Volume 06 · Issue 03 · 2014

In the past few decades, with the change of environment and living standard, the incidence of obesity has increased greatly, and it has become an important disease that threatens human health. Obesity can produce a range of health problems, such as hypertension, type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease, obstructive sleep apnea syndrome and cancer. While genetic factors can determine a person's obesity propensity, recent findings suggest significant differences in the structure of the gut flora between healthy people and those with obesity or type 2 diabetes^[1], intestinal flora may play an important role in the occurrence of obesity and its associated diseases.

For endocrinologists, diabetes is a chronic disease that requires lifelong medication, and the dose and type of drugs required will also increase with the course of the disease and the progression of the disease. Even so, the compliance rate of diabetes is still not optimistic, and the compliance rate in China is less than 40%^[1]And less than 50% in European and American countries [glycated hemoglobin (HbA1c)<7%]^[2]As for the proportion of patients whose blood sugar, blood pressure and blood lipids meet the standards at the same time, it is even lower. However, surgical treatment of type 2 diabetes is an unexpected gain of foreign scholars after bariatric surgery for morbid (extremely severe) obese patients. Pories et al.^[3]In the 14-year follow-up observation of patients with morbid obesity after gastric bypass surgery, it was found that the surgery can not only effectively lose weight, but also effectively control blood sugar, and some of them even "recover" (no longer need hypoglycemic drugs). Meta-analysis found that bariatric surgery resulted in remission of 60% to 85% of diabetes, hypertension, dyslipidemia and sleep apnea syndrome^[4,5]While also significantly reducing the risk of death associated with diabetes^[6,7]Reduce the cost of medication and overall health management^[8,9]。 This is an amazing treatment in the history of diabetes treatment. Therefore, in 2009, the American Diabetes Association (ADA) officially listed bariatric surgery (metabolic surgery) as one of the treatment measures for obesity with type 2 diabetes in the diagnosis and treatment guidelines for type 2 diabetes^[10]。 In 2011, the International Diabetes Federation (IDF) also officially recognized metabolic surgery as a treatment for type 2 diabetes with obesity^[11]。 In the same year, the Diabetology Branch (CDS) of the Chinese Medical Association and the Surgery Branch of the Chinese Medical Association also recognized metabolic surgery as one of the methods to treat type 2 diabetes with obesity^[12]。

The prevalence of obesity and type 2 diabetes has become a major global public health challenge, and the treatment of type 2 diabetes combined with obesity makes it even more challenging. In the past three decades, clinical practice has shown that obese patients with diabetes have obviously improved their diabetes after undergoing bariatric surgery, besides weight loss, most of them can effectively control blood sugar within the normal range without medication, and the curative effect is obviously better than conventional medical treatment^[1,2,3]And the associated comorbidities such as metabolic syndrome and hypertension have also been significantly alleviated^[4]It has even been reported that the incidence of tumors in such patients has been significantly reduced^[5]。 The effectiveness of bariatric surgery for diabetes has been fully recognized in clinical practice. In recent years, many professional societies have issued statements, expert consensus or guidelines listing bariatric surgery as a treatment for diabetic patients with morbid obesity^[6,7,8]。 In 2011, the International Diabetes Federation (IDF) named gastric bypass and biliopancreatic shunt, which have the highest diabetes remission rate among all types of bariatric surgery, as metabolic surgery^[9]。 This makes the traditional concept in the field of diabetes treatment changing. More and more metabolic endocrinologists and gastrointestinal surgeons are involved in the clinical practice of diabetic metabolic surgery. However, it is reported that the remission rate of diabetes after surgical treatment is quite different (42% ~95%)^[1,3]All the reasons, regional and ethnic differences, as well as differences in preoperative evaluation, mastery of surgical indications, selection of surgical procedures, and management of comprehensive postoperative treatment may all be factors affecting the surgical treatment effect.

To investigate the effect of Roux-en-Y gastric bypass (RYGB) on glucose and lipid metabolism and systemic inflammation levels in spontaneous Zucker Diabetic Fatty (ZDF) rats.

Thirty male ZDF rats were randomly divided to three groups: RYGB surgery group (n=10), sham surgery pair-fed (PF) group (n=10) and sham surgery ad libitum fed (AL) group (n=10). Body weight, food intake was monitored. Oral glucose tolerance test, serum lipid level, liver transaminases, TNF-α, IL-1β and MCP-1 were measured before and 10-week after surgery. Then, rats were sacrificed. The epididymal fat were taken from all groups of rats. The mRNA expression of TNF-α, IL-1β and MCP-1 in epididymal fat of rats were detected using RT-PCR method. The data was analyzed byt test and analysis of variance.

Oral glucose tolerance test showed that blood glucose were significantly different among the RYGB group, AL group and PF group after 10 weeks postoperatively (FPG (6.8±0.5), (8.7±2.2), (20.6±3.0) mmol/L, F=12.4, P<0.05, 30 min (14.0±0.8), (19.1±4.3), (31.7±0.9) mmol/L,F=20.1, P<0.05, 60 min (15.4±1.1), (20.2±7.1), (33.0±0.3) mmol/L,F=22.5, P<0.05, 90 min (13.2±0.6), (20.0±5.8), (32.4±0.4) mmol/L,F=14.7, P<0.05, 120 min (8.3±0.3), (14.0±5.2), (29.1±1.2) mmol/L,F=20.5, P<0.05). Serum total cholesterol (TC) and free fatty acids (FFA) was decreased in the RYGB group, compared with PF and AL controls (TC (3.82±0.13)vs (4.10±0.37) vs (5.25±0.25) mmol/L, F=15.3, FFA (0.47±0.14) vs (0.93±0.08) vs (0.78±0.06) mmol/L, F=3.4, both P<0.05). And liver transaminases (ALT and AST) levels in RYGB group were lower than AL group, but higher than PF group (ALT (129±28)vs (67±7) vs (726±160) mmol/L, F=15.1, AST (208±26) vs (124±10) vs (673±209) mmol/L, F=5.9, both P<0.05) and the serum levels of TNF-α and IL-1βin RYGB group also decreased, compared with those in AL group (TNF-α (124±23)vs (532±52) mmol/L, t=5.8; IL-1β (61±16)vs (250±32) mmol/L, t=4.3, both P<0.05). The mRNA expression of above two factors coincided with the serum levels in three groups. However, MCP-1 expression were similar among the groups (P>0.05 all above).

RYGB can significantly moderate glucose homeostasis and lipid metabolism, decrease fatty liver and systemic inflammation levels in the ZDF rat model. This effect is not reliable to the reduction of food intake.

This single center, randomized, open-label study was aimed to compare the efficacy and safety of liraglutide and sitagliptin in over-weight and obese type 2 diabetic patients.

Eighty-six type 2 diabetes in-patients with body mass index(BMI)>25 kg/m² from April to October 2012 were enrolled.Subjects were numberally randomly assigned to liraglutide group(n=40) or sitagliptin group(n=46), and all receiving metformin (1 000 mg/d) simultaneously. Fasting plasma glucose(FPG), postprandial plasma glucose (PPG), HbA1c, body weight, waistline, blood pressure, triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol(LDL-C), live function, kidney function and 24-hour urine microalbumin (UMA) of each patient were measured before and 4, 12, 24 weeks after treatment.Incidence of hypoglycemia and other side effects are recorded during treatment.T test and repeat measurement data variance analysis were used to analyze the data.

(1)Compared to the baseline, after 24-week treatment, the levels of FPG, PPG and HbA1c were all decreased in liraglutide group, as well as in sitagliptin group. No difference was shown between the two groups(all P>0.05). (2) Body weight reduced in liraglutide group ((80±7)vs(85±8) kg,t=2.9, P<0.05)and in sitagliptin group ((82±7)vs(84±7)kg,t=2.78, P<0.05). There was statistical significance between the two groups after 24-week treatment(t=-3.5, P<0.05). (3)The mean waist circumference reduction in liraglutide group was ((101±7) vs(106±8)cm,t=13.35, P<0.05) greater than in sitagliptin group ((102±6) vs (105±6) cm,t=3.3, P<0.05). There was statistical significance between the two groups(t=-3.1, P<0.05). (4) After 24-week treatment, SBP of liraglutide group decreased from (143±6) to (138±7) mmHg(1 mmHg=0.133 kPa,t=3.69, P<0.05), while that of sitagliptin group decreased from (141±5) to (139±4) mmHg.There was statistical significance between the two groups(t=2.8, P<0.05). We can see statistical difference of SBP between two groups at week 24 (t=-3.1, P<0.05). After 24-week treatment, DBP of liraglutide group decreased from (93±2) to (89±2 )mmHg (t=2.6, P<0.05). while that of sitagliptin group decreased from (92±3) to (89±3) mmHg (t=3.5, P<0.05). But there was no significant difference in DBP between the two groups(t=1.64, P>0.05). (5) More people in liraglutide group felt gastrointestinal discomfort than in sitagliptin group(30% vs 4.3%,t=2.86, P<0.05).

Our results imply liraglutide with metformin and sitagliptin with metformin has equal capability of reduction of blood glucose and HbA1c. The former one is superior to the latter one on control of body weight, waistline and blood pressure, and sitagliptin leads to fewer gastrointestinal effects than liraglutide.

To investigate the relationship between trunk fat/lean tissue and metabolic syndrome in over weight or obese premenopausal women.

136 premenopausal overweight or obese women (BMI≥25.0 kg/m²) was enrolled from our outpatients from January 2006 to December 2012. Dual energy x-ray absorptiometry (DEXA) was used to measure fat, muscle mass, and calculated trunk fat content (%TF), leg muscle content (%LM), and trunk/leg muscle ratio (TMR). Then they were divided into 4 groups, according to quartile of %TF, %LM, TMR. Metabolic syndrome was in the diagnosis of criteria as Chinese Diabetes Society recommended. The relevance ratio of hypertension, hyperglycemia, dyslipidemia and metabolic syndrome were compared by chi-square test, trends analyzed by the chi-square test for linear trend and the influence that they have on metabolic syndrome were analyzed by logistic regression analysis. Spearman rank correlation was used in evaluating of the relationship.

(1) the detection rate of hypertension increases with %TF (=9.042, = 6.147; P<0.05); with the increasing of TMR, the detection rate of hypertension and dyslipidemia and 3 metabolic disorder components were increasing gradually (=8.628, 9.890, 9.589; =7.556, 9.017, 6.445; P<0.05 all above). And all of them make no difference with increasing of %LM (P>0.05 all above). (2) The results of logistic regression analysis showed that both %TF and TMR entered the regression equation for hypertension, dyslipidemia and metabolic syndrome, and TMR also entered the regression equation for hyperglycemia. (3) Hypertension, dyslipidemia, hyperglycemia and metabolic syndrome were all positively correlated with TMR (r=0.218, 0.218, 0.209, 0.204, P<0.05 all above). %LM was not correlated with all of them (P>0.05). Hypertension, dyslipidemia and metabolic syndrome were all positively correlated with %TF (r=0.174, 0.171, 0.175, P<0.05 all above).

Abnormal accumulation of trunk fat is a risk factor associated with metabolic syndrome in overweight or obese premenopausal women, and the association can increase with leg muscle decreasing.

To explore the characteristics of impaired glucoregulation during different treatment stages in patients with Graves' disease from the coastal area of Shandong Province.

A total of 106 patients with Graves' disease from Qilu Hospital of Shandong University were enrolled in this study and divided into 3 groups according to different treatment stages: primary treatment period group (GD1 group), treatment period group (GD2 group) and titration period group (GD3 group). Thirty healthy person were taken as normal control (NC group). All patients were treated by antithyroid drugs (ATD) for 6 months. On baseline and after treatment, the levels of blood glucose and serum insulin were evaluated, the values of early phase insulin secretion index (ΔI₃₀/ΔG₃₀), glucose area under curve (GAUC) and insulin area under curve(INSAUC) were calculated by oral glucose tolerance test(OGTT) and insulin release test(InsRT) in all patients. Data were analyzed by the one-way analysis of variance (ANOVA).

The fasting blood glucose levels were all lower in GD groups than that in NC group (F=29.85, P<0.05), on baseline; and the levels of blood glucose and insulin in GD groups after OGTT were markedly higher than those in the NC group(F=22.54, 87.96, both P<0.05). Compared with NC group, the values of ΔI₃₀/ΔG₃₀ in GD groups decreased significantly (F=17.22, P<0.05), however, the values of GAUC, INSAUC of GD groups increased significantly (F=79.09, 112.77, both P<0.05). After the treatment, the levels of blood glucose and insulin decreased significantly (F=17.19, 48.88, both P<0.05), the values of GAUC, INSAUC of GD groups decreased significantly(F=53.08, 96.98, both P<0.05).

The glucoregulation is impaired in patients with Graves' disease from the coastal area of Shandong Province. The impaired glucoregulation manifests as lower fasting blood glucose, impaired glucose tolerance and β cell dysfunction, and characterized by impaired early-phases insulin secretion and hyperinsulinemia. Normalization of thyroid function improves the impaired glucoregulation, but the dysfunction of islet βcell will last for a long period.

To investigate the differentiation effect of liraglutide on bone marrow mesenchymal stem cells (BM-MSCs) into insulin producing cells (IPCs) in vitro, and further to observe the therapeutic action of IPCs on type 1 diabetes(T1DM) rats.

BM-MSCs were separated and purified by density gradient centrifugation combined with attachment culture method in vitro, and they were divided into control group, high glucose with nicotinamide induction group, glucagon-like peptide 1 (GLP-1) induction group and liraglutide induction group. The morphological change of cells was observed by inverted microscope during induction, and they were confirmed by dithizone (DTZ) staining. Gene measurement of Nestin, pancreatic and duodenal homeobox 1(PDX-1), glucokinase(GK), glucose transporter-2(Glut-2), insulin and glucagon were tested by Real-time PCR. Protein expression of insulin and glucagon were detected by cell immunofluorescence. Thirty SD rats (weight 180-220 g) were injected 60 mg/kg of streptozotocin to establish the type 1 diabetes model, then they were randomly divided into control group (group T1DM, n=8), BM-MSCs transplantation group (group BM-MSCs, n=9)and BM-MSCs induced by liraglutide transplantation group (group LIRA+ BM-MSCs, n=9). Random blood glucose was monitored regularly during the treatment for 8 weeks. In addition, the intraperitoneal injection of glucose tolerance test (IPGTT) was carried out after the blood glucose was stable, by which another 4 normal rats were selected as control.

(1) In vitro, BM-MSCs showed distinct tendency to form clumps at confluence when liraglutide was added, and dithizone staining was positive. Compared to high glucose with nicotinamide induction group, the mRNA expression of Nestin was lower in liraglutide induction group (0.003 8±0.000 4 vs 0.007 5±0.003 0), while the level of insulin(0.000 20±0.000 03 vs 0.000 08±0.000 02)and glucagon(0.001 1±0.000 4 vs 0.000 7±0.000 1, F=7.26, 10.06, 4.92, all P<0.05) was higher. The mRNA expression of PDX-1, Glut-2, GK was also increased. The expressions of insulin and glucagon protein were positive in liraglutide and GLP-1 induction group. (2) In vivo, compared to group T1DM, the concentration of randomly blood glucose was significantly decreased both in group LIRA+ BM-MSCs and group BM-MSCs((28.0±1.2), (8.9±1.1), (14.5±0.9)mmol/L, respectively,F=719.61, all P<0.05). IPGTT showed blood glucose reached to a peak at 30th minutes and dropped to fasting glucose at 150th minutes in group LIRA+ BM-MSCs, which was similar to normal.

BM-MSCs could be enhanced to differentiate into IPCs by liraglutide in vitro, and further to make effect by IPCs in vivo.

To observe changes of β/α cell mass, cell cycle, Survivin expression of pancreatic islets in mice during pregnancy and changes in INS-1 cell proliferation after Survivin knockdown with prolactin stimulation, and explore the relationship between Survivin and islet cell proliferation.

β/α cell mass of female C57BL/6 mice islets at non-pregnancy (NP), pregnant day 10.5, 14.5, 18.5 (P10.5, P14.5, P18.5) and after parturition day 4, 8 (AP4, AP8) in mice was detected by immunohistochemistry. Pancreatic islets were digested and isolated by collagenase. Cell cycle was detected by flow cytometry. The expression of Survivin mRNA and protein were detected by real-time quantitative polymerase chain reaction (PCR) and Western blotting methods. INS-1 cells were transfected with siRNA mediated by liposome to knockdown Survivin expression, and the change of cell cycle with prolactin stimulation was detected. One-way analysis of variance or LSD test was used for data analysis.

During pregnancy, islet β/α cell mass markedly increased, peaking at P18.5. Compared with NP, β cell mass increased for 2.1 times (3.84±0.38 vs 1.81±0.09, t=4.75, P<0.05) and α cell mass increased for 1.6 times (0.92±0.13 vs 0.56±0.08,t=2.69, P<0.05), then both of them returned to NP level at AP8. Cell cycle analysis showed that the proliferation of islet cells increased significantly during pregnancy, peaking at P14.5. Compared with NP, the proliferation index increased for 2.7 times (23.07±1.88 vs 7.72±1.12,t=10.89, P<0.05), and returned to NP level after parturition. The mRNA level of Survivin during pregnancy was much higher than that at NP, peaking at P14.5 and increased for 6.7 times when compared with that in NP (6.69±1.61 vs 1.00±0.00,t=4.57, P<0.05), and reduced to NP level after parturition. Western blotting showed that Survivin protein expressed at P10.5, peaked at P14.5, and increased for 3.6 times when compared with that in P10.5 (3.63±0.26 vs 1.00±0.00,t=9.98, P<0.05), decreased since P18.5, and disappeared at P20.5. Prolactin could markedly stimulate INS-1 cell proliferation. However, Survivin knockdown in INS-1 cells by siRNA blocked cell proliferation with prolactin stimulation.

The proliferation of islet cells increases significantly during pregnancy in mice, accompanying with dynamic expression of Survivin. Survivin mediates the proliferative effect of prolactin on islet β cells.

A total of 6 785 female participants were collected, containing 3 170 orthoglycemic women(NC group), 2 035 impaired glucose regulation women(IGR group) and 1 580 diabetic women (DM group). The clinical data were investigated, including the number of children, age, serum lipids, blood pressure, waist and hip circumference, smoking, drinking, and so on. The association between increasing number of children and glucose metabolic status was evaluated by stepwise logistic regression. Among the NC group (n=3 170), IGR group (n=2 035) and DM group (n=1 580), there was significant difference in the number of children that NC group has least children with a mean of 4(0, 8), and DM group has most children with a mean of 5(0, 10). In a full model, after controlling other factors, the number of children had a significant positive influence on the diabetes risk of middle-aged women (OR: 1.115, 95%CI: 0.063-0.156, P<0.05). The number of children was associated with IGR and DM in middle-aged women, and this relationship seemed to suggest grand multiparity may be one risk factor of IGR and DM in middle-aged women.

Obesity refers to chronic metabolic diseases in which the volume and number of fat cells in the body increase, the percentage of body fat in body weight increases abnormally, or excessive deposition in some local areas (such as the abdomen), which has a certain impact on health. The pathogenesis of obesity is very complex, and the interaction between environmental factors and genetic susceptibility dominates. Recent genome-wide association studies (GWAS) have discovered a number of new genes related to obesity and energy metabolism, such as transmembrane protein 18, glucosamine-6-phosphate deaminase, potassium-containing channel tetramerization domain 15 and SH2 adaptor protein 1 (SH2B1), etc. However, most of the specific functions are still unclear. This paper focuses on the role of SH2B1 in energy metabolism, and the correlation between its gene polymorphism and metabolic indexes such as obesity and insulin resistance.

SHBG is mainly synthesized and secreted by the liver under the regulation of hormones and some cytokines. SHBG in human blood forms a homodimeric glycoprotein from two polypeptide sequence subunits with a molecular weight of approximately 45 000 in size, whose stability in blood is influenced by sex hormone ligands, metal ions, in particular calcium ions, which are necessary for maintaining the dimeric form. In the circulation, SHBG has a high affinity for sex hormones. SHBG binds most of the sex hormones to make them inactive and released after reaching the target tissue. In comparison, SHBG binds more strongly to androgens; Of the natural and synthetic sex hormones, the strongest binding to SHBG is dihydrotestosterone^[1]。

Obesity has been a major public health problem in the United States, with more than 1 in 3 adults qualifying for obesity from 2009 to 2010 [based on a body mass index (BMI) ≥30 kg/m²] Standard^[1]。 Obesity is not only a high risk factor for death, but also produces physical and mental comorbidities. In practice, obesity should be considered a disease state^[2,3]。 Non-surgical treatment can reduce the body weight of patients by 5% to 10%, and improve the health status of severely obese people. While bariatric surgery is suitable for clinically severe obese patients^[4]。 At present, bariatric surgery has been regarded as the most successful and durable treatment for obesity. In addition, while overall obesity rates and bariatric surgery have stabilized, severely obese patients continue to increase in the United States, with approximately 15 million BMI ≥40 kg/m now²The crowd of^[1,5]。 Only 1% of obese people who are suitable for surgery have undergone surgical treatment.

Chronic refractory ulcer of diabetic skin is one of the most difficult and serious complications of diabetes, and it has always been a difficult problem in wound treatment. The main clinical manifestations are local ulcer, infection and gangrene. Because of the long-lasting refractory treatment, it brings great pain and financial burden to patients. In recent years, due to the increasing incidence of diabetes, there is a trend of increasing this disease in clinic, but it is mainly caused by trauma, infection, pressure ulcer and other inducements, and the location is mainly in diabetic foot and lower limbs. There are few reports of chronic refractory skin ulcer in diabetic patients caused by chemotherapeutic drug extravasation during cancer chemotherapy. This article now reports a case of chronic refractory skin ulcer with large area of elbow skin caused by intravenous paclitaxel extravasation in type 2 diabetes mellitus and breast cancer patients.

Autoimmune hypoglycemia (AIH) is a rare cause of hypoglycemia, and its clinical features are spontaneous hypoglycemic episodes, hyperinsulinemia and positive insulin antibodies or insulin receptor antibodies. According to the different autoantibodies, they can be divided into two types: (1) Positive antibodies (IAA) against endogenous insulin appear without exogenous insulin application, which is called insulin autoimmune syndrome (IAS), which was first reported by Hirata et al. in Japan in 1970, also known as Hirata disease^[1]； (2) is positive for antibodies (IRA) against insulin receptors on the surface of target cells, called insulin resistance syndrome type B (TBIRS), which is rare^[2]Some may have hypoglycemia. After 1 case of IAS was reported in our hospital in 2009^[3]Several cases appeared one after another, and 3 more patients with IAS are now reported to improve clinical understanding.

A recent study showed that sterile mice transplanted with fat human gut bacteria gained more weight and accumulated more fat than sterile mice transplanted with lean human gut bacteria. This finding demonstrates that physical and metabolic characteristics can be transmitted through the intestinal flora, and transmissibility is determined by the diet of such rodents. This finding may mean that the research of personalized obesity therapies based on probiotics has taken another important step.

Pancreatic endocrine cells can expand rapidly through regeneration and proliferation during embryogenesis, but the rate of islet cell renewal becomes very slow in adulthood. In mouse mature pancreatic beta cells, the disruption of retinoblastoma inhibitor protein (Rb) plays a very limited role in cell proliferation. In this study, the researchers found that the loss of Rb in islet progenitor cells during embryogenesis can cause an increase in the number of neurogenin 3 (Ngn3) expressing precursor cells. Moreover, this trend can still be maintained after birth and is associated with an increase in the number of islet beta cells in adulthood. Correspondingly, Rb-deficient islet precursor cells can cause a decrease in the number of alpha cells by inhibiting cell outcome factor (ARX). It is p53 cells that play the opposite effect in Rb-deficient alpha and beta cells, which has the opposite effect in these cell types. The end result is that Rb-deleted islet precursor cells can cause a decrease in the ratio of islet alpha to beta cells, thereby improving glucose homeostasis and playing a protective role against diabetes. Cai EP, Wu X, Schroer SA, et al. Retinoblastoma tumor suppressor protein in pancreatic progenitors controls α-and β-cell fate [J]. Proc Natl Acad Sci U S A, 2013, 110: 14723-14728.

A recent study from the United States and Israel found that insulin-producing islet β cells in mice have a strong regenerative ability, suggesting that regenerative therapy can be applied in diabetic patients in principle. It is well known that physiological beta cell regeneration under stressful conditions depends on residual beta cell proliferation, but the factors that regulate and stimulate this response are not clear.

Regardless of type 1 or type 2 diabetes, it is beneficial to replenish the number of beta cells with the ability to secrete insulin. In adults, islet beta cells are mainly produced by self-replication. This study reports a mouse model of insulin resistance that significantly leads to islet beta cell proliferation and an increase in beta cell numbers. Using this model, we discovered a new hormone and named it betatrophin. This hormone is mainly expressed in the liver and fat. betatrophin expression is associated with beta cell proliferation in other insulin resistant mouse models and in pregnant mice. Transient expression of betatrophin in mouse liver significantly and specifically promotes islet beta cell proliferation, increases beta cell numbers and improves glucose tolerance. Therefore, betatrophin treatment can increase the number of endogenous insulin-secreting cells, which is expected to radiate the effect of or replace insulin injection. Yi P, Park JS, Melton DA. Betatrophin: a hormone that controls pancreatic β cell proliferation [J]. Cell, 2013, 153:747-758.

Studies have shown that the progression of type 2 diabetes is associated with a reduction in pancreatic beta cell mass, which is co-regulated by beta cell death and regeneration. Animal studies suggest that beta cell regeneration has two pathways: replication of existing cells or regeneration through progenitor cells. Regeneration of beta cells has been frequently observed in mice with impaired glucose tolerance. Therefore, Yoneda et al. studied the incidence of β cell mass and β cell regeneration, replication and apoptosis in pre-diabetes and diabetes.