Pathogenesis and treatment of diabetes mellitus-related erectile dysfunction: current therapies and potential challenges

Erectile dysfunction(ED)is one of the important complications of diabetes,which is very common in diabetic patients,affecting more than half of male patients,and the incidence of the disease is about 3.5 times that of the normal population.The pathogenesis of diabetic erectile dysfunction(DMED)is complex,involving nerve,vascular,endocrine,muscular and psychological aspects.At present,the therapeutic approaches of DMED include drug therapy,surgery,physical therapy and so on.This article provides a review of current research on the pathogenesis and treatment of DMED.Further elucidation of the pathogenesis of DMED and the development of new therapeutic approaches are of great significance for the prevention and treatment of DMED.

糖尿病(Diabetes Mellitus·DM)的胰岛素疗法

治疗原则依据空腹血糖水下,将不同的胰岛素单独或联合进行合理的分配,使血糖接近理想水平,控制代谢紊乱,防止或延缓并发症的出现。适应症1.绝对适应症:1)胰岛素依懒型。(Ⅰ型)2)酮症酸中毒及昏迷。3)高血糖高渗性昏迷。2.相对适应症:1)非胰岛素依赖型.

Chiglitazar and Thiazolidinedione in patients with type 2 diabetes:Which is better?

This published Meta-Analysis by Lin et al is an indirect comparison between two drugs Chiglitazar and Thiazolidinedione which are commonly used for glycemic control in type-Ⅱ diabetes mellitus.In terms of safety and efficacy,this Meta-Analysis is inconclusive.

Gene Expression Profile of Human Skeletal Muscle and Adipose Tissue of Chinese Han Patients with Type 2 Diabetes Mellitus

Objective To study the differential patterns of gene expression in skeletal muscle and adipose tissue between type 2 diabetes mellitus （T2DM） patients and healthy subjects using DNA microarray analysis, Methods T2DM patiens were divided into female group, young male group and old male group. DNA microarray analysis and quantitative real-time PCR were carried out to anaIyze the relation between gene expressions and T2DM. Results The mRNA expression of 298, 578, and 350 genes was changed in the skeletal muscle of diabetes mellitus patients compared with control subjects. The 1320, 1143, and 2847 genes were modified in adipose tissue of the three groups. Among the genes surveyed, the change of 25 and 39 gene transcripts in skeletal muscle and adipose tissue was ≥2 folds, These differentially expressed genes were classified into 15 categories according to their functions. Conclusion New genes are found and T2DM can be prevented or cured.

Association between diabetes mellitus,hypertension,hyperlipidemia,chronic viral hepatitis,and the risk of multiple myeloma:a case-control study

Objective This case-control study aimed to investigate whether diabetes mellitus(DM),hypertension,hyperlipidemia,and chronic viral hepatitis are risk factors for multiple myeloma(MM).Moreover,the clinical characteristics of MM patients with or without the abovementioned exposure factors were analyzed.Methods In total,340 MM patients and 680 patients with benign diseases who were hospitalized from January 2012 to December 2017 were classified under the case group and control group,respectively.Data about medical history of DM,hypertension,hyperlipidemia and chronic viral hepatitis were collected by reviewing medical records.Univariate and multivariate analyses were conducted to compare the history of DM,hypertension,hyperlipidemia,and viral hepatitis between the two groups.Considering DM,hypertension,hyperlipidemia,and chronic viral hepatitis as exposure factors,clinical characteristics,such as renal function and presence of fungal and other types of infections,between the exposed and nonexposed groups were analyzed.Results No significant difference was observed in the prevalence of DM,hypertension,and hyperlipidemia between the case and control groups.MM patients had a higher prevalence of chronic viral hepatitis than those with benign diseases.No significant difference was observed in the prevalence of renal dysfunction,fungal infection,and non-fungal infections in MM patients with or without DM,hypertension,and hyperlipidemia.MM patients with chronic viral hepatitis had a significantly higher prevalence of nonfungal infections during hospitalization than those without.Conclusion No significant association was noted between MM and DM,hypertension,and hyperlipidemia.Chronic viral hepatitis is correlated to a significantly higher risk of MM,and MM patients with chronic viral hepatitis were more susceptible to non-fungal infections during hospitalization.Although a non-significant trend was observed in this study,we believe that DM and hypertension might be associated with a higher risk of MM.Thus,large-scale studies must be conducted to validate the results of the current study.

Non-Diabetic Renal Disease in Patients with Type 2 Diabetes Mellitus with Proteinuria

Background: Diabetes mellitus (DM) is the leading cause of end stage renal disease (ESRD) worldwide. Although DM with proteinuria is the ultimate result of diabetic nephropathy (DN), a wide spectrum of non-diabetic renal diseases (NDRD) can occur in such patients. Objective: To observe the frequency and histological pattern of NDRD in diabetic patients with proteinuria and to explore their association with clinical and laboratory parameters. Methods: This cross-sectional study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from April 2016 to September 2017. In this study a total of 38 cases of DM with proteinuria (>1 gm/24-hour) were selected purposively. Renal biopsy was done in all patients. Based on histological findings they were categorized into two groups;Group 1 with NDRD and Group II with DN. Their clinical and laboratory parameters were analyzed and compared. Results: Among the total study subjects, 21 (55.3%) were male and 17 (44.7%) were female, mean (±SD) age 43.45 ± 9.99 years in the NDRD group and 41.57 ± 9.50 years in the DN group. Thirty one cases (81.6%) out of thirty eight had NDRD and seven (18.4%) cases had isolated DN;therefore more than two third cases had NDRD. Duration of DM was found to be significantly shorter (p = 0.004) in the NDRD group. Diabetic retinopathy was present in 12.9% cases in NDRD group vs. 57.1% cases in DN group (p = 0.025). Frequency of microscopic hematuria was significantly higher (90.3%) in NDRD patients (p = 0.002). Conclusion: The frequency of NDRD in type 2 diabetic patients other than diabetic nephropathy is relatively high. Membrano proliferative glomeru-lonephritis and membranous nephropathy are more common in NDRD. Absence of diabetic retinopathy, presence of hematuria and shorter duration of DM are markers associated with NDRD in type 2 DM, which are important indicators for renal biopsy in diabetic patients with proteinuria.

Correlation between the Polymorphism of PPARγ-2 gene and the Susceptibility of Type 2 Diabetes Mellitus in Guangxi Bama Mini-pigs

[ Objective] The research aimed to discuss the relationship between the polymorphism of PPARy.2 gene and the susceptibility of type 2 diabetes mellitus （T2DM） in Guangxi Bama mini-pigs. [ Method] 24 Guangxi Bama mini-pigs were fed with high-fat and high-sucrose diet, and partial sequences of exon 2 of PPARy-2 gene were amplified by using PCR method. In addition, the contents of fasting blood glucose and insulin （INS） in Guangxi Bama mini-pigs were determined, and the glucose tolerance test （GTT） was also carried out. [ Result] There was one SNP site （19813A/G） Jn partial sequence of exon 2 of the cloned PPAFly-2 gene, and AA （7 pigs） and AG （17 pigs） genotype were detected. The contents of fasting insulin and 60-min blood glucose in GTT in AG-genotype Guangxi Bama mini-pigs were significantly higher than those of AA genotype （ P 〈0.05）, while the incidence of T2DM in AG-genotype Guangxi Bama mini-pigs （71.4%） was obviously higher than that of AA gen- otype （5.9%）. [ Conclusion] The polymorphism of 19813A/G in exon 2 of PPARy-2 gene was related with the susceptibility of T2DM in Guangxi Bama mini-pigs.

Discovery of Novel N-Glycoside and Non-Glycoside hSGLT2 Inhibitors for the Treatment of Type 2 Diabetes Mellitus

Human sodium-glucose cotransporter 2 (hSGLT2) is a membrane protein responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule. Inhibition of hSGLT2 has been regarded as a brand new therapeutic approach for the treatment of type 2 diabetes mellitus (T2DM) due to its non-insulin related characteristics with less side effects. Current commercially available hSGLT2 inhibitors are all C-glycoside inhibitors. Previous studies have reported that N-glycoside inhibitors have better potential to serve as new drugs due to their good metabolic stability. In addition, non-glycoside inhibitors have been shown to exhibit the capability to overcome the existing problems of current glycoside inhibitors, including low tissue permeability, poor stability and short serum half-time. Here, we aimed to discover novel N-glycoside and non-glycoside hSGLT2 inhibitors by a combination of several computational approaches. A ligand-based pharmacophore model was generated, well validated and subsequently utilized as a 3D query to identify novel hSGLT2 inhibitors from National Cancer Institute (NCI) and Traditional Chinese Medicine (TCM) databases. Finally, one N-glycoside (NSC679207) and one non-glycoside (TCM_Piperenol_A) hSGLT2 inhibitors were successfully identified, which were proven to exhibit excellent binding affinities, pharmacokinetic properties and less toxicity than the commercially available hSGLT2 inhibitor, canagliflozin, via molecular docking, ADMET prediction, molecular dynamics (MD) simulations and binding free energy calculations. All together, our results strongly suggest that these two compounds have great potential to serve as novel hSGLT2 inhibitors for the treatment of T2DM and their efficacies may be further examined by a series of in vitro and/or in vivo bioassays.

The Analysis of Electroretinography of Diabetes Mellitus

Purpose: In order to get deeper understanding of Diabetic Retinopathy(DR), weanalyzed and evauated the results of the amplitude and latency of F-ERG a-wave, b-waveand the total amplitudes of oscillatory potentials(Ops).Methods: F-ERG of 105 eyes from 55 cases of DM were diagnosed by the medicaldepartment from July 1997 to July 1998. The 105 eyes were examined by ophthalmoscopeand fluorescing in angiography and divided into there groups: 22 eyes with DM withoutDR(NDR), 56 eyes with background DR(BDR)and 27 eyes with proliferate DR(PDR).In addition, 30 eyes were regard as normal control group(NCG) . We used VATA-2000type vision electrophysiological instrument and inter-national standard for clinical ERG todo measure meat and recording automatically by computer.Results: 1. The proportion of eyes number of invisible wave of a-wave, b-wave of F-ERGand Ops increased with the development of DR. 2. There were significant differences ( P＜ 0. 01 )in the latency of a-wave between NCG and BDR and statistical significance (P＜ 0. 05)between BDR and NDR. There were significant differences( P ＜ 0. 01)in theamplitude of b-wave among NCG and BDR, NCG and PDR, NDR and BDR, NDR andPDR. 3. The total amplitudes of Ops lowered with progressions of DR. There weresignificant differences(P ＜ 0.01)in tota amplitudes of Ops between NCG and NDR,NCG and BDR, NDR and BDR, statistical signficance(P ＜ 0.05) between NDR andPDR. 4. There was no correlation between each index and the duration of the disease(P ＜ 0.05).Conclusion: The amplitude of a-wave, b-wave, and total amplitudes are the targets forearly diagnosis of DR. The combined analyses of the three indexes of ERG can determinethe severity, curative effect, and prognosis of the disease.

Clinical critics in the management of diabetes mellitus

There is a global epidemic of diabetes with its prevalence expected to increase from 5.1% in 2003 to 6.3% in 2025. This increase in diabetes is occurring in all nations, however, developing nations are particularly at risk. It spares no group and affects men, women, the elderly, young and people from very racial and socio-economic background. Nevertheless, certain ethnic groups including Asians are affected more than Caucasians. Large randomized clinical trials have shown that improvement in glycaemic control, together with management of diabetes-related risk factors like blood pressure and lipid control significantly reduce the micro and macro complications in individuals with type 1 and type 2 diabetes. Patient education plays a crucial role in the prevention of diabetic fool problems. In Geneva, the rate of lower limb amputations was reduced by almost 75% after an educational intervention. People with diabetes must acquire the knowledge and skills through education to provide daily self-care in diabetes management which involves maintenance of healthy living, recognition and management of diabetes problems when they arise and taking preventive measures. Some factors include patients’ biomedical variables, the psychosocial environment, the knowledge, attitudes and beliefs of patients themselves, home careers and health care providers, healthcare systems’ accessibility and availability and even the national political context may influence these self-care behaviors.

Biodegradable polymer drug-eluting stents versus second-generation drug-eluting stents in patients with and without diabetes mellitus:a single center study

Objective It remains undetermined whether biodegradable polymer drug-eluting stents(BP-DES)are superior to second generation drugeluting stents(G2-DES)in patients with and without diabetes mellitus(DM).The study aims to evaluate the efficacy and safety of G2-DES and BP-DES in patients with and without DM in a high-volume cardiovascular center in China.

Association between the SUMO4 M55V Polymorphism and Susceptibility to Type 2 Diabetes Mellitus:A Meta-analysis

Objective The aim of this study is to determine whether the SUMO4 M55V polymorphism is associated with susceptibility to type 2 diabetes mellitus （T2DM）. Methods A meta-analysis was performed to detect the potential association of the SUMO4 M55V polymorphism and susceptibility to T2DM under dominant, recessive, co-dominant （homogeneous and heterogeneous）, and additive models. Results A total of eight articles including 10 case-control studies, with a total of 2932 cases and 2679 controls, were included in this meta-analysis. The significant association between the SUMO4 M55V polymorphism and susceptibility to T2DM was observed in the dominant model （GG ＋ GA versus AA： OR = 1.21, 95% CI = 1.05-1.40, P = 0.009）, recessive model （GG versus GA ＋ AA： OR = 1.29, 95% CI = 1.07-1.356, P = 0.010）, homozygous model （GG versus AA： OR = 1.41, 95% CI = 1.06-1.56, P = 0.001）, and additive model （G versus A： OR = 1.18, 95% CI = 1.08-1.29, P = 0.001）, and marginally significant in the heterozygous model （GA versus AA： OR = 1.16, 95% CI = 0.98-1.36, P = 0.080）. In subgroup analyses, significant associations were observed in the Chinese population under four genetic models excluding the heterozygous model, whereas no statistically significant associations were observed in the Japanese population under each of the five genetic models. Conclusion The meta-analysis demonstrated that the G allele of the SUMO4 M55V polymorphism could be a susceptible risk locus to T2DM, mainly in the Chinese population, while the association in other ethnic population needs to be further validated in studies with relatively large samples.

Study of Angiotensin Converting Enzyme Gene Polymorphism in Egyptian Type 2 Diabetes Mellitus with Diabetic Kidney Disease

Objective: Diabetic kidney disease DKD (Diabetic nephropathy DN) is considered one of the chronic micro vascular complications of diabetes mellitus and considered the commonest cause leading to chronic renal failure and chronic renal dialysis. Genetic susceptibility has been implicated in DKD. The angiotensin converting enzyme (ACE) is one of the key roles in the renin angiotensin system cascade by converting angiotensin I to angiotensin II which plays a key role in regulation of blood pressure as well as electrolytes and fluid balance. This study addressed the association of (ACE) gene polymorphisms with DN in Egyptian (T2DM) patients. Methods: Our research comprised of 75 cases of T2DM with diabetic kidney disease, 100 cases of T2DM without DKD and 94 healthy volunteers. Different genotypes of ACE gene were determined by SSP-PCR analysis. Results: Gene polymorphism of ACE (DD, ID, II) in diabetic patient with DKD is 44%, 52%, 4% respectively and for T2DM individuals without DKD is 23%, 72%, 5% respectively. (DD) had significant higher frequencies in T2DM patients with DKD compared to those without DKD (p < 0.005) and (ID) had significant higher frequencies in T2DM without DKD (p < 0.0001). These results indicated that there is an association between ACE gene polymorphisms and susceptibility of diabetic patients to be affected by diabetic kidney disease. Conclusion: From our results, we can conclude that genotype of ACE in Egypt DD is the genotype of cases diabetic kidney disease. So the presence of D allele has a significant relation with diabetic kidney disease. Our data confirm the role of ACE in its relationship with diabetic kidney disease in Egyptian type 2 diabetic patients.

A Peptidomic Analysis of the Potential Comorbidity Biomarkers for Type 2 Diabetes Mellitus and Alzheimer’s Disease

Objective: To investigate the potential comorbidity biomarkers for Type 2 Diabetes Mellitus (T2DM) and Alzheimer’s disease (AD). Methods: This is a randomized case-control study. There are three groups: 1) normal control group included 32 healthy elderly people in the hospital physical examination;2) 30 patients with T2DM group;and 3) AD group has 28 cases. On-line reversed-phase liquid chromatography separation, tandem mass spectrometry analysis and iTRAQ quantification were used for identification of peptidomic analysis, then detection of three comorbidity biomarkers might be associated with T2DM and AD by ELISA. Results: The Peptidomic Analysis of the potential comorbidity biomarkers for T2DM and the AD group includes Osteopontin (OPN), Isoform 2 of Histone H2Btype 2-F and Histone H4. These potential comorbidity biomarkers for T2DM and the AD group are significantly increased than normal control group. OPN concentrations are 1.67 (0.13 - 2.63) mmol/L in the normal control group, 3.15 (1.51 - 5.35) mmol/L in the T2DM group, and 7.66 (3.55 - 15.38) mmol/L in the AD group. Histone H4 concentrations in three groups respectively are 0.21 ± 0.036 mmol/L (normal control), 0.21 ± 0.046 mmol/L (T2DM) and 0.21 ± 0.034 mmol/L(AD). Isoforms 2 of Histone H2Btype 2-F are 1.73 (0.12 - 2.60) mmol/L, 4.71 (1.26 - 6.84) mmol/L and 9.30 (0 - 20.8) mmol/Lin three groups respectively. Conclusion: The inflammatory mechanism may lead to an increase of histone content in the urine of AD and T2DM patients. Clinical test of these potential comorbidity biomarkers Histones and Osteopontin would be the diagnosis of comorbidity AD and T2DM.

Association between Socio-Demographic Factors and Blood Sugar Levels in Type 2 Diabetes Mellitus Patients in Bangladesh

Background: The aim of the current study was to evaluate the anthropometric and demographic factors and their correlation with type 2 diabetes mellitus (T2DM) in Bangladesh. Methods: One hundred fourteen patients (70 males and 44 females) between 30 and 75 years of age from various areas of Bangladesh were screened for T2DM. Fasting blood sugar (FBS) was analyzed by using laboratory kits and spectrophotometric technique. Anthropometric and socio-demographic data were collected using a structured questionnaire. Body mass index (BMI) was calculated from weight (kg) and height (m) of the individual respondents. Physical activity was categorized based on activity during daily work. Economic condition is defined by respective family income and education level is categorized into 3 levels: illiterate, 0 - 12 years of education and graduate or above. Results: According to the current study results, half of the patients were from the middle-class family with low physical activity and their age was within the range of 30 - 45 years. The male and female ratio of the study population was 60:40. Most of the patients were found to be obese and educated. Urban populations were more prone to have DM than the rural population. Age, education, the area of residence (urban and rural), physical activity and co-morbid diseases were significantly correlated with T2DM in Bangladesh (P Conclusion: Our study shows that different socio-demographic factors have a significant correlation with T2DM in Bangladesh. Diabetes awareness, early diagnosis, patient education and life-style modification can be initiated to manage T2DM efficiently.

Initiation of Basal Insulin in Patients with Uncontrolled Type 2 Diabetes Mellitus

Type 2 diabetes mellitus is a growing health problem, characterized by insulin resistance progressing to beta cell dysfunction and insulin deficiency, most of these patients will need intensification of treatment and initiation of insulin to delay or prevent diabetic complications. Glycemic control is the most important aspect of management, and in reducing morbidity and mortality of the diseases. Control of plasma glucose in patients with diabetes can be assessed by HbA1c, FPG, PPG, but still HbA1c% remains the gold standard for assessment of glycemic control and follow up of diabetic patients. The aim of this study is to assess HbA1c% in patients on oral anti-diabetic drugs, with poor glycemic control before and after adding basal insulin, with titration of the dose of insulin depending on fasting blood sugar. 82 patients with uncontrolled type 2 diabetes (43.9% male, 56.1% female), with HbA1c more than 9%, on two types of oral diabetic medication or more, were started on basal insulin (glargine, lantus) and followed for three to six months. Overall 82 patients with type 2 diabetes mellitus were included in the study. The mean age of the study population was 58.4 years, the mean duration of the disease range was 13.4 years. All patients with HbA1c more than 9%, without organ failure, were included in the study. The mean HbA1c overall had decreased from mean of 11.15% before starting basal insulin to the mean of 8.43% within 3 to 6 month, after initiating basal insulin, this difference was significant at p < 0.001. There was no adverse effect on this medication in any of the study group. The addition of basal insulin to oral anti-diabetic medication in uncontrolled insulin-naïve type 2 diabetic patients resulted in significant improvement of glycemic control, with improved HbA1c level, without adverse effects.

Surfactin alleviated hyperglycaemia in mice with type 2 diabetes induced by a high-fat diet and streptozotocin

Type 2 diabetes mellitus(T2DM)is associated with liver dysfunction and intestinal dysbiosis.Bioactive peptides(BAPs)have been reported to ameliorate T2DM by preventing oxidative damage to the liver.Bacillus amyloliquefaciens fmb50 produces the lipopeptide surfactin with a wide range of biological activities.The effects of surfactin on T2DM,on the other hand,have not been studied.In the present study,80 mg/kg body weight surfactin supplementation lowered fasting blood glucose(FBG)levels by 21.05%and insulin resistance(IR)by 18.18%compared with those in the T2DM group,reduced inflammation,and increased antioxidant activity in mice with T2DM induced by a high-fat diet(HFD)and streptozotocin(STZ).According to further research,surfactin administration reduced Firmicutes-to-Bacteroidetes ratios while increasing Bifi dobacterium abundance by 20 times and the level of the tight junction protein Occludin by 18.38%and ZO-1 by 66.60%.Furthermore,surfactin also improved hepatic glucose metabolism by activating the adenosine monophosphate-activated protein kinase(AMPK)signalling pathway,increasing glycogen synthesis and glucose transporter 2(GLUT2)protein expression while reducing glucose-6-phosphatase(G6Pase)protein expression.In addition,the increased Bifi dobacterium abundance indirectly reduced the liver burden of the metabolic products indole,cresol and amine produced by saprophytic bacteria.All of these findings revealed that surfactin not only ameliorated HFD/STZ-induced gut dysbiosis and preserved intestinal barrier integrity but also enhanced hepatic glucose metabolism and detoxifi cation function in T2DM mice.The gut microbiota appeared to be important in controlling glucose metabolism,IR,fat accumulation,inflammation and antioxidation,according to Spearman’s correlation coeffi cients.All data indicated that surfactin alleviated hyperglycaemia in mice with T2DM induced by HFD/STZ.

Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs

Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders,and it is a rapidly growing global public health issue.It is characterized by hyperglycemia,a condition involving a high blood glucose level brought on by deficiencies in insulin secretion,decreased activity of insulin,or both.Prolonged effects of diabetes include cardiovascular problems,retinopathy,neuropathy,nephropathy,and vascular alterations in both macro-and micro-blood vessels.In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis,identifying targets,and reviewing novel treatment options and medications.Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences.The most popular in vivo studies involves the small animal models,such as rodent models,chemically induced diabetogens like streptozotocin and alloxan,and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals.Other models include virally induced models,diet/nutrition induced diabetic animals,surgically induced models or pancreatectomy models,and non-obese models.Large animals or non-rodent models like porcine(pig),canine(dog),nonhuman primate,and Zebrafish models are also outlined.The in vitro models discussed are murine and human beta-cell lines and pancreatic islets,human stem cells,and organoid cultures.The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition ofα-glucosidase activity.

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

Solute carriers(SLCs) constitute the largest superfamily of membrane transporter proteins.These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions.They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake(e.g., SLC2A4/GLUT4), glucose reabsorption(e.g., SLC5A2/SGLT2), thermogenesis(e.g., SLC25A7/UCP-1), and ATP production(e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus(T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone(SLCO1B1/OATP1B1) and metformin(SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

Mannogalactoglucan from mushrooms protects pancreatic islets via restoring UPR and promotes insulin secretion in TIDM mice

Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.