Islet Function Research Articles

Atf4 protects islet β-cell identity and function under acute glucose-induced stress but promotes β-cell failure in the presence of free fatty acid.

Glucolipotoxicity, caused by combined hyperglycemia and hyperlipidemia, results in β-cell failure and type 2 diabetes via cellular stress-related mechanisms. Activating transcription factor 4 (Atf4) is an essential effector of stress response. We show here that Atf4 expression in β-cells is minimally required for glucose homeostasis in juvenile and adolescent mice but it is needed for β-cell function during aging and under obesity-related metabolic stress. Henceforth, Atf4-deficient β-cells older than 2 months after birth display compromised secretory function under acute hyperglycemia. In contrast, they are resistant to acute free fatty acid-induced dysfunction and reduced production of several factors essential for β-cell identity. Atf4-deficient β-cells down-regulate genes involved in protein translation. They also upregulate several lipid metabolism or signaling genes, likely contributing to their resistance to free fatty acid-induced dysfunction. These results suggest that Atf4 activation is required for β-cell identity and function under high glucose. But Atf4 activation paradoxically induces β-cell failure in high levels of free fatty acids. Different transcriptional targets of Atf4 could be manipulated to protect β-cells from metabolic stress-induced failure.

DECORIN, a triceps-derived myokine, protects sorted β-cells and human islets against chronic inflammation associated with type 2 diabetes.

Pancreatic β-cells are susceptible to inflammation, leading to decreased insulin production/secretion and cell death. Previously, we have identified a novel triceps-derived myokine, DECORIN, which plays a pivotal role in skeletal muscle-to-pancreas interorgan communication. However, whether DECORIN can directly impact β-cell function and susceptibility to inflammation remains unexplored. The effect of DECORIN was assessed in sorted human and rat β-cell and human islets from healthy and type 2 diabetes (T2D) donors. We assessed glucose-stimulated insulin secretion (GSIS) and cytokine-mediated cell death. We then challenged sorted β-cells and human islets with inflammatory cytokines commonly associated with diabetes, such as tumor necrosis factor-α (TNF-α) alone or in combination with interleukin1-β (IL1-β) and interferon-γ (cytomix). DECORIN enhanced cell spreading and the localization of phosphorylated FAK at adhesions, promoting GSIS under basal conditions. It also increased insulin granule docking adhesion length and countered the inhibitory effects of TNF-α on adhesion and actin remodeling at the β-cell surface, resulting in preserved GSIS. DECORIN protected from cell death in sorted β-cells and islets challenged with TNF-α alone or TNF-α + cytomix. Interestingly, DECORIN increased both insulin content and secretion in human islets from T2D individuals. Additionally, DECORIN treatment reversed the impaired gene expression caused by T2D and enhanced the expression of genes essential for islet function and metabolism. Collectively, we have shown that DECORIN had a beneficial effect on human islets, protecting them from inflammation-induced cell death. In T2D islets, DECORIN restores islet function and reverses the expression of T2D-associated genes. Based on our data, we propose that DECORIN is a promising therapeutic target for diabetes-associated inflammation and diabetes itself.

Association of gestational and childhood circulating C-peptide concentrations in the hyperglycemia and adverse pregnancy outcomes follow-up study.

This study examined the association of gravida C-peptide with progeny islet function and insulin sensitivity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS). Pregnancy 3rd trimester oral glucose tolerance test (OGTT), cord blood, and offspring OGTT glucose, C-peptide and insulin at age 10-14years were analyzed for 4,121 mother-child dyads. Gravida fasting and 1-hour C-peptide concentration correlations with cord blood and childhood C-peptide, insulin, insulinogenic index and insulin sensitivity, and insulin resistance [HOMA-IR]), were assessed by multiple linear regression. Maternal covariates included age, gestational age, BMI and glucose at OGTT; child covariates included age, sex, pubertal stage, BMI z score and glucose. Gravida fasting and 1-hour OGTT C-peptide was positively correlated with cord blood C-peptide, offspring OGTT C-peptide and insulin concentrations at fasting, 30min, 1-hour and 2-hour at 10-14years of age. Maternal fasting and 1-hour C-peptide concentrations were positively correlated with the insulinogenic index and HOMA-IR but inversely correlated with insulin sensitivity. Maternal C-peptide explained more variance than maternal glucose concentrations (3.0-17.9% vs 0.2-3.5%). The correlation between gravida and offspring C-peptide suggests that without crossing the placenta, insulin may influence the offspring pancreatic beta-cell development and insulin sensitivity.

Chronic intermittent fasting impairs β cell maturation and function in adolescent mice.

Intermittent fasting (IF) is a nutritional lifestyle intervention with broad metabolic benefits, but whether the impact of IF depends on the individual's age is unclear. Here, we investigated the effects of IF on systemic metabolism and β cell function in old, middle-aged, and young mice. Short-term IF improves glucose homeostasis across all age groups without altering islet function and morphology. In contrast, while chronic IF is beneficial for adult mice, it results in impaired β cell function in the young. Using single-cell RNA sequencing (scRNA-seq), we delineate that the β cell maturation and function scores are reduced in young mice. In human islets, a similar pattern is observed in type 1 (T1D), but not type 2 (T2D), diabetes, suggesting that the impact of chronic IF in adolescence is linked to the development of β cell dysfunction. Our study suggests considering the duration of IF in younger persons, as it may worsen rather than reduce diabetes outcomes.

Long-Term Islet Graft Functional Assessments in More than 500 Patients Undergoing Total Pancreatectomy with Intraportal Islet Autotransplantation.

Total pancreatectomy and intraportal islet cell auto transplantation (TPIAT) is increasingly being offered to patients with refractory chronic pancreatitis. Understanding factors that impact islet function over time is critical. We evaluated factors associated with islet function over 12 years post TPIAT using mixed meal tolerance testing (MMTT). Insulin independence and HbA1c were assessed at each time. We compared AUC C-peptide, AUC glucose, insulin independent and HbA1c patterns over time by patient characteristics using generalized linear mixed models. 555 patients (median age 32 (IQR 17,45) years, 25% pediatric; 70% female, 41% overweight/obese) undergoing TPIAT were studied. Median islet equivalents/kg (IEQ/kg) transplanted was 3,696 (IQR 2,449, 5,494) with 26% receiving low (<2500 IEQ/kg), 43% moderate (2500-5000 IEQ/kg), and 31% high islet mass (>5000 IEQ/kg). AUC C-peptide immediately post TPIAT was lowest in those with low islet mass and remained low over time. AUC C-peptide showed a modest increase in islet function over 3-4 years in moderate/high islet mass, followed by decline (p<0.0001 for difference in post-TPIAT trajectory by group). Children have better long-term islet function particularly beyond 5 years post-TPIAT, although the difference did not reach statistical significance (p=0.0608); and overweight individuals have declining islet function long-term while those with normal/low BMI have gains in the first 3-5 years (p<0.0001). Mean hemoglobin A1c was sustained at <7% for 8 years in high islet-mass. In patients with high islet mass transplanted, islet function improves in the first several years after IAT. Islet function is sustained longer in children than in adults. Overweight/obese body habitus may be detrimental to long-term islet function, highlighting the importance of maintaining a healthy body weight for TPIAT recipients.

The Important Role of p21-Activated Kinases in Pancreatic Exocrine Function

The p21-activated kinases (PAKs) are a conserved family of serine/threonine protein kinases, which are effectors for the Rho family GTPases, namely, Rac/Cdc42. PAKs are divided into two groups: group I (PAK1–3) and group II (PAK4–6). Both groups of PAKs have been well studied in apoptosis, protein synthesis, glucose homeostasis, growth (proliferation and survival) and cytoskeletal regulation, as well as in cell motility, proliferation and cycle control. However, little is known about the role of PAKs in the secretory tissues, including in exocrine tissue, such as the exocrine pancreas (except for islet function and pancreatic cancer growth). Recent studies have provided insights supporting the importance of PAKs in exocrine pancreas. This review summarizes the recent insights into the importance of PAKs in the exocrine pancreas by reviewing their presence and activation; the ability of GI hormones/neurotransmitters/GFs/post-receptor activators to activate them; the kinetics of their activation; the participation of exocrine-tissue PAKs in activating the main growth-signaling cascade; their roles in the stimulation of enzyme secretion; finally, their roles in pancreatitis. These insights suggest that PAKs could be more important in exocrine/secretory tissues than currently appreciated and that their roles should be explored in more detail in the future.

Mechanism and therapeutic potential of hippo signaling pathway in type 2 diabetes and its complications.

Loss of pancreatic islet cell mass and function is one of the most important factors in the development of type 2 diabetes mellitus, and hyperglycemia-induced lesions in other organs are also associated with apoptosis or hyperproliferation of the corresponding tissue cells. The Hippo signaling pathway is a key signal in the regulation of cell growth, proliferation and apoptosis, which has been shown to play an important role in the regulation of diabetes mellitus and its complications. Excessive activation of the Hippo signaling pathway under high glucose conditions triggered apoptosis and decreased insulin secretion in pancreatic islet cells, while dysregulation of the Hippo signaling pathway in the cells of other organ tissues led to proliferation or apoptosis and promoted tissue fibrosis, which aggravated the progression of diabetes mellitus and its complications. This article reviews the mechanisms of Hippo signaling, its individual and reciprocal regulation in diabetic pancreatic pathology, and its emerging role in the pathophysiology of diabetic complications. Potential therapeutics for diabetes mellitus that have been shown to target the Hippo signaling pathway are also summarized to provide information for the clinical management of type 2 diabetes mellitus.

Targeting GABA signaling in type 1 diabetes and its complications- an update on the state of the art.

Type 1 diabetes (T1D) is an autoimmune disease that leads to the progressive destruction of insulin-producing β cells, resulting in lifelong insulin dependence and a range of severe complications. Beyond conventional glycemic control, innovative therapeutic strategies are needed to address the underlying disease mechanisms. Recent research has highlighted gamma-aminobutyric acid (GABA) as a promising therapeutic target for T1D due to its dual role in modulating both β cell survival and immune response within pancreatic islets. GABA signaling supports β cell regeneration, inhibits α cell hyperactivity, and promotes α-to-β cell transdifferentiation, contributing to improved islet function. Moreover, GABA's influence extends to mitigating T1D complications, including nephropathy, neuropathy, and retinopathy, as well as regulating central nervous system pathways involved in glucose metabolism. This review consolidates the latest advances in GABA-related T1D therapies, covering animal preclinical and human clinical studies and examining the therapeutic potential of GABA receptor modulation, combination therapies, and dietary interventions. Emphasis is placed on the translational potential of GABA-based approaches to enhance β cell viability and counteract autoimmune processes in T1D. Our findings underscore the therapeutic promise of GABA signaling modulation as a novel approach for T1D treatment and encourage further investigation into this pathway's role in comprehensive diabetes management.

Cisplatin exposure dysregulates insulin secretion in male and female mice.

Cancer survivors have an increased risk of developing Type 2 diabetes compared to the general population. Patients treated with cisplatin, a common chemotherapeutic agent, are more likely to develop metabolic syndrome and Type 2 diabetes than age- and sex-matched controls. Surprisingly, the impact of cisplatin on pancreatic islets has not been reported. Our study aimed to determine if mouse islet function is adversely affected by systemic (in vivo) or direct (in vitro) exposure to cisplatin. In vivo cisplatin exposure led to deficits in glucose-stimulated plasma insulin levels in both male and female mice, despite no differences in glucose tolerance. In vitro cisplatin exposure to mouse islets dysregulated insulin release and reduced oxygen consumption in a non-sex specific manner. When shifting our focus to male mouse islets, cisplatin altered the expression of genes related to insulin production, oxidative stress, and the Bcl-2 family as early as 6-hours post-exposure. Genome-wide expression analysis confirmed the pronounced downregulation of genes within the insulin secretion pathway in cisplatin-exposed mouse islets. Data from 3 human organ donors confirms that the detrimental effects of cisplatin on insulin secretion and gene expression are reproduced in human islets. Our findings indicate that cisplatin exposure causes significant defects in insulin secretion and may have lasting effects on islet health.

Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles.

In this study, we designed a nanoscale platform for sustained amino acid delivery to support transplanted pancreatic islets. The platform features mesoporous silica nanoparticles (MSNPs) loaded with glutamine (G), an essential amino acid required for islet survival and function, and coated with polydopamine (PD). We investigated various PD concentrations (0.5-2 mg/mL) and incubation times (0.5-2 h) to optimize G release, identifying that a PD concentration of 0.5 mg/mL incubated for 0.5 h yielded the best results to support islet viability and functionality ex vivo, particularly under inflammatory conditions. In syngeneic islet transplantation in STZ-diabetic mice, G alone provided only temporary benefits; however, PD-G-MSNPs significantly improved islet engraftment and function, with animals maintaining glycemic control for 30 days due to controlled G release. Our findings support the use of this nanoscale platform to provide essential nutrients like G to transplanted islets until they can establish their own blood and nutrient supply.

Shorter Digestion Times of Donor Islets Is Associated With Better Islet Graft Function After Islet Transplantation

Although islet transplantation is effective in reducing severe hypoglycemia events and controlling blood glucose in patients with type 1 diabetes, maintaining islet graft function long-term is a significant challenge. Islets from multiple donors are often needed to achieve insulin independence, and even then, islet function can decline over time when metabolic demand exceeds islet mass/insulin secretory capacity. We previously developed a method that calculated the islet graft function index (GFI) and a patient’s predicted insulin requirement (PIR) using mathematical nonlinear regression. Both PIR and GFI could be used by physicians as tools to monitor islet graft function and to guide supplementing the patient with exogenous insulin to prevent beta-cell exhaustion. This study investigates the factors relating to the islet preparation process, as well as donor and recipient characteristics, and assessed their associations with PIR and GFI after transplantation. The goal is to determine the most relevant factors that influence islet graft function after transplantation. We examined the effects of donor and recipient characteristics, and islet processing factors on posttransplanted PIR and GFI. The PIR and GFI at 3 months were calculated using patients’ baseline insulin intake, posttransplant 2-h postprandial blood glucose, and glucagon-stimulated C-peptide. Thirteen transplants that resulted in progressive decline in patients’ weekly averaged insulin intake over the initial weeks after transplant (assuming constant glucose level) with available 3-month PIR and GFI data were chosen for the investigation. Univariate analyses were performed to assess the effects of donor and recipient characteristics and islet processing factors on islet graft function as reflected by PIR and GFI. The PIR and GFI were treated as continuous response variables in separate linear regression models. Shorter digestion time of isolated donor islets were associated with lower PIR (P = 0.014) and a higher GFI (P = 0.027) after transplantation. Islet injury related to digestion enzyme exposure influenced islet function as estimated using PIR and GFI post-transplantation.

Reduction of Hepatic Fat Content by Dulaglutide for the Treatment of Diabetes Mellitus: A Two-Centre Open, Single-Arm Trial.

With the elevated level of NAFLD prevalence, the incidence of diabetes, hypertension, metabolic syndrome and other diseases is also significantly elevated. GLP-1RA can exert weight loss, glucose-lowering effects and various nonglycaemic effects. However, the relationship between quantitative reduction in hepatic fat content and improvement of pancreatic islet function by GLP-1RA is unclear. This trial was a single-arm open cohort study. A total of 38 patients with T2DM and NAFLD were enrolled in the GLP-1RA treatment group. The included patients were tested for biochemical and blood glucose levels, adiponectin and FGF21 levels, and liver fat content was measured using MRI. Measure the above indicators again after at least 3 months of GLP-1RA treatment. Divided into Q1 (average decrease of 0.37%) and Q2 (average decrease of 8.6%) groups based on the degree of reduction in liver fat content. Q2 group showed an average reduction in liver fat content of 8.6%, a decrease in glycated haemoglobin of 18.17%, a weight loss of 7.29% and an increase in fasting c-peptide release by 1.03%, 1-h and 2-h postprandial c-peptide release by 28.86% and 18.28% respectively. In contrast, Q1 group had an average reduction in liver fat content of 0.37%, a decrease in glycated haemoglobin of only 6.53%, a weight loss of 3.41%, a decrease in fasting c-peptide release by 1.91% and an increase in 1-h and 2-h postprandial c-peptide release by 19.18% and 11.66% respectively. Reduction in liver fat content effectively improves pancreatic islet function secretion, particularly postprandial c-peptide secretion, especially in the first hour after a meal. This improvement leads to a decrease in glycated haemoglobin levels and promotes better compliance with blood glucose control.

Porous starch microspheres loaded with luteolin exhibit hypoglycemic activities and alter gut microbial communities in type 2 diabetes mellitus mice.

Luteolin (LUT), a natural flavonoid known for its hypoglycemic properties, is primarily sourced from vegetables such as celery and broccoli. However, its poor stability and low bioavailability in the upper digestive tract hinder its application in the functional food industry. To address these challenges, this study employed porous starch (PS) as a carrier to develop PS microspheres loaded with luteolin (PSLUT), simulating its release in vitro. The research assessed the hypoglycemic effects of LUT in type 2 diabetes mellitus (T2DM) mice both before and after PS treatment. In vitro findings demonstrated that PS improved LUT's stability in simulated gastric fluids and enhanced its in vivo bioavailability, aligning with experimental outcomes. PSLUT administration significantly improved body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), pancreatic islet function, and other relevant indicators in T2DM mice. Moreover, PSLUT alleviated abnormal liver biochemical indicators and liver tissue injury caused by T2DM. The underlying hypoglycemic mechanism of PSLUT is thought to involve the regulation of protein kinase B (AKT-1) and glucose transporter 2 (GLUT-2). After four weeks of intervention, various PSLUT doses significantly reduced the Firmicutes to Bacteroidetes ratio at the phylum level and decreased the relative abundance of harmful bacteria at the genus level, including Acetatifactor, Candidatus-Arthromitus, and Turicibacter. This microbial shift was associated with improvements in hyperglycemia-related indicators such as FBG, the area under the curve (AUC) of OGTT, and homeostasis model assessment of insulin resistance (HOMA-IR), which are closely linked to these bacterial genera. Additionally, Lachnoclostridium, Parasutterella, Turicibacter, and Papillibacter were identified as key intestinal marker genera involved in T2DM progression through Spearman correlation analysis. In conclusion, PS enhanced LUT's hypoglycemic efficacy by modulating the transcription and protein expression levels of AKT-1 and GLUT-2, as well as the relative abundance of potential gut pathogens in T2DM mice. These results provide a theoretical foundation for advancing luteolin's application in the functional food industry and further investigating its hypoglycemic potential.

Effects of FGFR2b-ligand signaling on pancreatic branching morphogenesis and postnatal islet function.

Pancreatic development is a complex process vital for maintaining metabolic balance, requiring intricate interactions among different cell types and signaling pathways. Fibroblast growth factor receptors 2b (FGFR2b)-ligands signaling from adjacent mesenchymal cells is crucial in initiating pancreatic development and differentiating exocrine and endocrine cells through a paracrine mechanism. However, the precise critical time window that affects pancreatic development remains unclear. To explore the roles of FGFR2b-ligands and identify the narrow window of time during which FGFR2b-ligand signaling affects pancreatic development, we used an inducible mouse model to control the expression of soluble dominant-negative FGFR2b (sFGFR2b) at various stages of pancreatic development. Our findings revealed a significant effect of FGFR2b-ligand signaling on epithelial morphology, lumen formation, and pancreatic branching during primary and secondary transition stages. Additionally, sFGFR2b expression reduced the number of Pdx1+ progenitor cells and altered the pancreatic islet structure. Furthermore, we examined the effect of mutation in FGF10, an FGFR2b ligand, on embryonic pancreatic β-cell function. FGF10 null mutant embryos exhibited reduced pancreatic size and a decrease number of islet-like structure. Although neonatal mice with haploinsufficiency for FGF10 exhibited abnormal glucose tolerance test results, indicating a potential diabetes predisposition, these abnormalities normalized with age, aligning with observations in wild type mice. Our study underscores the critical role of FGFR2b-ligand signaling in pancreatic development and postnatal islet function, offering insights into potential therapeutic targets for pancreatic disorders.

Nickel Sulfate-Induced GSIS Injury in MIN6 Cells by Activating the JNK Pathway Through Oxidative Stress.

Nickel has an impact on human health, especially in the context of the new energy industries. Nickel's influence on glycemia remains controversial, and the effects and mechanisms of nickel on islet function still need further exploration. MIN6 cells were treated with different concentrations of nickel sulfate (NiSO4) (0, 75, 150, and 300µg/mL) for different durations (0, 12, 24, and 48h). The study measured cell cycle progression, apoptosis, reactive oxygen species (ROS) production, oxidative stress-related indexes (T-SOD, TBARS, 8-OHdG, and GSH), glucose-induced insulin secretion (GSIS), and the expression of JNK pathway-related proteins, pancreaticoduodenal homeobox-1 (PDX-1), glucose transporter 2 (GLUT2), and forkhead box protein O1 (FOXO1). NiSO4 damaged MIN6 cells in a time- and dose-dependent manner. NiSO4 blocked the cell cycle, induced apoptosis, and reduced insulin secretion in the GSIS experiment. NiSO4 also induced ROS production, increased oxidative stress-related indexes (TRABS and 8-OHdG), and decreased antioxidant stress-related indexes (GSH and T-SOD). In addition, NiSO4 activated the JNK pathway, upregulated FOXO1 protein expression, and inhibited PDX-1 and GLUT2 protein expression, affecting insulin release during GSIS. NiSO4 inhibited the proliferation of MIN6 cells through oxidative stress, aggravated apoptosis, caused functional impairment, upregulated the expression of FOXO1 by activating the JNK pathway, inhibited the expression of PDX-1 and GLUT2 proteins, and impaired the GSIS function of islets.

Beneficial Actions of 4-Methylumbelliferone in Type 1 Diabetes by Promoting β Cell Renewal and Inhibiting Dedifferentiation.

Background/Objectives: This study aims to investigate the effects of 4-methylumbelliferone (4-MU) on islet morphology, cell phenotype and function, and to explore possible mechanisms of β cell regeneration. Methods: The Type 1 diabetes (T1D) model was induced by continuous dose injection of streptozotocin (STZ), and mice were treated with 4-MU for 3 weeks. Plasma insulin level, islet cell phenotype and immune infiltration were determined by IPGTT, ELISA, HE and immunofluorescence. The Ins2Cre/+/Rosa26-eGFP transgenic mice model was used to detect β identity change. Primary rodent islets were incubated with 4-MU or vehicle in the presence or absence of STZ, AO/PI staining, and a scanning electron microscope (SEM), PCR and ELISA were used to evaluated islet viability, islet morphology, the specific markers of islet β cells and insulin secretion. Results: Treatment with 4-MU significantly decreased blood glucose and increased plasma insulin levels in STZ-induced diabetes. The plasma insulin level in the STZ group was 7.211 ± 2.602 ng/mL, which was significantly lower than the control group level (26.94 ± 4.300 ng/mL, p < 0.001). In contrast, the plasma insulin level in the STZ + 4-MU group was 22.29 ± 7.791 ng/mL, which was significantly higher than the STZ group (p < 0.05). The 4-MU treatment increased islet and β cells numbers and decreased α cell numbers in STZ-induced diabetes. Conclusions: Islet inflammation as indicated by insulin and CD3 was caused by infiltrates, and the β cell proliferation as indicated by insulin and Ki67 was boosted by 4-MU. β cell dedifferentiation was inhibited by 4-MU as assessed by insulin and glucagon double-positive cells and confirmed by Ins2Cre/+/Rosa26-eGFP mice. In cultured primary rodent islets, 4-MU restored islet viability, protected islet morphology, inhibited β-cell dedifferentiation, and promoted insulin secretion. The benefits of 4-MU in T1D have been proved to be associated with β cells self-replication, dedifferentiation inhibition and immune progression suppression, which help to maintain β cell mass.

Transnational economic development: Pakistani and Indian diaspora in focus

IntroductionType 2 diabetes mellitus (T2DM) often leads to elevated blood glucose levels and lipid metabolism disorder, which is generally accompanied by dysbiosis of gut microbiota and metabolic dysfunction.MethodIn this study, a mouse model of T2DM was established by feeding a high-fat/sucrose diet combined with injecting a low dose of streptozotocin. The aim of this study was to analyze the regulatory effect of Suaeda salsa extract (SSE) on T2DM and its effect on the intestinal flora of mice.ResultsThe results showed that SSE could significantly improve the body weight, fasting blood glucose (FBG), area under the curve (AUC) of the oral glucose tolerance test (OGTT), glycosylated serum protein (GSP) and islet function index. Moreover, 4-week body weight, FBG, AUC of OGTT, GSP, as well as intestinal acetic and butyric acid were significantly better in the SSE-L than in the MET group (p &amp;lt; 0.05). In addition, it was also found that the potential hypoglycemic mechanism of SSE was related to the expression of Akt serine/threonine kinase (AKT-1) and glucose transporter-2 (GLUT-2) genes. Compared with the model group, SSE intervention significantly increased the abundance of probiotics, such as Soleaferrea, Alloprevotella, Lactobacillus and Faecalibaculum, while decreasing the relative abundance of harmful bacteria, such as Phocaeicola and Bilophila. Analysis of the correlation among intestinal microbiota, short chain fatty acids (SCFAs) and the hypoglycemic index showed that Dwaynesavagella was significantly correlated with acetic, propionic and butyric acid, as well as all the diabetes-related indexes analyzed in this study.DiscussionThus, this taxon can potentially be used as a microbiological marker of type 2 diabetes. Taken together, these findings demonstrate that SSE can alleviate T2DM and its complications by improving glycemia-related indicators and modulating the structure of intestinal flora.

The Counteracting Effects of Ang II and Ang-(1-7) on the Function andGrowth of Insulin-secreting NIT-1 Cells.

China now has the highest number of diabetes in the world. Angiotensin II (Ang II) causes insulin resistance by acting on the insulin signaling pathway of peripheral target tissues. However, its effect on islet β-cells remains unclear. The possible role of Angiotensin-( 1-7) [Ang-(1-7)] as an antagonist to the effects of Ang II and in treating diabetes needs to be elucidated. To assess the effects of Ang II and Ang-(1-7) on the function and growth of islet β cell line NIT-1, which is derived from the islets of non-obese diabetic/large T-antigen (NOD/LT) mice with insulinoma. NIT-1 cells were treated with Ang II, Ang-(1-7) and their respective receptor antagonists. The impact on cell function and growth was then evaluated. Ang II significantly reduced insulin-stimulated IR-β-Tyr and Akt-Ser; while Ang-(1-7), saralasin (an Ang II receptor antagonist), and diphenyleneiodonium [DPI, a nicotinamide adenine dinucleotide phosphate oxidase (NOX) antagonist] reversed the inhibiting effect. Conversely, Ang II significantly increased insulin-stimulated intracellular H2O2 and P47 phox, while saralasin and DPI reverted the effect. Furthermore, Ang-(1-7) reduced the elevated concentrations of ROS and MDA while increasing the proliferation rate that was reduced by high glucose, all of which were reversed by A-779, an antagonist of the Mas receptor (MasR). Angiotensin II poses a negative regulatory effect on insulin signal transduction, increases oxidative stress, and may inhibit the transcription of insulin genes stimulated by insulin in NIT-1 cells. Meanwhile, angiotensin-(1-7) blocked these effects via MasR. These results corroborate the rising potential of the renin-angiotensin system (RAS) in treating diabetes.

Evaluating Continuous Glucose Monitoring after Total Pancreatectomy with or without islet autotransplatation: A Scoping Systematic Review.

The review was conducted adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. 15 studies including 147 patients (adult n = 71/paediatric n = 76) reported on CGM use post-TP (n = 42) and TPIAT (n = 105). 4 were randomized controlled trials and 10 observational studies. 6 studies evaluated CGM use in the peri-operative and 6 in the immediate post-operative period (n = 8) with variable follow-up (14 hours -20 months). CGM was used as a stand-alone device (8 studies) which allowed assessment of dynamic islet function and detection of hypoglycemia (n = 1) resulting in lower glucose levels (n = 1). 6 studies evaluated insulin pump with CGM with reduction in post-operative mean glucose (n = 4), and hypoglycaemic episodes (n = 2). There were no patient reported outcome measures (PROMs) or quality of life (QoL) measures reported. CGM can be used following TP for glucose monitoring and/or linked with insulin pump device in the peri-operative period with improved glycaemic control. However, the data are limited by short follow-up and lack of PROMs and QoL measures.

Differentiation, reduction, and proliferation of pancreatic β-cells and their regulatory factors.

The prevalence of diabetes has increased rapidly in recent years, and many types of therapeutic agents have been developed. However, the main purpose of these drugs is to lower blood glucose levels, and they are not fundamental solutions. In contrast, our research has been aimed at stimulating and inducing β-cell proliferation in vivo and replenishing β-cells. We demonstrated that pancreatic ductal cells are a source of β-cells both after birth and during regeneration after partial duct ligation: cell lineage tracing showed that 39% of growing islets and 50% of adult islets during tissue regeneration contained β-cells differentiated from duct cells. We also examined the factors contributing to β-cell depletion. Insulin and cyclin A genes are tightly regulated by transcriptional activators and repressors, and we found that imbalanced and excessive levels of repressors result in a drastic reduction of insulin and β-cell numbers, leading to severe diabetes. Thus, we searched for factors that induce β-cell proliferation in vivo. In our transgenic (Tg) mice, there was a sex difference in the progression of diabetes and sex steroid hormones were shown to contribute to this. Surprisingly, in diabetic male Tg mice, modulation of sex steroid hormones under certain conditions resulted in a marked increase of β-cells. We identified Greb1 as a factor inducing β-cell proliferation in response to a rapid elevation of E2 levels. This series of studies has demonstrated that islet cells exhibit plasticity and indicates that changes of islet cell mass and function are dynamic and recoverable.