Volume 09 · Issue 09 · 2017

Pancreatic islets, also known as Langerhans Island, are like dots of stars in the sky scattered throughout the pancreas. Although pancreatic islets account for only 1% to 2% of the total pancreatic volume, they are the core endocrine organ that regulates the body's energy metabolism and maintains blood sugar stability^[1]。 Nowadays, the incidence of diabetes remains high worldwide. Although obesity and insulin resistance are increasing simultaneously with the incidence of diabetes, we will still find in clinical work that some obese people are in a normal state of glucose metabolism for a considerable period of time, while a considerable number of non-obese people have developed type 2 diabetes. Therefore, the heterogeneity of islet dysfunction and islet failure and their dynamic changes, regardless of the presence or absence of obesity and/or insulin resistance, are the most unnegligible pathophysiological phenomena in the development of the natural course of diabetes.

Type 1 diabetes mellitus (T1DM) leads to absolute insufficient insulin secretion due to massive destruction of pancreatic islet β cells. Type 2 diabetes mellitus (T2DM) also has a process of gradual failure of pancreatic islet function. Both T1DM and T2DM patients with islet failure require multiple daily subcutaneous insulin replacement therapy. Although there are more and more types of insulin commercialized, long-term and unremitting efforts of patients are required to achieve the ideal glycemic control goal. On the other hand, even strict blood sugar control cannot completely avoid the occurrence and progression of diabetic complications, and too strict blood sugar control can easily induce hypoglycemia, which may increase the risk of cardiovascular events. To date, pancreatic transplantation or islet transplantation is the most effective method to completely correct insufficient insulin secretion in diabetic patients. However, pancreatic transplantation is difficult to be used as a routine treatment for diabetes because of a series of problems such as large surgical trauma and postoperative complications. The application of Edmonton protocol has significantly improved the clinical efficacy of islet transplantation, but the severe lack of donor islet tissue source has become the biggest obstacle restricting its promotion. Therefore, the strategies of islet beta cell regeneration therapy such as somatic cell reprogramming and stem cell transplantation become potential hopes to overcome diabetes^[1]。

Diabetes is one of the most common diseases that endanger human health. According to the International Diabetes Federation (IDF), the number of diabetic patients worldwide reached 366 million in 2011 and will increase to 552 million by 2030; China has become the fastest-growing country in the world, with the prevalence of diabetes reaching 11.6%, and nearly half of adults are in the pre-diabetic stage^[1]。 Diabetes has become the third largest non-communicable disease after tumor and cardiovascular and cerebrovascular diseases, which has caused a serious impact on national health and economic development. Diabetes is divided into type 1 diabetes, type 2 diabetes, gestational diabetes and other special types of diabetes. Although the causes are different, absolute and/or relative insulin deficiency caused by islet beta cell failure is the key cause of all types of diabetes^[2]。 In recent years, with the in-depth research on the development, differentiation (transdifferentiation and dedifferentiation), proliferation, apoptosis and functional regulation of pancreatic islet β cells and the further understanding of the changes of these factors in the development and development of diabetes, potential new targets that may be used to prevent and/or slow down pancreatic islet β cell failure continue to emerge. Developing and verifying the effectiveness and feasibility of these targets is one of the focuses of diabetes research at present.

To observe the effect of liraglutide in the long-term clinical remission after short-term continuous subcutaneous insulin infusion (CSII) in newly diagnosed type 2 diabetes mellitus (T2DM).

Eighty-five newly diagnosed T2DM patients from March 2014 to March 2015 in line with the inclusion criteria were discharged after two weeks' CSII intensive therapy. The patients were randomly divided into two groups according to the random number table method: the liraglutide group (40 cases) and the metformin group (45 cases), the patients discontinued drugs after 12 weeks' continuous monotherapy and lifestyle intervention. Fasting plasma glucose (FPG), 2-hours postprandial plasma glucose (2hPG), glycated hemoglobin A_1c (HbA_1c), body mass index (BMI), fasting C-peptide (FCP), 2-hours postprandial C-peptide (2hCP) and homeostasis model assessment of β cell function (HOMA-β) during the outpatient follow-up visit at 24th week were compared between the two groups. The up-mentioned indexes and clinical remission rate at 48th-week outpatient follow-up were compared between the two groups. The data were compared between the two groups by using t test when equal variance was confirmed with homogeneity test of variances.

After short-term intensive therapy, the FPG and 2hPG decreased significantly in comparison with those at hospitalization. There was no significant difference between the two groups in age, BMI, duration of disease and other general information. At the 24th week, there was no differences in FPG, HbA_1c and BMI between the two groups, the 2hPG was remarkably lower in the liraglutide group than that in the metformin group [(8.4±1.5) vs (11.2±2.2) mmol/L, t=4.26, P<0.05], while the FCP, 2hCP and HOMA-β were significantly lower in the liraglutide group than those in the metformin group [(2.2±0.3) vs (1.8±0.3) μg/L, (4.2±0.7) vs (3.6±0.5) μg/L, 76±7 vs 56±5,t=4.35, 4.70, 6.92, all P<0.05]. The FPG, 2hPG, HbA_1c, and BMI were notably lower in the liraglutide group than those in the metformin group at the 48th week [(7.3±1.3) vs (8.1±1.8) mmol/L, (9.5±1.4) vs (11.5±2.1) mmol/L, 6.9%±0.6% vs 7.3%±0.9%, (24.8±1.4) vs (26.2±2.1) kg/m², t=4.73-6.81, all P<0.05], while FCP, 2hCP and HOMA-β were significantly higher [(2.2±0.4) vs (1.8±0.2) μg/L, (3.9±0.8) vs (3.3±0.5) μg/L, 68±8 vs 50±5,t=9.05, 6.83, 4.92, all P<0.05]. Clinical remission rate was markedly higher in the liraglutide group than that in the metformin group [67.5% (27/40) vs 44.4% (20/45), χ ²=4.56, P<0.05].

Liraglutide is beneficial in the continuous improvement of pancreatic islet function and long-term clinical remission after intensive therapy in newly-diagnosed T2DM.

To understand diabetes related knowledge, attitude and behavior of urban and rural residents in Jiangsu Province.

In 2016, from March to June, the trained investigators used multi-stage stratified cluster sampling methods to conducted a face-to-face structured e-questionnaire survey of 7 689 urban and rural residents from 18-64 years old in 6 cities of Jiangsu Province, including demographic characteristics, diabetes-related knowledge and behavior of features. One way analysis of variance was used to compare between groups and SNK method was used for pairwise comparison.

The urban and rural residents' demographic characteristics, diabetes knowledge, the acquisition of related knowledge, as well as diet and smoking behavior existed significant differences between different regions in Jiangsu province. Respondents from Southern Jiangsu had higher correct awareness of diabetes knowledge than middle and Northern Jiangsu (χ²=10.867-79.401, all P<0.05) ; urban and rural residents in middle Jiangsu more focused on diabetes-related information (χ²=63.940, P<0.001) ; the smoking rate of urban and rural residents in Southern Jiangsu was higher than other region residents in Jiangsu Province (χ²=20.403, P<0.001) .

The different region residents in Jiangsu Province have different level of diabetes knowledge, attitude and behavior which shows that corresponding diabetes health education and behavior interventions should be taken in different area.

To develop a simple, cheap and effective method to isolate and purify islets in mouse.

Collagenase V was perfused into the pancreases by a self-made puncture needle inserted into the common bile duct, after digestion islets were isolated by a combined way of density gradient centrifugation and hand-pick. While the islets purified just by hand-pick was treated as control. Dithizone (DTZ) staining was applied to test the purity of islets, while the viability of islets was identified by Acridine orange/iodide c organism (AO/PI) staining and the islet function was tested by glucose(low glucose 2.8 mmol/L, high glucose 20.0 mmol/L) stimulated insulin secretion. Differences between the two groups were analyzed by student-t test.

It took 152 minutes to harvest the islets from five mice with self-made puncture needle and density gradient centrifugation, and it took 347 minutes with the traditional hand-pick method. The production of islets from each mouse using this new method was 95±8 and was slightly lower than that in control group (124±10, t=4.027, P=0.016); the purity with the new method was much higher than that in control group (92.6%±1.3% vs 79.2%±5.5%, t=4.075, P=0.015). There was no notable differences in islets viability between the two methods. Insulin secretion of the islets isolated by this combined method at low glucose (2.8 mmol/L) and high glucose (20.0 mmol/L) environment were (66±13) and (256±46) μg/L, separately ( t=4.075, P=0.002), it indicated that the islets isolated by this new method were sensitive for the change of glucose concentration.

The islets isolated by the combined way of density gradient centrifugation and hand-pick using self-made puncture needle maintain the production, purity, viability and islet function. In general, this method is a simple, cheap and effective way to isolate mouse islets.

To investigate the protective effect and mechanism of liraglutide on aorta endothelial cells in Zucker diabetic fatty (ZDF) rats.

Sixteen special pathogen free ZDF rats aged 10 weeks were adopted. The fasting plasma glucose (FPG) of them were greater than 11.1 mmol/L. They were divided into two groups by random number table and treated with subcutaneous injections liraglutide (group C) or saline (group B) 150 μg/kg, bid. Eight zucker lean rats were administered saline of the same volume (group A). Glycemic control was assessed by measurements of blood glucose levels every week. At the end of the experiment (after 6 weeks), the blood and the aorta were reserved. The oxidative stress marker malondialdehyde (MDA) and anti-oxidative enzyme glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) were measured. The inflammatory factor such as interleukin 6 (IL-6), vascular cell adhesion molecule 1 (VCAM-1) were evaluated by enzyme-linked immunosorbent assay (ELISA). The hematoxylin-eosin staining was used to observing the morphology of aorta. Western blotting was used for detecting the expression of epidermal growth factor receptor (EGFR), protein kinase B (Akt), phosphorylated Akt (p-Akt), endothelial nitric oxide synthase (eNOS) in aorta. The t test was performed in comparison between the two groups, while one way variance analysis for multiple groups comparison. The rank sum test was used when the data did not meet the normal distribution.

(1) After 6 weeks interventions, the level of MDA in group B [(3.8±1.2)μg/L] was increased compared with group A [(3.3±0.7)μg/L], which is decreased in group C[(1.2±0.5)μg/L,F=15.4, P<0.01]; SOD and GSH-Px were decreased in group B, which were increased in group C (F=4.7, 3.4, both P<0.05). (2)The level of IL-6 was increased in group B compared with group A (t= 2.95, P<0.05), and it was decreased in group C compared with group B, but there was no statistical difference (t=-0.60, P>0.05). The VCAM-1 was increased in group B [51(48-70)μg/L] compared with group A [29 (19-30)μg/L], and it was decreased in group C [19(11-25)μg/L] compared with group B (H=1.20, P<0.05). (3) TdT-mediated dUTP nick-end labeling (TUNEL) staining showed that there were apoptotic endothelial cells in aortic sections in group B but apoptotic cell was not found in group A and group C. (4)The expression of EGFR, p-Akt and eNOS were decreased in group B compared with group A, however, they were increased in group C (t=2.09, 2.10, 13.75, all P<0.05).

Liraglutide can alleviate oxidative stress in ZDF rats independent of the blood glucose and body weight, liraglutide plays a protective role on macrovascular endothelial cell by EGFR-PI3K/Akt-eNOS pathway.

To investigate the effects of berberine on intestinal glucose absorption and the underlying mechanisms.

Eight-ten weeks old male Sprague-Dawley rats were divided into control group and berberine group. Blood glucose, serum insulin and glucagon-like peptide-1 (GLP-1) were tested in oral glucose tolerance test (OGTT) and intraperitoneal glucose tolerance test (IPGTT) after berberine gavage. Glucose transport test in vitro was applied to determine the specific target glucose transporter of berberine. Jejunum segments were treated with glucose (100 mmol/L), berberine (25, 50, 100, 200 μmol/L), glucose transporter 2 (GLUT2) inhibitor phloretin and sodium/glucose co-transporter 1 (SGLT-1) inhibitor phloridzin, 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) was used to test the intestinal glucose transport ability. The expression and localization of GLUT2 and SGLT1 on intestinal epithelial cells membrane was tested by using Western blotting. Dunnett- t test was used to evaluate the statistical significance of difference between groups.

Compared with control group, blood glucose was significantly decreased at 15, 30, and 60 min in berberine group in OGTT (t=2.812, 2.648, 3.044, all P<0.05), however, there was no significant difference between two groups in IPGTT results. Compared with control group, serum insulin was significantly decreased at 15, 30, 60, and 120 min in berberine group (t=3.981, 3.583, 2.658, 2.707, all P<0.05), and serum GLP-1 level showed no significant difference between the two groups. Compared with glucose group (1.00±0.03), berberine (25, 50, 100, 200 μmol/L) treatment reduced glucose transport significantly (0.84±0.05, 0.62±0.04, 0.47±0.04, 0.46±0.04 respectively, q=2.847, 7.067, 9.712, 9.786, all P<0.05). Furthermore, there was no significant difference in glucose transport between the phloretin group and berberine+phloretin group (0.60±0.02 vs 0.58±0.02, q=0.68, P>0.05), but glucose transport decreased significantly in berberine+phloridzin group when compared with that in phloridzin group (0.42±0.02 vs 0.68±0.03, q=7.436, P<0.05). Western blotting showed that intestinal epithelial cells membrane GLUT2 localization decreased significantly in berberine group than that in control group (0.57±0.04 vs 1.00±0.00, t=9.808, P<0.05).

Berberine decreases intestinal glucose absorption through inhibiting intestinal epithelial cells membrane GLUT2 translocation.

In recent years, the incidence of papillary thyroid carcinoma (PTC) has increased significantly, and it is one of the fastest rising malignant tumors at present. Its etiology is complex, which may be related to gene mutation, excessive iodine intake, selenium deficiency and other reasons^[1]。 More and more studies have found that the incidence of PTC in diabetic patients is more pronounced than that in non-diabetic patients^[2]。 Wu^[3]It was reported that the prevalence of thyroid disease in diabetic patients reached 10.8%, which was significantly higher than that in the general population of 6.6%. The relative risk of thyroid cancer in diabetic patients compared with non-diabetic patients was 1.17 (95% confidence interval: 0.99~1.39)^[4]phosphoinositide-3-kinase (PI3K) and protein kinase B (Akt) signaling pathways play an important role in regulating cell proliferation and apoptosis. Our previous studies have found that the PI3K/Akt signaling pathway in vascular endothelial cells is inhibited under the action of high glucose, but may show different expression in thyroid cancer cells. In order to further understand the role and mechanism of PI3K/Akt signaling pathway in the proliferation of PTC cells promoted by glucose, we discussed the following.

autoimmune polyendocrine syndromes (APS) are rare in clinical practice. In this article, two patients were diagnosed with type 2 diabetes. After 7 years of follow-up, case 1 developed multiple autoimmune diseases of endocrine glands one after another. Case 2 was diagnosed by routine examination after admission to hospital. The clinical manifestations of APS are diverse, and the clinical symptoms of various endocrine gland damage may occur asynchronously, which is easy to be misdiagnosed. Clinical attention should be paid to the presence of multi-endocrine gland involvement and its immunological evidence to improve the diagnosis rate.

Islet injury is one of the most important pathophysiological mechanisms of diabetes mellitus. Type 1 diabetes mellitus (T1DM) is T cell-mediated specific immune damage against pancreatic islet cells. In addition to insulin resistance, islet damage is also an important factor in the pathogenesis of type 2 diabetes mellitus (T2DM). Whether T1DM or T2DM, islet injury plays a key role in the development and progression of the disease. Therefore, the accurate evaluation of islet injury is helpful to deepen the understanding of the pathological mechanism of diabetes mellitus and the precise treatment of diabetes mellitus. To explore accurate evaluation methods of islet injury and to find relevant biomarkers of islet injury is a direction worthy of attention in the research field of diabetes. This article mainly reviews the current assessment methods and related biomarkers of pancreatic islet injury.

Insulin resistance and islet beta cell dysfunction are the two main pathophysiological features of type 2 diabetes, and islet beta cell dysfunction is the key factor in the development of type 2 diabetes. Hyperglycemia and lipid metabolism disorders are the main causes of beta cell failure, known as glycotoxicity and lipotoxicity. Previous studies on lipotoxicity were mainly based on the close relationship between diabetes and obesity, and focused on the damaging effect of free fatty acids on pancreatic islet β cells. Recent studies suggest that the metabolic balance of β-cell cholesterol is a necessary condition for maintaining β-cell function. Increased cholesterol levels in beta cells caused by cholesterol metabolism disorders, obstruction of glycolytic processes, increased apoptosis of pancreatic islet beta cells, and decreased insulin secretion have been suggested as novel mechanisms of beta cell dysfunction. This paper introduces the current research progress on the relationship between cholesterol metabolism and pancreatic islet β cell function.

Diabetic foot refers to infection, ulceration, and deep tissue destruction of the foot due to diabetic peripheral neuropathy and/or peripheral vascular lesions. Diabetic foot wounds are complicated and difficult to treat. Due to the changes of glucose metabolism and oxidative stress, phagocytic function and antibacterial function are impaired in diabetic patients^[1]The wound is highly bacterial loaded, which increases procoagulant substances and local oxygen consumption in the blood, and aggravates local ischemia^[2], further affecting wound healing. Therefore, controlling infection and promoting wound healing are the key links in the treatment of diabetic foot. negative pressure wound therapy with instillation (NPWTi), as a new wound treatment method, has significant effects in controlling infection and promoting granulation tissue growth. This article will review the mechanism of action of NPWTi and review the clinical application of NPWTi in the treatment of diabetic foot.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease involved by genetic and environmental factors. Certain environmental factors act on individuals with genetic susceptibility, activating autoimmune responses that lead to islet beta cell destruction and functional failure. The environmental factors of T1DM pathogenesis mainly include milk feeding, vitamin D deficiency, virus infection, etc^[1]。 Studies have found that viral infections, especially enterovirus infections, play an important role in the pathogenesis of T1DM. This paper reviews the recent research on enterovirus infection and T1DM in recent years.

sodium glucose co-transporter-2 inhibitors (SGLT-2i) are a new class of hypoglycemic drugs that can selectively inhibit renal glucose reabsorption and increase urinary glucose excretion. SGLT-2i is highly selective and specific, and its glycosidic ligand competitively binds to the transporter glucose-binding end of the proximal convoluted tubules of the kidney, blocking the action of the transporter, reducing glucose reabsorption in the kidney, increasing glucose excretion in urine, and thus lowering blood glucose levels^[1]。