liver tissue regeneration was complete; After 21~42 days of transplantation, some microcapsules were attached to the liver surface and vascularized. There were different degrees of fibrosis on the surface of the microcapsules, but there were still viable cells in the microcapsules. The microencapsulated mixed hepatocyte group was better than the microencapsulated hepatocyte group.Conclusion Co-microencapsulation of mixed cells can significantly improve the survival life, morphology and function of intracapsular hepatocytes, and microencapsulated mixed hepatocyte transplantation into peritoneal cavity can significantly promote the recovery of liver function in rats with acute liver failure.

First, the policy environment is not satisfactory, which is mainly manifested in two aspects: on the one hand, within the scope of existing policies, the threshold for social capital to enter the market is too high, which generally requires strict approval from all levels and levels, the procedures are complicated, and the admission qualification standard is very high. At present, the Chinese government has relaxed the admission conditions to a certain extent. In May 2002, the Ministry of Health and the former Ministry of Foreign Trade and Economic Cooperation issued a<The Interim Measures for the Administration of Sino-foreign Joint Ventures and Cooperative Medical Institutions "once again lowers the threshold for foreign capital to enter China's medical industry, that is, the total investment is not less than 20 million yuan, and the maximum shareholding ratio can reach 70%. 　　

Objective to explore and find a simple and clinically feasible method to evaluate the function of pancreatic islet β cells. Methods From November 2001 to August 2002, 214 inpatients and outpatients and employees of our hospital were divided into 4 groups according to the criteria of World Health Organization (WHO) in 1999, including 39 cases in normal glucose tolerance (NGT) group, 29 cases in impaired glucose tolerance (IGT) group, 43 cases in newly diagnosed type 2 diabetes mellitus (NT2DM) group and 103 cases in originally diagnosed type 2 diabetes mellitus (PT2DM) group. The changes of blood glucose, true insulin (TI) and proinsulin (PI) levels after fasting and 2, 4 and 6 min after arginine stimulation were measured respectively. Results (1) The fasting PI/TI and PI/ (TI + PI) were significantly lower in NGT group (19.09%±2.02% and 15.31%±1.14%) than in IGT group (38.83%±6.80% and 24.43% ±2.43%, all P<0.05). (2) The secretion curves of TI/blood glucose after arginine stimulation were IGT, NGT, NT2DM, PI and PI/blood glucose in IGT, NT2DM and PT2DM groups all reached peak values at 2 min. (3) The changes of PI/TI in each group were mirror image phenomenon with the changes of TI/blood glucose mentioned above, and reached trough values at 2 min (NGT 2.99%±0.27%, IGT 6.70%±1.38%, NT2DM 10.52%±1.46%, PT2DM 11.12%±1.51%). The changes and differences of PI/ (TI + PI) were similar to those of PI/TI, and the 2 min trough values of these two parameters were ranged from small to large as NGT, IGT, NT2DM and PT2DM. Conclusion PI/TI and PI/ (TI + PI) values at 2 min after arginine stimulation can be used as a simple and practical index for clinical evaluation of β cell function.

Objective to compare the effects of quick-acting insulin analogue insulin aspart and neutral soluble human insulin on intensive insulin pump therapy in newly diagnosed type 2 diabetic patients. Methods 59 newly diagnosed type 2 diabetic patients, 35 males and 24 females, aged 51 ± 12 years, with body mass index 25 kg/m2 ± 3 kg/m2, were randomly treated with quick-acting insulin analogue insulin aspart (analogue group, 30 cases) and neutral soluble human insulin (human insulin group, 29 cases) for 2 weeks of insulin pump therapy. Results on the second day of insulin pump treatment, the blood glucose of the analog group was significantly lower than that of the human insulin group (8.4 mmol/L ± 2.8 mmol/L vs 11.3 mmol/L ± 3.8 mmol/L, 9.0 mmol/L ± 2.4 mmol/L vs 10.7 mmol/L ± 2.8 mmol/L, P<0.05), and the degree of blood glucose decrease in the analogue group was also significantly greater than that in the human insulin group (4.6 mmol/L ± 0.8 mmol/L vs 5.3 mmol/L ± 0.9 mmol/L, 7.3 mmol/L ± 2.2 mmol/L vs 8.1 mmol/L ± 1.8 mmol/L, P<0.05). On the 14th day of treatment, only fasting blood glucose was different; After stopping the treatment, the difference of fasting blood glucose and 2 hours after breakfast and dinner was statistically significant between the two groups. The ideal blood glucose control time in the analog group was shorter than that in the human insulin group (2.0 d vs 6.0 d, P<The functional indexes of islet β cells, such as the acute insulin secretion phase in intravenous glucose tolerance test, the area under the curve of insulin and C-peptide, Homa β and proinsulin, were not significantly different between the two groups. Only mild hypoglycemic events were observed in the two groups during treatment: 8 cases (27%) in analog group and 10 cases (35%) in human insulin group. Conclusion Compared with human insulin, the rapid-acting insulin analog insulin aspart can improve fasting and postprandial blood glucose faster and better in newly diagnosed type 2 diabetes mellitus.

Objective to study the mutation of WFS1 gene in a Chinese family of patients with Wolfram syndrome. Methods the mutation of 8 exons and flanking introns of WFS1 gene in a patient with Wolfram syndrome and family members were screened by PCR-DNA direct sequencing. The structure and function of the mutant protein were estimated by bioinformatics methods.The results showed that there was a deletion mutation in codon 417 of exon 8, namely F417del. The proband was a mutant homozygous, whose parents were intimate cousins, both of which were mutant heterozygous.The mutation of F417del was located in the transmembrane region and lost a non-polar amino acid.Bioinformatics analysis suggested that the mutation could change the secondary structure of the transmembrane region and decrease the hydrophobicity of the mutant protein.Conclusion The F417del mutation found in this study is a new mutation of Wolfram syndrome that has not been reported yet.

Objective to investigate the role of NeuroD1/BETA2 gene in the pathogenesis of familial type 2 diabetes mellitus in northern China. Methods PCR and single-strand conformation polymorphism (PCR-SSCP) were used to screen the mutation of the coding region of NeuroD1/BETA2 gene in 188 probands of type 2 diabetes mellitus. The mutation was confirmed by DNA sequence analysis, and 130 normal subjects were genotyped. The differences of alleles, genotype frequency and clinical phenotype between the two groups were compared. Results Polymorphism A45T and mutation Gly12Arg were found in the screening of NeuroD1/BETA2 gene. The frequency of A45T in patients and normal subjects was 19.7% and 10%, respectively, with statistically significant differences (P<Conclusion NeuroD1/BETA2 gene polymorphism A45T is associated with familial type 2 diabetes in Chinese population. NeuroD1/BETA2 gene or nearby genes play a certain role in the pathogenesis of familial type 2 diabetes in Chinese population, and Gly12Arg may be the mutation leading to diabetes.

The patient was a 45-year-old female who developed shortness of breath and left hypochondrial pain without obvious trigger 2 months ago. She was admitted to hospital because of pericardial effusion on chest radiograph. Past history: 4 years ago, she underwent liposarcoma resection of the lateral left thigh and postoperative radiotherapy. She had suffered from tuberculosis and was cured. Physical examination: general condition was acceptable, and the superficial lymph nodes of the whole body were not palpable and swollen. The breathing sounds of both lungs were clear, the breathing sounds of the left lung were slightly low, without dry and wet rales, and the heart boundary was knocked into a flask. The heart rate was 95 beats/min, the rhythm was uniform, the heart sounds were distant, no pathological murmur was heard in each valve area, the abdomen was flat and soft, there was tenderness under the xiphoid process, and no mass was palpable.

A 13-year-old child was admitted to the hospital on February 17, 2005 due to unexplained high fever for more than 1 month. A month ago, he had sudden fever of 38~39℃ without trigger, like a cold, cough and cough a small amount of white phlegm. There were no symptoms such as chest tightness, chest pain, night sweats and joint pain. After being given intravenous infusion of penicillin in the local hospital, it was transferred to a superior hospital and then given intravenous infusion of antibiotics such as azithromycin for 2 weeks, but it was not effective. The body temperature rose to 39.5~40℃, anorexia, nausea, vomiting stomach contents, non-jetting, paroxysmal chills and mild headache. 　　

There is a hypothesis that multiple antigen vaccines, such as measles-mumps-rubella vaccine, or concentrated vaccination of multiple vaccines can cause immune dysfunction and "overload" of the immune system, resulting in immune infection outside vaccine.Anders Hviid et al. studied the vaccination and infection situation of more than 800,000 children in 11 years, and put forward a dissension to this hypothesis. The results of their research were published in the journal JAMA on Aug. 10 (Anders Hviid et al., JAMA. 2005; 294:699-705).

In July 2005, the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, performed autologous hematopoietic stem cell transplantation (AHSCT) in a patient with autoimmune hemolytic anemia (AIHA). This is the first time in China that AHSCT combined with anti-CD20 monoclonal antibodies (Rituximab, Rituximab) was used to treat AIHA. The patient has recovered and been discharged.

Health promotion has played an important role in guiding global, national and community public health policies and in reducing health hazards at the global and community levels. The Sixth Global Health Promotion Conference, jointly hosted by the World Health Organization and the Ministry of Health of Thailand, was held in Bangkok from 7 to 11 August 2005. The Conference adopted a measure to promote human health<Bangkok Charter>.

In order to strengthen the routine surveillance of infectious diseases in China and provide scientific basis for formulating strategies for prevention and control of infectious diseases, the Ministry of Health has organized and formulated 13 national surveillance programs for key infectious diseases (for trial implementation). The specific contents of each program will be published on the website of the Ministry of Health one after another. At present, the following 7 programs have been issued, and the surveillance programs for cholera, plague and rabies will be issued in the future.

Glucose transmembrane transport mediated by glucose transporter 4 (GluT4) is a rate-limiting step for adipose and muscle tissues to utilize glucose. Glucose tolerance and insulin sensitivity were enhanced in mice with adipose tissue-specific overexpression of GluT4 (GluT4- / -), and insulin sensitivity was enhanced even after diabetes was caused by destruction of pancreatic islet β cells in mice. In mice with GluT4- / - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - A new adipokine involved in the development of insulin resistance, retinol-binding protein 4 (RBP4), was identified. The results were published on July 21, 2005<Nature, 2005, 436:356-362.