Volume 03 · Issue 02 · 2011

Because of the increasingly prominent health problems related to obesity in the world, adipocyte biology has become a key issue in the prevention and treatment of many diseases. The development of technologies such as gene chips, protein chips, and gene manipulation has accelerated the understanding of the genes, proteins, and pathways required for adipocyte regulation. However, there are a variety of adipocyte research models, which are different in proliferation and differentiation, and the bias of model selection often limits the application value of these experimental techniques. This paper will explore the similarities and differences of commonly used adipocyte research models, in order to provide a basis for model selection and correct interpretation of experimental data in the experimental design stage, and promote the biological research of adipocyte.

Obesity is one of the major public health problems facing the world at present. Obesity is not only a major risk factor for various cardiovascular diseases and metabolic diseases, but also an important pathogenic factor. However, in recent years, some cross-sectional analyses and retrospective studies have found that BMI is negatively correlated with cardiovascular prognosis and target organ damage. Some scholars call this phenomenon "obesity contradiction". The occurrence of obesity contradiction may be related to fat phenotype, and the age of patients, metabolic reserve and some confounding factors also have some influence. At present, the research on the contradiction of obesity mostly uses body mass index as the index to judge obesity; However, BMI cannot truly reflect the content and distribution of adipose tissue^[1]。 Therefore, how to evaluate the contradictory phenomenon of obesity objectively still needs to be discussed in depth.

To investigate the effect of exercise training on the expression of peroxisome proliferator-activated receptor (PPAR)-δ in muscle and adipose tissue in high fat diet induced obese rats and to explore the possible mechanism of improving insulin resistance.

Sixty male nine-week old Wistar rats with a weight of 135 to 150 g were randomly selected by using random number table for production of obese rats models with high fat diet for 6 weeks, another 20 rats were fed with ordinary feed as control. A total of 54 rat models were established successfully and were divided randomly into three groups: high-fat diet group (HFD), high fat diet whilst exercise group (E-HFD), exercise after high fat diet group (HFD-E), 18 rats in each group; and 16 rats with ordinary diet were set as control: the normal diet group (RD). The rats in all groups were given exercise training for 6 weeks according to the methods from literature. After the exercise training was done, the body weight, levels of tumor necrosis factor(TNF)-α, leptin, interleukin(IL)-1, fasting glucose, fasting insulin, insulin sensitivity index (ISI) and expression of PPAR-δ, GLUT-4, PI3K mRNA and PPAR-δ protein in muscle and adipose tissue in the groups were investigated and compared. Two-sidet test was used in the comparison of data between the groups.

The ISI in group HFD, E-HFD and HFD-E was 1.13±0.21, 2.09±0.32 and 1.80±0.34, respectively; and it increased for 71.1% and 45.7% in group E-HFD and HFD-E compared to that in group HFD (all P<0.05). Compared with that in group HFD, the TNF-α level in group E-HFD and HFD-E decreased for 20.0% and 9.2% respectively ((101±24)ng/L, (81±16) ng/L and (92±19) ng/L, respectively)(allP<0.05). Compared to those in group HFD, the level of leptin and IL-1 in group E-HFD and HFD-E decreased significantly(allP<0.05). The expression level of PPAR-δ, GLUT-4, PI3K mRNA in muscle and fat tissue in group E-HFD and HFD-E increased significantly compared with those in group HFD, especially in group E-HFD(allP<0.05). Compared with that in group HFD, the expression of PPAR-δ in muscle and fat tissues in group E-HFD increased for 388.4% and 203.2%, respectively(allP<0.05); and the expression of PPAR-δ in muscle and fat tissues in group E-HFD increased for 272.9% and 117.9%, respectively(allP<0.05).

Exercise training improves insulin resistance and decreases the level of serum leptin, TNF-α and IL-1 in high fat diet induced obese rat, and this effect is probably mediated by up-regulation of PPAR-δ.

To investigate the effect of obestatin (OB) on lipotoxicity-induced apoptosis in pancreatic β-cell line INS-1.

The INS-1 cells were divided into the following groups: 5% bovine serum albumin (BSA) group, 5% BSA+ 1 nmol/L OB group, 5% BSA+ 10 nmol/L OB group, 5% BSA+ 100 nmol/L OB group, 5% BSA+ 500 nmol/L OB group, 0.5 mmol/L palmitic acid (PA) group, 0.5 mmol/L PA+ 1 nmol/L OB group, 0.5 mmol/L PA+ 10 nmol/L OB group, 0.5 mmol/L PA+ 100 nmol/L OB group, 0.5 mmol/L PA+ 500 nmol/L OB group. Cell survival rate was evaluated by using CCK-8. To investigate cell apoptosis, the INS-1 cells were then divided into 7 groups, including 5% BSA group, 100 nmol/L OB group, 50 μmol/L LY294002 group, 0.5 mmol/L PA group, 0.5 mmol/L PA+ 50 μmol/L LY294002 group, 0.5 mmol/L PA+ 100 nmol/L OB group, and 0.5 mmol/L PA+ 100 nmol/L OB+ 50 μmol/L LY294002 group. The INS-1 cells were finally divided into 5% BSA group, 0.5 mmol/L PA+ 100 nmol/L OB 0 min group, 0.5 mmol/L PA+ 100 nmol/L OB 15 min group, 0.5 mmol/L PA+ 100 nmol/L OB 30 min group, and 0.5 mmol/L PA+ 100 nmol/L OB 60 min group to assess total PKB and p-PKB (Ser 473) levels. Data were analyzed by using One-way ANOVA.

OB alone dose-dependently promoted cell growth, and 100 nmol/L OB produced best result when compared with 5% BSA alone. Cell viability was decreased by 35% after PA treatment. Treatment with OB dose-dependently prevented PA-induced toxicity, most effectively by 35% at 100 nmol/L, with 10 nmol/L being the lowest active concentration by 23% when compared with PA alone. The percentage of apoptosis reached to 26% after PA treatment for 24 h, which was significantly increased when compared with BSA alone. Treatment with OB at 100 nmol/L reversed apoptosis rate by 15%. Obestatin at 100 nmol/L induced rapid activation of PKB and reached the maximal effect at 30 min. Obestatin-induced activation of PKB phosphorylation was markedly blocked by LY294002. The percentage of apoptosis increased to 23% after LY294002 treatment.

Obestatin inhibits lipotoxicity-induced apoptosis in pancreatic β-cell line INS-1 through PI3K/PKB signal pathway and the peptide may have potential in treating diabetes.

To study the mechanism of ectopically fat deposition in the islets of high-fat-diet rat models and its relationship with islet beta-cell insulin resistance.

Forty healthy male SD rats (weight 160 to 170 g, 8-week old) were randomly assigned to the high-fat-diet (HF) and the normal diet (NC) groups. Rats of the HF group (n=20) were fed with high fat diet and rats of the NC group (n=20) were fed with normal diet. At 20 weeks, fasting blood glucose (FBG), fasting serum insulin (Ins), and triglyceride (TG) in the blood were determined. Glucose infusion rate (GIR) was measured by using euglycemic hyperinsulinemia clamp. The rats were then sacrificed, and the pancreatic islets were isolated and collected.TG in the pancreas was determined. The islet cell perfusion was conducted to evaluate the function of isle beta-cells. The mRNA expression of insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), phosphatidylinositol-3-kinase (PI3K), and glucose transporter-2 (GLUT-2) in islets were detected by real-time polymerase chain reaction. Student'st test and Pearson correlation analysis were used for data analysis.

The Ins and TG levels in the HF group were significantly higher than those in the NC group (t values were 2.73, 2.89, and 4.35; all P<0.01). The pancreas of high-diet group showed an increased storage of lipids. The GIR was significantly decreased in the HF group when compared with the NC group ((5.2±1.2) vs (13.6±1.7) mg·min^-1·kg^-1,t=6.48, P<0.01). The glucose stimulated insulin secretion was impaired in the high-fat-diet rats (t=7.36, P<0.01). The mRNA expressions of IRS-1, IRS-2, PI3K, and GLUT-2 were significantly decreased by 42.3% (t=8.53), 28.1% (t=3.94), 16.8% (t=2.79) and 22.9% (t=5.62, all P<0.05). There was a strongly negative correlation between TG level of the pancreas and IRS-1 or IRS-2 mRNA expression (r vales were -0.623 or -0.537, both P<0.05).

High-fat-diet rat models show an impaired expression of insulin signal transduction molecules in islet beta-cells, which may be correlated with the fat deposition in the pancreas.

To investigate the correlation between blood pressure and islet function condition in obese women with the same body composition.

First 88 obese women(BMI≥25.0 kg/m²) were divided into 3 groups according to their blood pressure: normal blood pressure group, prehypertension group, and hypertension group. Then, dual energy X-ray absorptiometry(DEXA) was used to measure their fat and lean mass, and calculate indexes of body composition(the fat and lean content of the whole body, trunk and four limbs). Next we calculated the area under the curve of insulin (AUCins) and acute insulin response (AIR) phase by intravenous glucose tolerance test(IVGTT). HOMA was used to calculate homeostasis model β-cell function index(HOMA2-%B), homeastasis model insulin sensitivity index (HOMA2-%S)and homeostasis model insulin resistance index (HOMA2-IR). Next, we built data models of hypertension and prehypertension, and used Binary Logistic regression to analyse risk factors.

There was no significant difference either among age, FPG, BMI, WHR and indexes of body composition of these three groups or among the HOMA2-%B, AUCins, and AIR. When increasing of blood pressure, 2 h PG, IVGTT ins0, TG, HOMA2-IR increased(P<0.05), but HOMA2-%S decreased (P<0.05), SBP showed a positive correlation with 2 h PG, TC, TG, IVGGT ins0, and HOMA2-IR, but a negative correlation with HOMA2-%S. DBP showed a positive correlation with 2 h PG, TG, and negative correlation with HOMA2-%S. Results of Logistic regression analysis showed that 2 h PG, HOMA2-IR, TG were in the equation in both models.

Insulin resistance is an important related risk factor for hypertension and even prehypertension in obese women with the same body composition.

To assess the relationship between brain-derived neurotrophic factor (BDNF) and depression in aged patients with type 2 diabetes (T2DM) and to investigate the etiology of depression in these patients.

A total of 241 patients, treated from March 2008 to December 2009, were included in this study. Based on the Center for Epidemiological Studies Depression Scale (CES-D) and Patient Health Questionnaire (PHQ-9) scales, the patients were divided into non-depression DM group (NDDM group, n=187) and depression DM group (DDM group, n=54). Fifty-two cases of healthy volunteers were set as control group (NC group). BDNF Val66Met polymorphism was determined with polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). Serum BDNF level was measured by enzyme linked immunosorbent assay(ELISA). The laboratory results were compared among the three groups by using independent-sample t test, one-way analysis of variance and SNK methods.

The morbidity rate of depression was 22.4% in this patients group, it was 17.7% in male and 27.1% in female. Compared with NDDM group, more patients were female and more complications occurred in DDM group(P<0.05), and DDM group also had a worse blood glucose control, a higher body mass index and a higher rate of loss of spouse (P<0.05). There was no significant differences in age and disease duration between the NDDM and DDM group(allP>0.05). There was significant differences in BDNF Val66Met polymorphism and allele (Val, Met) frequency among NC, NDDM, DDM groups (χ²=10.970, P<0.05), the frequency of allele Met in NC, NDDM and DDM group was 38.4%, 38.8% and 53.7%; and there were significant differences among the 3 groups(χ²=8.145, P<0.05). The score of PHQ-9 questionnaire in BDNF Val/Val, Val/Met and Met/Met groups was 3.2±0.9, 3.9±1.2 and 8.1±2.7, respectively; there was significant differences among the 3 groups (F=6.520, P<0.01). The serum BDNF level in NC, NDDM and DDM group was (86±10), (80±9) and (77±10) ng/L, respectively; there was significant differences among the 3 groups(F=28.450, P<0.01). Female, loss of spouse, high complication rate, poor blood glucose control, high body mass index and BDNF Val66Met polymorphism were predisposing factor to geriatric T2DM with depression on multivariate regression analysis.

The serum BDNF level in aged patients with T2DM complicated with depression is lower. BDNF Val66Met polymorphism contributes to the pathogenesy of geriatric T2DM with depression, and BDNF-Val66Met polymorphism is correlated with the severity of depression.

To evaluate the variation of fasting plasma ghrelin and its implication in adolescents.

In 2006, the study included 158 adolescents aged 13 to 15 years in Qinhuangdao.They were divided into two groups: group A(n=79, Ghrelin<1336.9 ng/L) and group B(n=79, Ghrelin≥1336.9 ng/L). Anthropometric measurements including height, weight and waist circumference(WC). Blood samples were collected and fasting plasma glucose(FPG), true insulin(TI), and Ghrelin were assayed.The methods used for analysis were t test, Pearson correlation and multiple linear regression.

(1) Group A had significantly higher levels of FPG, TI, insulin resistance index (HOMA-IR) than group B (P<0.05). Body mass index(BMI) and WC showed no significant difference between two groups(P>0.05). (2) Ghrelin showed negative correlation with FPG (r=-0.367, P=0.000) and ln(HOMA-IR)(r=-0.196, P<0.05). In multiple regression analyses, FPG(β=-337.2,P=0.000) and ln(HOMA-IR) (β=-160.0,P<0.05) were consistently associated with ghrelin.

Ghrelin correlated with FPG and HOMA-IR.The data suggests that the lower Ghrelin level may be a protective factor in adolescent with abnormal glucose metabolism.

To explore the effects of islet neogenesis-associated protein(INGAP)on proliferation and insulin secretion of pancreatic beta-cells.

INS-1 cells were purchased from Shanghai Bioleaf Biotech Company. INS-1 cells were co-cultured with or without 50 mg/L INGAP for 24 h. Insulin secretion was stimulated by treatment of cells with 2.8 or 16.7 mmol/L glucose for 1 h. The level of insulin in the supernatant was quantized using a rat insulin RIA kit. To examine the dose-response relationship between INGAP and quantity of INS-1 cells, the cells were treated with 1, 10, 25, 50, 100, 250, and 500 mg/L INGAP for 24 or 48 h. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) cell proliferation assay was adopted to detect the vitality of cells. The mRNA expression of PCNA, Cyclin d1, Cdk4, P27, p38MAPK, and JNK in INS-1 cells co-cultured with or without 50 mg/L INGAP for 24 h were examined by reverse transcription and polymerase chain reaction assay. The statistical significance was determined by Student'st test and One-way ANOVA.

In response to 2.8 mmol/L glucose, the insulin secreted by the co-culture group was more than the control group ((74±16) vs (39±9)mU/L, t=3.96, P<0.05), and under the condition of 16.7 mmol/L glucose, that was (78±9) vs (46±10) mU/L (t=4.72, P<0.01). MTT indicated a dose-response relationship between INGAP and quantity of INS-1 cells, and intervention for 48 h had a stronger effect than the 24 h. In contrast to the control group, the mRNA expressions of PCNA, Cyclin d1, and Cdk4 were up-regulated in INS-1 cells co-cultured with 50 mg/L INGAP (t values were 7.64, 5.98, and 12.87; all P<0.01); the mRNA expressions of P27, p38MAPK, and JNK were down-regulated (t values were 10.61, 27.64, and 2.95; all P<0.05).

INGAP increased the glucose-stimulated insulin secretion and the prolifration of INS-1 cells. The mechanism may contribute to changed expression of some genes that are related with cell cycle.

To study the effects of ribosomal protein S6 kinase 1 (S6K1) gene silencing in pathogenesis of hepatic insulin resistance.

Twenty-four healthy male db/db mice aged 9 weeks (body weight 44.5 to 48.2 g) were randomly assigned to the control group (n=12) and the study group (n=12). S6K1 short hairpin RNA recombinant adenovirus (S6K1Ax) was injected into the tail vein of db/db mice of the study group and U6 promoter recombinant adenovirus (pU6Ax) was injected into the control mice. At 6 days, those mice were randomly assigned to the fasting group (n=6) and the food-intake group (n=6). Insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2 (IRS-2) were determined by Western blot. Total RNAs were extracted to analyze gluconeogenic genes by using real-time quantitative reverse transcription polymerase chain reaction. Insulin was determined by enzyme-linked immunosorbent assay. Free fatty acids (FFA), triglyceride (TG), cholesterol and alanine aminotransferase were checked by colorimetry. All data were analyzed by One-way analysis of variance.

Compared with the control group, the protein expression of IRS-1 and IRS-2 of the S6K1Ax group was increased. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase) mRNA expression was descended (PGC1-α: 0.072±0.024 vs 0.028±0.012,F=7.58; PEPCK: 23.8±4.0 vs 12.3±2.4, F=5.76; G6Pase: 3.0±0.8 vs 1.5±0.4, F=9.15; all P<0.01). There was no difference in serum insulin between the control and the study group (t=1.26, P>0.05). Serum cholesterol of the study group was reduced in both fasting and food-intake state (F=15.48, P<0.01). Compared with the fasting control group, fasting blood FFA was decreased in fasting state of the study group (t=2.56, P<0.05).

Hepatic gluconeogenesis genes and serum FFA may reduce while IRS-1 and IRS-2 protein may increase in hepatic S6K1 gene silencing mice. These findings suggest that S6K1 may play an important role in hepatic insulin resistance.

To evaluate the effects of angiotensin Ⅱ on insulin signaling pathway in insulin-secreting NIT-1 cells in mice.

NIT-1 cells were cultured in the modified DMED, and then in the serum-free DMEM before assigned to the following 6 groups: angiotensin Ⅱ group (group A), insulin group (group B), angiotensin Ⅱ+ insulin group (group C), angiotensin Ⅱ+ insulin+ saralasin group (group D), angiotensin Ⅱ+ insulin+ Diphenyleneiodonium group (group E) and control group (group F). Expression of insulin receptor tyrosine phosphorylation (IR-β-Tyr), tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1-Tyr), serine phosphorylation of insulin receptor substrate-1 (IRS-1-Ser), and P47 phox were evaluated by Western blot. Level of H₂O₂ was detected by flow cytometry. Expression of insulin mRNA was evaluated by reverse transcript-polymerase chain reaction.One-way analysis of variance (ANOVA) and LSD test were used for data analysis.

Expression of IRS-1-Ser was higher in the group A than group F. The levels of IR-β-Tyr (1.22±0.26 vs 1.95±0.19, LSD test,P<0.01) and IRS-1-Tyr (0.74±0.18 vs 1.25±0.23,P<0.01) in group C were lower than those in group B, whereas the level of IRS-Ser was higher (1.11±0.17 vs 0.62±0.10,P<0.01). The expressions of IR-β-Tyr and IRS-1-Tyr in groups D and E were significantly increased when compared with group C, and the level of IRS-1-Ser changed adversely. The levels of H₂O₂ and P47 phox in groups A and C were significantly increased when compared with group F, and those in groups D and E were lower in comparison with group C. The expression of insulin mRNA was significantly increased in groups D and E than group C (group D vs group C: 0.80±0.17 vs 0.62±0.19, P<0.05; group E vs group C: 0.82±0.19 vs 0.62±0.19,P<0.01).

Angiotensin Ⅱ could increase the expression of IRS-1-Ser and inhibit insulin-stimulated IR-β-Tyr and IRS-1-Tyr in NIT-1 cells. Oxidative stress induced by nicotinamide adenine dinucleotide phosphate oxidase may play an important role in the effect of angiotensin Ⅱ in NIT-1 cells.

To observe the effect of adiponectin on the secretion of monocyte chemotactic protein(MCP-1) in rat proximal renal tubular epithelial cell(NRK-52E) in vitro.

Using DMEM medium with different concentrations of glucose and adiponectin to culture rat proximal tubular epithelial cells in vitro in five groups(four samples in each group, the experiment were repeated for 4 times): group A: DMEM medium with 5 mmol/L of glucose as control group; group B: DMEM medium with 30 mmol/L of glucose; group C: DMEM medium with 30 mmol/L of glucose and 1 mg/L of recombinant adiponectin; group D: DMEM medium with 30 mmol/L of glucose medium and 5 mg/L of recombinant adiponectin; group E: DMEM medium with 30 mmol/L of glucose medium and 10 mg/L of recombinant adiponectin. The reverse transcription time-polymerase chain reaction(RT-PCR) and Western blot methods were used to detect the expression of MCP-1 mRNA and protein in the 5 groups. The results were compared among the 5 groups. The t test was used when compared between two groups and analysis of variance was used in the comparison among multi-groups.

The expression of MCP-1 mRNA in group A was 0.247±0.005, it was 0.691±0.009 in group B and was significantly higher than that in group A(t=72.03, P<0.01); it was 0.425±0.013 in group C and was significantly higher than that in group A(t=46.31, P<0.05); it was 0.307±0.012 in group D and was higher than that in group A with no significant differences(t=73.24, P>0.05); it was 0.253±0.011 in group E and was similar with group A. There was significant differences in expression of MCP-1 mRNA among the groups with different concentrations of adiponectin(F=37.15, P<0.05). The expression of MCP-1 protein in group A was 10.25±0.03, it was 58.47±0.02 in group B and was significantly higher than that in group A (t=35.21, P<0.01); it was 35.86±0.05 in group C and was significantly lower than that in group B(t=48.26.21, P<0.05); it was 25.63±0.06 in group D and was significantly lower than that in group B(t=32.34, P<0.01); it was 21.53±0.03 in group E and was significantly lower than that in group B(F=42.26, P<0.05) and significantly higher than that in group A (t=64.28, P<0.01). There was significant differences in expression of MCP-1 protein among the groups with different concentrations of adiponectin(F=53.15, P<0.05).

Adiponectin could inhibit the highly expressed MCP-1 mRNA and protein induced by high glucose in rat proximal tubular epithelial cells in vitro in a dose-dependent manner.

Obesostatin, a 23-amino acid polypeptide coded by the same gene encoding somatotropin, can reduce feeding, reduce body mass, slow gastric emptying, and inhibit intestinal motility through the action of an orphan receptor 39 coupled to G protein^[1]。 There was a clear correlation between insulin and obestatin concentrations in pancreatic tissues^[2]。 It can be seen that obestatin may play a certain role in regulating energy and glucose metabolism. This study aimed to investigate the relationship between plasma obestatin levels and insulin resistance in patients with gestational diabetes mellitus.

Transient receptor potential channels are an important class of non-selective cation channels on cell membrane. Cosens and Manning, 1969;^[1]It was found that the visual system of the mutant Drosophila can produce a transient rather than sustained peak potential after continuous light stimulation, hence the name of the transient receptor potential channel. In mammals, researchers have found 28 transient receptor potential channel subtypes, which belong to six subfamilies according to the homology of amino acid sequences^[2]Among them, the transient receptor potential C channel is the earliest identified member of the transient receptor potential channel family and has the highest homology with the transient receptor potential channel of Drosophila. Since its first discovery in 1995, transient receptor potential C channel has been found to be expressed in many systems and tissues and organs such as nervous system, immune system, blood circulation system, kidney, lung, spleen and smooth muscle. At present, it is believed that the members of the transient receptor potential C channel family are the molecular basis of the calcium pool-manipulated and receptor-manipulated calcium channels on the cell membrane. As the main inflow channel of calcium ions, it not only participates in many physiological functions of the body, but also is related to many pathological processes.

glycogen synthase kinase (GSK) -3 is a silk/threonine kinase expressed in various tissues, originally named after its substrate is glycogen synthase. Current research results show that GSK-3 has many functions, which are closely related to intracellular glycogen metabolism, insulin signaling pathway, cell proliferation, nerve function, embryo development, tumorigenesis, etc. GSK-3 has a variety of different substrates, such as glycogen synthetase, tubulin, catenin, and others. Due to the diversity of functions of GSK-3, it is associated with a variety of diseases (such as diabetes, cancer, mental illness, Alzheimer's disease, etc.), and GSK-3 inhibitors are currently being actively developed as drugs for the treatment of these diseases.

In recent years, with the development of imaging technology, the use of molecular biology methods to identify specific imaging markers of pancreatic islet β cells has made great progress. A review is made by reviewing the relevant literature.

Intensive insulin therapy mainly includes two methods: multiple daily injections and continuous subcutaneous infusion (insulin pump infusion). Insulin pump administration can better simulate the physiological insulin secretion process and reduce the occurrence of hypoglycemic events. A study in patients with type 1 diabetes found that after 6 months of continuous subcutaneous insulin pump injection, patients had well-controlled blood glucose levels, along with a significant reduction in hypoglycemic events relative to baseline [baseline events: (16.2 ± 2.8) times/month, post-treatment: (8.7 ± 2.3) times/month], while hypoglycemic events increased relative to baseline in the multiple daily insulin injections group. In addition, total insulin dosage decreased in the continuous subcutaneous insulin injection group [baseline: (49.4 ± 3.3] U, post-treatment: (39.0 ± 4.6) U]^[1]。 Recent studies have pointed out that compared with multiple daily injections, intensive insulin pump therapy can improve the quality of life of patients^[2]。 Intensive insulin pump therapy reduces the occurrence of hypoglycemic events, reduces the daily dosage of insulin, reduces the cost to a certain extent, alleviates the fear of patients for severe hypoglycemic events, and makes patients more able to receive intensive insulin therapy, thus better controlling blood sugar levels. In addition, this treatment method, which removes the time limit of injection, effectively improves the freedom of the patient to participate in social activities, improves the quality of life of the patient, and also benefits the patient's family^[3]。

In recent years, the incidence of diabetes in children and adolescents has increased year by year due to many factors such as changes in diet structure, decreased physical activity and obesity, and its classification diagnosis has brought great confusion to clinicians. The diagnosis and treatment of this case experienced some changes during the admission process, which brought us some enlightenment. The report is as follows.

The latest survey data shows that the age-standardized prevalence of diabetes among adults over 20 years old in China is 9.7%^[1]。 The huge population of people with diabetes not only brings pain to individuals and families, but also causes a heavy burden to the country and society. At present, diabetes is still incurable, but effective blood sugar control can reduce or delay the occurrence and progression of diabetic complications^[2]。 In order to control blood glucose as early as possible, it is very important to diagnose diabetes early, give relevant knowledge education, provide guidance on self-management and lifestyle intervention, and carry out reasonable drug treatment. In recent years, evidence-based medicine has developed rapidly. According to the recent progress in diabetes research and the specific situation of China, the Diabetes Branch of Chinese Medical Association organized the compilation and release of the 2010 Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (hereinafter referred to as the "New Guidelines"). The new version of the guidelines gives norms and suggestions for the diagnosis, prevention, management and treatment of diabetes. Among them, the treatment part of premixed insulin is more specific than the previous edition of the guideline, and some modifications have been made. In the treatment of type 2 diabetes, premixed insulin is one of the most commonly used hypoglycemic drugs. In this paper, the specific application of premixed insulin in the new edition of the guidelines is interpreted.

Previous studies have shown that type 2 diabetes can increase the risk of cancer and mortality; Increased insulin-like growth factor-1 in patients with insulin resistance, hyperinsulinemia, and type 2 diabetes can promote tumor cell growth; High blood sugar levels may also be a risk factor for cancer. The purpose of this study was to systematically evaluate a recent large randomized controlled trial to explore the relationship between hyperglycemia and cancer prevalence and mortality.

Diabetic retinopathy (DR) is an important cause of blindness in diabetic patients. The purpose of this study was to investigate whether intensive hypoglycemic therapy combined with lipid-lowering and intensive antihypertensive therapy can delay the progression of DR.

Randomized controlled trials have demonstrated that lifestyle interventions, including exercise, reduce BMI and improve insulin resistance. Furthermore, 1 meta-analysis in 2007 showed that an increase of 2,183 steps per day of walking had no significant effect on fasting blood glucose; Another cohort study suggested that an increase of 2490 steps per day was not associated with plasma glucose levels. The purpose of this study was to investigate the relationship between daily walking number and body mass index, waist-to-hip ratio and insulin sensitivity for 5 years.

Adiponectin can improve insulin sensitivity, inhibit inflammation, and promote cell survival. Ceramide is a pheromone and pro-apoptotic lipid molecule for stress response. Blocking ceramide synthesis can significantly improve insulin sensitivity and prevent diabetes in obese mice. Is there a direct link between ceramide and adiponectin?

To evaluate the effect of eating high-protein snacks before breakfast on blood glucose after breakfast, the researchers selected 10 patients with type 2 diabetes who were treated with diet control and/or metformin. The patient had breakfast at 10 o'clock one morning (carbohydrates 51 g, fat 4.8 g, protein 5.8 g), and a snack was added 2 h before breakfast at 10 o'clock on another day (food intake was the same as before). The metabolic changes after breakfast were compared between the two days. The study found similar fasting blood glucose levels 2 h before breakfast on both days. The addition of snacks before breakfast led to a small peak in blood glucose level 60 min before breakfast, but the blood glucose concentration was significantly lower 2 h after meal, and the magnitude of blood glucose rise was significantly reduced. Blood glucose levels were identical in both groups 5 h after breakfast. There was no difference in fasting plasma free fatty acid concentration between the two days, but the plasma free fatty acid concentration decreased significantly before breakfast on snack day, which was correlated with the increase of blood glucose (r＝0.50，P＝0.013)。 Fasting serum insulin levels and fasting glucose oxidation rates were not significantly different between the two days, and fasting lipid oxidation rates were the same.

Leptin excites sympathetic nerves, promotes catecholamine release, and activates adipocyte beta-adrenergic receptors. Activated beta-adrenergic receptors can promote lipolysis and fatty acid oxidation by increasing intracellular cyclic adenosine phosphate (cAMP) levels, increase body's energy consumption, and inhibit the formation of obesity. Although this mechanism is still unknown, studies have shown that the disruption of catecholamine signaling pathway is an important cause of obesity.

Despite treatment with renin-angiotensin system inhibitors, patients with diabetes have an increased risk of progressive renal failure, which is associated with proteinuria levels. This study aimed to evaluate whether paricalcitol reduces proteinuria in patients with diabetic nephropathy.

Adipocytes are a group of highly specialized cells that play an important role in maintaining the energy balance of vertebrates. The increase in the size or number of fat cells is an important sign of obesity, and obesity has now become a global epidemic. Obesity is an important risk factor for the development and development of type 2 diabetes, cardiovascular disease and hypertension. Obesity and its associated diseases can lead to dysfunction of metabolic and endocrine-related gene expression regulatory mechanisms in adipocytes. Therefore, understanding the differentiation of adipocytes not only enables a deep understanding of the pathogenesis of metabolic diseases, but also identifies some proteins or pathways that may be targets for pharmaceutical intervention. Significant progress has been made in the understanding of the regulatory process of adipocyte differentiation, that is, the recognition of transcription factors that promote adipogenesis. White fat and brown fat have different origins, and different precursor cells are involved in forming these different types of adipose tissue. Some transcription factors, particularly peroxisome proliferator-activated receptor-gamma (PPAR-gamma), CAAAT enhancer binding protein (C/EBP), and some members of the Kruppel-like factor (KLF) family such as signal transduction and transcription activator 5 (STAT5) and SREBP-1c, have been shown to have a significant role in promoting adipogenesis. Other proteins have a negative role in regulating adipose tissue formation, including Wnts, KLFs, transcription factor family E2, C/EBP homologous proteins, delta binding protein A, ETO/MTG8, GATA, and forkhead transcription factor family members.

Nonalcoholic fatty liver disease often coexists with type 2 diabetes, but the incidence of nonalcoholic fatty liver disease in type 2 diabetic women with a history of gestational diabetes is unknown. This study aimed to investigate the incidence of nonalcoholic fatty liver disease and its risk factors in European women with a history of gestational diabetes mellitus.

At present, there are 1.2 billion overweight people and 300 million obese people worldwide, and the rate is doubling every five years. At the end of the 20th century, the World Health Organization declared that "obesity is increasingly becoming a global disease affecting human health". In China, the proportion of overweight adults has reached 20% ~30%, and the proportion of overweight adults in big cities is as high as 40%. Obesity can induce type 2 diabetes, cholecystitis, coronary heart disease, hypertension, osteoarthritis, breast cancer, colon cancer and other diseases. How to prevent and treat obesity and related metabolic diseases has become the main "social medicine" problem faced by countries in the world in the 21st century. Obesity and its associated metabolic diseases have long been thought to be caused by factors such as lifestyle, environment and genetics. Human central nervous system, adipose tissue and gastrointestinal tract jointly regulate the energy metabolism balance of the body. Nowadays, there is more and more evidence that the low level of inflammation caused by intestinal bacteria and their related endotoxemia is one of the important root causes of obesity and metabolic disorders.