Volume 10 · Issue 08 · 2018

One of the main causes of glucose homeostasis imbalance in diabetes mellitus is islet dysfunction with or without insulin resistance. In the early stage of type 2 diabetes mellitus (T2DM), beta cells respond to the insulin demand caused by insulin resistance by increasing in size, number and secretory capacity. However, long-term overload will eventually lead to β cell failure and hyperglycemia. The study found that in this process, not only there is complex signal communication between the cells inside the islets, but also hormones, regulatory factors and metabolites released by peripheral tissues and organs such as fat, liver, skeletal muscle and intestine all participate in the communication with the islets (Figure 1）。 These results also provide new therapeutic ideas and targets for promoting β cell regeneration and restoring pancreatic islet function. The communication between pancreatic islets and multiple organs of the body is summarized.

Pancreatic islet alpha cells and beta cells secreted glucagon and insulin respectively to maintain homeostatic balance of glucose metabolism in the body. Dysfunction and decrease of islet β cells in diabetes mellitus are often accompanied by proliferation of islet α cells and hyperglucagonemia^[1]。 The traditional view is that the latter is an important factor that causes "high glucotoxicity" in diabetes, thus continuously damaging the function of pancreatic islet β cells. With the discovery of islet endogenous glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1 receptor, GLP-1R) signaling system and the dedifferentiation of islet β cells under metabolic stress, people have gained a new understanding of the functional role of islet α cells^[2]。 In recent years, many studies have shown that islet α cells are highly plastic and can be transdifferentiated into β cells spontaneously or induced under certain conditions, thus becoming a possible source of regaining functional islet β cell populations^[3]。 In addition to the classical paracrine regulatory pathways of insulin and glucagon in pancreatic islets, the activation of endogenous GLP-1/GLP-1R system mediated by α cells is an important adaptive compensatory response for the body to cope with metabolic stress damage, which reflects the regulation and protection of α cells to β cells^[4]。 This paper mainly describes the function of islet α cells and its research progress, in order to provide a new research direction for the regulation and protection strategy of islet β cells in diabetes mellitus and to regain the functional islet β cell population.

Diabetes mellitus is a metabolic disease characterized by elevated blood sugar. At present, it is believed that insufficient insulin secretion or insulin resistance is the key factor in the development of diabetes. Because pancreatic islets are the only insulin-secreting tissues in the body, the insulin-secreting beta cells in pancreatic islets have been widely concerned for a long time. Studying the number and function changes of pancreatic islets beta cells has been a hot spot in diabetes research. However, pancreatic islets are a cell mass composed of a variety of endocrine cells, and in addition to beta cells, alpha cells that secrete glucagon, delta cells that secrete somatostatin, epsilon cells that secrete ghrelin, PP cells that secrete pancreatic polypeptides, and the like are included. The regulation of cell circuits within islets is very important for maintaining the normal number and function of islet β cells. Therefore, in recent years, the dedifferentiation of islet β cells, their transdifferentiation with islet α cells or delta cells, and islet cell circuits have gradually become new research hotspots. The development of targeted intervention strategies based on these research hotspots may provide new ideas for the treatment of diabetes.

To investigate the expression levels and functional role of microRNA 766 (miR-766) in cardiomyocytes treated with high glucose conditions.

Cardiomyocytes were cultured with different concentrations of glucose levels at 5.0 mmol/L (Controls), 15, 25 or 35 mmol/L, respectively. The expression of miR-766 was detected by real-time PCR, apoptosis was detected by flow cytometry, and the expressions of exchange protein directly activated by cyclic adenylic acid isoform 1 (Epac-1), Bax and cleaved cysteinyl aspartate specific proteinase-3 (caspase-3) were determined by Western blot. The target gene of miR-766 calculated by bioinformatics was further determined by using dual luciferase system. T test was used for comparison between groups.

Compared with the controls, the expressions of miR-766 were significantly upregulated in different high glucose (HG)-stimulated cardiomyocytes (3.40±0.38, 4.61±0.34, 6.17±0.42 vs 0.97±0.04, t=11.131-21.493, all P<0.05). Inhibition of miR-766 in cardiomyocytes treated with HG resulted in reduced apoptosis [(16.43±0.31)% vs (26.45±0.31)%, t=-39.566, P<0.05]. Overexpression of miR-766 decreased the protein levels of Epac-1 (0.48±0.07 vs 1.00±0.12, t=-6.695, P<0.05), and inhibition of miR-766 increased the protein levels of Epac-1 (1.23±0.12 vs 0.70±0.10, t=5.884, P<0.05). Luciferase reporter assays showed that overexpression of miR-766 significantly decreased the luciferase activity of wild-type reporter, and inhibition of miR-766 significantly increased the luciferase activity of wild-type reporter (3.22±0.07 vs 5.01±0.96; 6.98±0.61 vs 5.01±0.96, t=-3.239--3.008, P<0.05). Moreover, transfection of miR-766 inhibitor could partly reverse the suppression of Epac-1 by HG in H9c2 cells (0.80±0.05 vs 0.53±0.05, t=6.810, P<0.05). Restoration of Epac-1 in miR-766-treated H9c2 cells reversed the effects of miR-766 on cleaved caspase-3 expression (0.67±0.07 vs 1.07±0.12, t=-5.050, P<0.05).

miR-766 plays an essential role in high glucose-induced cardiomyocyte apoptosis through regulating Epac-1 expression.

Dominant-negative effect refers to an interference pattern that the mutated protein does not only perform physiological function, but also inhibits activity of co-existing normal protein. The aim of this study is to investigate the role of dominant-negative effects in mutant INS-gene induced diabetes of youth (MIDY) caused by different types of insulin gene mutations.

The inhibition of co-expressed wild-type proinsulin secretion by three MIDY mutants was observed and a proinsulin-DelCys was introduced which carried MIDY mutations but couldn't form disulfide bond. There were 7 groups: 293T cells were co-transfected with wild-type human preproinsulin and mutant preproinsulins [as C(A7)Y group, G(B8)S group, R(SP6)H group and DelCys group]. Wild-type mouse preproinsulin and wild-type human preproinsulin were co-transfected as normal control group. Wild-type human preproinsulin and pCMS-EGFP plasmid were co-transfected as positive control group and wild-type mouse preproinsulin transfected 293T cells as negative control group. After 48 h, the media and cell were collected. Secreted human proinsulin was measured with human-specific proinsulin radioimmunoassay. Data were analyzed with one-way ANOVA andt test.

There was no statistically significant difference between the groups in the comparison of intracellular proinsulin levels (F=0.58, P>0.05). The differences of human proinsulin in cell culture medium among groups were statistically significant (F=297.57, P<0.01). Compared with normal control group, mutants C(A7)Y and G(B8)S blocked the secretion of co-expressed human proinsulin [(135.84±1.89) vs (29.28±6.85), (33.62±10.52) pmol/L, respectively, t=22.58, 21.66, all P<0.01]. There was no statistically significant difference between the normal control group and mutants R(SP6)H and DelCys groups (t=0.00, 0.39, all P>0.05).

MIDY mutants C(A7)Y and G(B8)S could induce the dominant-negative effects on co-existing wild-type proinsulin while R(SP6)H could not. Dominant-negative effect may be involved in the formation of intermolecular disulfide bond.

To investigate the expression of hippocampus proprotein convertase subtilisin/kexin type 9 (PCSK9) in type 2 diabetes mellitus (T2DM) rats and to explore its relationship with hippocampal injury in rats.

Nineteen healthy male Goto-Kakizaki (GK) rats were selected as model group [13 weeks old and (290±10)g] and seventeen healthy male wistar rats with the same age and genetic homology as model group were selected as control group [weight (290±10) g]. Weight, fasting blood glucose (FPG), glycosylated hemoglobinA_1c (HbA_1c) were measured after 2 and 10 weeks of feeding. Fasting C-Peptide (FCP), total cholesterol (TC) , triglycerides (TG), homeostasis model assessment-insulin resistance (HOMA-IR) were measured after 10 weeks of feeding. Using Morris water maze test to evaluate the learning and memory ability of rats after 10 weeks of feeding. Histopathological changes of hippocampus were observed by HE staining. Immunohistochemistry method was used to detect and analyze the expression levels of PCSK9 protein in hippocampus of each group, and Western blot method was used to detect and analyze the expression levels of PCSK9, cysteinyl aspartate specific proteinase caspase-3 (caspase-3) and B-cell lymphoma-2 (Bcl-2) protein. Using t test to compare the two groups.

FPG, HbA_1c, HOMA-IR and TC were all higher in the model group than those in the control group after 2 and 10 weeks of feeding (t=-29.305-7.813, P<0.05). FCP and weight were lower in the model group than those in the control group after 10 weeks of feeding (t=5.850, 9.574, all P<0.05). The weight and TG were similar in both groups after 2 weeks of feeding (t=1.062, -0.768, all P>0.05) . Morris water maze showed that compared with the control group, the escape latency of the model group rats was significantly prolonged in the navigation experiment after 10 weeks, and the quadrant residence time of the platform was significantly shortened in the space exploration experiment in the model group [ (24.2±3.7) vs (17.8±3.3) s, t=6.599, P<0.05]. The results of immunohistochemistry showed that the positive rates of PCSK9 immune-reactive neurons in model group increased than those in the control group significantly. Western blot results showed that the expression of PCSK9 and caspase-3 in hippocampus of model group increased significantly than that of control group (0.517±0.103 vs 0.806±0.114, 0.021±0.004 vs 0.136±0.019, t=-11.038, -19.598, both P<0.05) , the expression of Bcl-2 in hippocampus of model group was less than that of control group (t=8.099, P<0.05) .

The expression of PCSK9 increases in hippocampus of T2DM rats, which may be involved in the process of hippocampus injury in T2DM rats.

To investigate the prevalence and disease burden of diabetes in people aged 50 years or above in Xi'an.

Xi'an Community-based Management of Diabetes in the Elderly project (from June 2014 to September 2016) was a multicenter cross-sectional study using multistage, stratified cluster sampling methods. All individuals were given oral glucose tolerance tests. Standard World Health Organization criteria were used for the diagnosis of diabetes. Logistics analysis was used to examine the risk factors of diabetes prevalence.

A total of 3 001 individuals were included. The prevalence of diabetes was 26.3% (789/3 001) in total. It was 29.4% (319/1 086) and 24.5% (470/1 915) in men and women, respectively, 27.7%, 28.7% and 17.1% in urban, semi-urban and country, respectively, and 19.0%, 26.4% and 40.6% in 50-59 years age group, 60-69 years age group and 70 years or above age group, respectively. The awareness of diabetes was 57.8% (456/789) in total, 64.9% (207/319) in men and 53.0%(249/470) in women. The prevalence of self-reported diabetic chronic complications was 9.9% (78/789). Besides, 61.2% (483/789) of patients had hypertension, 46.3% (365/789) and 21.9% (173/789) had overweight and obesity, respectively, 66.4% (524/789) had dyslipidemia, and 70.1% (553/789) had metabolic syndrome. Logistics analysis showed that age, rural area and family history of diabetes were independent risk factors of diabetes prevalence (OR=0.617-3.815, all P<0.05).

People aged 50 years or above have a higher prevalence of diabetes than general population. Our study suggests the importance of screening and control of diabetes and its complications in the elderly population.

To assess the current stage of awareness and knowledge of Clinical Application Guide of Blood Glucose Monitoring in China (Edition 2015) among community nurses, hereby to provide a basis for carrying out standardized blood glucose monitoring training for community nurses.

A total of 415 clinical nurses were elected with cluster sampling method from community health service centers on May 30, 2017, including 198 nurses, 185 senior nurses, 30 supervisor nurses and more than 2 associate chief nurses. The data were collected and integrated into the database, categorical data is represented by the constituent ratio (%),variance analysis was used for comparison between groups.

Analysis total of 241 community nurses were lack of awareness of the guidelines and did not often recommend self-monitoring blood glucose (SMBG) prescriptions for patients, accounting for 58.08%. A smaller portion of responders (178 cases, 42.8%) fully disclosed SMBG related information A total number of 228 cases (54.94%) areaware of 6 self blood glucose monitoring programs recommended by the guide and their impact on diabetes management, accounting for. nurses from different department have varying cognitive scores on the guideline. Among them, general department nurses had the highest score [(20.26±3.00) points]. The differences among departments were statistically significant (F=8.631, P<0.05). Nurses with different working years had different cognitive scores on the guidelines. Among them, the scores of nurses working 11-15 years were the highest [(21.21±3.65) points]. The difference among groups was statistically significant (F=7.689, P<0.05).The average score of blood glucose monitoring was (20.21±3.90) points, 180 cases 43.37%. Scored either good or pass 235 cases (56.63%) failed. 172 cases (46.36%) of non-titled nurses achieved good or pass, 8 cases (18.18%) of titled nurses got good or pass.

The study results indicate that there is a definite gap in knowledge of of blood glucose monitoring applications amongst tcommunity nurses.

To explore whether changes of microalbuminuria are paralleled with the reduced glomerular filtration rate in type 2 diabetic patients.

A study was conducted in 1 184 type 2 diabetic patients from 27 Beijing community clinics between Apr. 2013 and Mar. 2015. Data of albumin/creatinine ratio (ACR), serum creatinine and lipid profiles were collected. Estimated glomerular filtration rate (eGFR) was evaluated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockcroft-Gault(CG), simplified Modification of Diet in Renal Disease (MDRD) formulas, and designated as eGFR_EPI, eGFR_CG, eGFR_MDRD, respectively. All data were expressed as ±s or median (interquartile range) as appropriate. The Student'st test or Mann-Whitney test was used for between-group comparison for continuous variables, and the Chi-square test for categorical variables. Spearman Rank Correlation was used to find the correlation between ACR and eGFR.

Of all type 2 diabetic patients aged (61±9) yrs, 754 were males (41.6%) and 1 060 were females (58.4%). ACR was not correlated with eGFR_EPI (r=-0.013), eGFR_CG (r=-0.014) or eGFR_MDRD (r=-0.007). The changes of microalbuminuria were not paralleled with the reduced glomerular filtration rate. Of patients with macroalbuminuria (defined as ACR≥300 mg/g), 83.3% (15/18) male patients and 50% (11/22) female patients had eGFR_EPI≥90 ml·min^-1· (1.73 m²) ^-1. Of patients with normal albuminuria (defined as ACR<22.1 mg/g in male and ACR<30.9 mg/g in female), 21% (101/482) male patients and 30.7% (238/776) female patients had eGFR_EPI<90 ml·min^-1· (1.73 m²) ^-1, and 2.5% (12/482) male patients and 3.4% (26/776) female patients had eGFR_EPI<60 ml·min^-1· (1.73 m²) ^-1.

Microalbuminuria can not fully reflect the reduced glomerular filtration rate in type 2 diabetic patients.

To explore the value of plasma procalcitonin (PCT) to lactate ratio in predicting the infection of patients with diabetic ketoacidosis (DKA).

A prospective cohort study of 81 DKA patients in department of endocrinology or emergency medicine of the hospital were divided into two groups. The infection group (n=30) and non-infection group (n=51). The following information was obtained from participants' records on admission: age, sex, body mass index (BMI), duration of type 2 diabetes mellitus (T2DM), and the types of diabetes. All patients were tested for PCT, lactate(Lac), high sensitive CRP (hsCRP), white blood cell, neutrophil percentage, PCT/Lac and creatinine within one hour after admission. The difference betneen 2 groups was analyzed by multiple factor Logistic regression analysis. Receiver operating characteristic curve was used to evaluate the predictive value of index to infection.

(1) There were significant differences of WBC, N%, PCT, Lac and PCT/Lac on admission between two groups (t=2.183, 2.069, 2.550, 2.144, 3.664, all P<0.05) . (2) The related factors were analyzed by logistic regression model, showing that WBC, N%, PCT, and PCT/Lac are still statistical differences between two groups (B=0.431, 0.551, 0.442, 0.264, 95%CI: 1.189-1.990, 1.076-1.592, 1.110-1.483, 1.181-1.798, all P<0.05) . (3) The area under the receiver operating characteristic curve was0.793±0.067, 0.715±0.073, 0.804±0.063, 0.908±0.046 respectively according to the level of the WBC, N%, PCT and PCT/Lac. The cutoff point of PCT/Lac was 0.25, the sensitivity and specificity increased up to 82.35% and 86.49%, respectively.

The higher PCT/Lac ratio is associated with higher infection risk in DKA patients. PCT/Lac equal to 0.25 can be used as a cutoff point.

To explore the clinical characteristics and prognosis of severe edema induced by exogenous insulin in type 1 diabetes mellitus.

A total of 32 patients with type 1 diabetes mellitus combined with severe insulin-induced edema were retrospectively analyzed in our hospital.

The number of female patients were significantly more than those of male patients with a female/male ratio 3∶1. There were 71.9% (23/32) patients younger than 20 years old and more than 70% (11/15) patients were underweight. 56.25% (18/32) patients were newly diagnosed type 1 diabetes mellitus, and 73.1% (19/26) patients were complicated with diabetic ketoacidosis. HbA_1c levels ranged from 12% to 19%, and 65% (13/20) patients received insulin treatment with the dosage ≤ 1.5 U·kg^-1·d^-1. Severe insulin-induced edema occurred within 1 week in 72% (18/25) patients. including 48.3%(14/29) patients with systemic edema, 51.7% (15/29) patients with peripheral edema and 17.2% (5/29) patients with serous effusion. Liver transaminase elevated in 20.7% (6/29) patients, and weight gained (because of edema) more than 10 kg in 30.4% (7/23) patients. Edema subsided spontaneously without diuretics therapy in 53.1% (17/32) patients, and edema subsided within 2 weeks in 66.7% (18/27) patients.

Females, underweight, poor blood glucose control and diabetic ketoacidosis occurr more frequently in type 1 diabetic patients with severe insulin-induced edema. Severe insulin-induced edema is transient and self-limiting, and can subside with or without diuretics therapy.

extracellular vesicles (EVs) were first defined in 1980 as circulating, membrane-encapsulated nanoscale vesicles (containing microvesicles, exosomes, apoptotic bodies, etc.) that are released from the endosomal pathway of cells. Its contents include proteins, lipids, nucleic acids, etc., which can affect the phenotype and function of target cells. Recent studies have found that EVs is closely related to the occurrence and development of diabetes mellitus, and the content and fluctuation of EVs in circulation can be used as potential biomarkers for the diagnosis and prognosis of diabetes mellitus and related complications. Pancreatic islets are the core organs that regulate blood glucose. More and more evidence supports that EVs mediates the communication and communication between islets and other organs to regulate islet function. This article will briefly summarize the basic characteristics of EVs, their expression in diabetes mellitus and the regulation of pancreatic islet function.

Studies have confirmed that the pathogenesis of type 2 diabetes mellitus (T2DM) is closely related to inflammation. Some scholars have pointed out that chronic systemic inflammation of visceral fat is an important cause of obesity-induced insulin resistance^[1,2]。 Therefore, suppression of inflammation is an important therapeutic strategy for the treatment of T2DM. Psoriasis is a common skin condition characterized by chronic inflammation with varying degrees of desquamation, erythema, itching, and plaque formation. Studies have shown that helper T cell (Th) -1, Th-17 and inflammatory cytokines such as interleukin (IL) -17, IL-22, tumor necrosis factor (TNF) -α are involved in the pathogenesis of psoriasis^[3]。 Recently, a commonly used hypoglycemic drug, glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), can exert certain anti-inflammatory effects by reducing the production of inflammatory cytokines and immune cells in tissues^[4]。 The therapeutic effect of GLP-1 RAs in T2DM complicated with psoriasis and its possible mechanism will be described in this article.

high-fat and low-carbohydrate diet, or ketogenic diet, is a kind of diet that is mainly high-fat and low-carbohydrate, plus an appropriate amount of protein. This diet was first evolved from the hunger treatment (that is, fasting without water) to treat epilepsy, and was developed by American physician Wilder^[1]Founded in 1921, he discovered that the ketogenic diet can make the body produce ketone bodies to mimic the state of hunger, which can effectively inhibit the occurrence of epilepsy. Subsequently, this diet was widely used in the treatment of epilepsy, especially for the treatment of refractory epilepsy in children. It has a very significant effect, and can even replace drug treatment under certain circumstances^[2]。 With the deepening of research on high-fat and low-carbon ketogenic diet, its application is also constantly expanded. At present, it has been used in the treatment of diabetes, neurological diseases, tumors and other diseases. This article mainly summarizes the application and current progress of high-fat and low-carbon ketogenic diet and related dietary regimens in the treatment of diabetes.

Heart failure (HF) and type 2 diabetes mellitus (T2DM) are mutual risk factors^[1,2]Therefore, clinically, heart failure combined with T2DM is very common. The prevalence of T2DM in patients with heart failure is 10% ~23%^[3]The prevalence of heart failure in patients with T2DM is 40% to 50%^[4]and heart failure is the second largest initial manifestation of cardiovascular disease (CVD) in patients with T2DM^[5]。 The 5-year mortality rate of heart failure is as high as 40% to 50%^[6]The risk of cardiovascular death is further increased when T2DM is combined with heart failure: for patients with heart failure with preserved ejection fraction (HfpEF, that is, left ventricular ejection fraction ≥50%), the unadjusted hazard ratio (hazard ratio,HR) was 2.0 (95% CI：1.70，2.36)； For heart failure with reduced ejection fraction (HfrEF, left ventricular ejection fraction<40%) of patients, whose uncorrectedHRwas 1.60 (1.44, 1.77)^[7,8]。