Maintaining Glucose Homeostasis Research Articles

Beneficial islet inflammation in health depends on pericytic TLR/MyD88 signaling.

While inflammation is beneficial for insulin secretion during homeostasis, its transformation adversely affects β-cells and contributes to diabetes. However, the regulation of islet inflammation for maintaining glucose homeostasis remains largely unknown. Here, we identified pericytes as pivotal regulators of islet immune and β-cell function in health. Islets and pancreatic pericytes express various cytokines in healthy humans and mice. To interfere with the pericytic inflammatory response, we selectively inhibited the TLR/MyD88 pathway in these cells in transgenic mice. The loss of MyD88 impaired pericytic cytokine production. Furthermore, MyD88-deficient mice exhibited skewed islet inflammation with fewer cells, an impaired macrophage phenotype, and reduced IL-1β production. This aberrant pericyte-orchestrated islet inflammation was associated with β-cell dedifferentiation and impaired glucose response. Additionally, we found that Cxcl1, a pericytic MyD88-dependent cytokine, promoted immune IL-1β production. Treatments with either Cxcl1 or IL-1β restored the mature β-cell phenotype and glucose response in transgenic mice, suggesting a potential mechanism through which pericytes and immune cells regulate glucose homeostasis. Our study revealed pericyte-orchestrated islet inflammation as a crucial element in glucose regulation, implicating this process as a potential therapeutic target for diabetes.

A nutrient responsive lipase mediates gut-brain communication to regulate insulin secretion in Drosophila

Pancreatic β cells secrete insulin in response to glucose elevation to maintain glucose homeostasis. A complex network of inter-organ communication operates to modulate insulin secretion and regulate glucose levels after a meal. Lipids obtained from diet or generated intracellularly are known to amplify glucose-stimulated insulin secretion, however, the underlying mechanisms are not completely understood. Here, we show that a Drosophila secretory lipase, Vaha (CG8093), is synthesized in the midgut and moves to the brain where it concentrates in the insulin-producing cells in a process requiring Lipid Transfer Particle, a lipoprotein originating in the fat body. In response to dietary fat, Vaha stimulates insulin-like peptide release (ILP), and Vaha deficiency results in reduced circulatory ILP and diabetic features including hyperglycemia and hyperlipidemia. Our findings suggest Vaha functions as a diacylglycerol lipase physiologically, by being a molecular link between dietary fat and lipid amplified insulin secretion in a gut-brain axis.

TA-Cloning for Diabetes Treatment: Expressing Corynebacterium Malic Enzyme Gene in E. coli.

Diabetes mellitus represents a persistent metabolic condition marked by heightened levels of blood glucose, presenting a considerable worldwide health concern, and finding targeted treatment for it is a crucial priority for global health. Gram-positive aerobic bacteria, predominantly inhabiting water and soil, are known carriers of various enzyme-encoding genetic material, which includes the malic enzyme gene that plays a role in insulin secretion. Corynebacterium glutamicum bacteria (ATCC 21799) were acquired from the Pasteur Institute and confirmed using microbiological and molecular tests, including DNA extraction. After identification, gene purification and cloning of the maeB gene were performed using the TA Cloning method. Additionally, the enhancement of enzyme expression was assessed using the expression vector pET-28a, and validation of simulation results was monitored through a real-time PCR analysis. Based on previous studies, the malic enzyme plays a pivotal role in maintaining glucose homeostasis, and increased expression of this enzyme has been associated with enhanced insulin sensitivity. However, the production of malic enzyme has encountered numerous challenges and difficulties. This study successfully isolated the malic enzyme genes via Corynebacterium glutamicum and introduced them into Escherichia coli for high-yield production. According to the results, the optimum temperature for the activity of enzymes has been identified as 39°C.

CGAS suppresses β-cell proliferation by a STING-independent but CEBPβ-dependent mechanism

Aims/hypothesiscGAS (cyclic GMP-AMP synthase) has been implicated in various cellular processes, but its role in β-cell proliferation and diabetes is not fully understood. This study investigates the impact of cGAS on β-cell proliferation, particularly in the context of diabetes. MethodsUtilizing mouse models, including cGAS and STING (stimulator of interferon genes) knockout mice, we explored the role of cGAS in β-cell function. This involved β-cell-specific cGAS knockout (cGASβKO) mice, created by breeding cGAS floxed mice with transgenic mice expressing Cre recombinase under the insulin II promoter. We analyzed cGAS expression in diabetic mouse models, evaluated the effects of cGAS deficiency on glucose tolerance, and investigated the molecular mechanisms underlying these effects through RNA sequencing. ResultscGAS expression is upregulated in the islets of diabetic mice and by high glucose treatment in MIN6 cells. Both global cGAS deficiency and β-cell-specific cGAS knockout mice lead to improved glucose tolerance by promoting β-cell mass. Interestingly, STING knockout did not affect pancreatic β-cell mass, suggesting a STING-independent mechanism for cGAS's role in β-cells. Further analyses revealed that cGAS- but not STING-deficiency leads to reduced expression of CEBPβ, a known suppressor of β-cell proliferation, concurrently with increased β-cell proliferation. Moreover, overexpression of CEBPβ reverses the upregulation of Cyclin D1 and D2 induced by cGAS deficiency, thereby regulating β-cell proliferation. These results confirm that cGAS regulation of β-cell proliferation via a CEBPβ-dependent but STING-independent mechanism. Conclusions/interpretationOur findings highlight the pivotal role of cGAS in promoting β-cell proliferation and maintaining glucose homeostasis, potentially by regulating CEBPβ expression in a STING-independent manner. This study uncovers the significance of cGAS in controlling β-cell mass and identifies a potential therapeutic target for enhancing β-cell proliferation in the treatment of diabetes.

The impact of growth hormone (GH) therapy on glucose metabolism: A narrative review mainly focused on GH-deficient (GHD) children and adolescents

Introduction: Growth hormone (GH) deficiency (GHD) in children and adolescents is traditionally managed with GH therapy, which, while effective for promoting growth, poses potential metabolic repercussions, particularly concerning glucose metabolism. This review delineates the complex interplay between GH therapy, insulin sensitivity, and glucose homeostasis. Objective: To synthesize existing literature on the effects of GH therapy on glucose metabolism, insulin secretion, and insulin sensitivity in GH-deficient pediatric populations, aiming to illuminate the nuanced metabolic consequences and to optimize therapeutic outcomes. Results: The reviewed studies illuminate a complex influence of GH therapy on metabolic parameters. While GH promotes growth and improves body composition, it may concurrently impair insulin sensitivity, elevate fasting glucose levels, and, in some cases, induce glucose intolerance. However, the dysglycemic effect during GH therapy appears to be transient and reversible on discontinuation of therapy. The counterbalancing role of insulin-like growth factor 1 (IGF-1) and its contribution to maintaining glucose homeostasis is also highlighted, illustrating a complex metabolic interplay induced by GH therapy. Discussion: The findings underscore the variability in individual metabolic responses to GH therapy. The balance between GH-induced insulin resistance and IGF-1-mediated insulin sensitivity is crucial. Monitoring and adjusting GH therapy based on glycemic response is imperative to prevent adverse metabolic outcomes. Conclusion: GH therapy in GH-deficient children and adolescents requires careful consideration of its metabolic effects. Personalized treatment strategies and vigilant monitoring of glucose metabolism are essential to optimize therapeutic outcomes and minimize the risk of metabolic complications. Further research is warranted to establish comprehensive guidelines for managing the metabolic aspects of GH therapy in this vulnerable population.

Mechano-sensor Piezo1 inhibits glucagon production in pancreatic α-cells

ObjectiveGlucagon is a critical hormone regulating glucose metabolism. It stimulates the liver to release glucose under low blood sugar conditions, thereby maintaining blood glucose stability. Excessive glucagon secretion and hyperglycemia is observed in individuals with diabetes. Precise modulation of glucagon is significant to maintain glucose homeostasis. Piezo1 is a mechanosensitive ion channel capable of converting extracellular mechanical forces into intracellular signals, thus regulating hormonal synthesis and secretion. This study aims to investigate the role of Piezo1 in regulating glucagon production in α cells. MethodsThe effects of Piezo1 on glucagon production were examined in normal- or high-fat diet fed α cell-specific Piezo1 knockout mice (Gcg-Piezo1−/−), and the murine pancreatic α cell line αTC1–6. Expression of Proglucagon was investigated by real-time PCR and western blotting. Plasma glucagon and insulin were detected by enzyme immunoassay. ResultsUnder both normal- and high-fat diet conditions, Gcg-Piezo1−/− mice exhibited increased pancreatic α cell proportion, hyperglucagonemia, impaired glucose tolerance, and activated pancreatic mTORC1 signaling. Activation of Piezo1 by its agonist Yoda1 or overexpression of Piezo1 led to decreased glucagon synthesis and suppressed mTOR signaling pathway in αTC1–6 cells. Additionally, the levels of glucagon in the medium were also reduced. Conversely, knockdown of Piezo1 produced opposite effects. ConclusionOur study uncovers the regulatory role of the Piezo1 ion channel in α cells. Piezo1 influences glucagon production by affecting mTOR signaling pathway.

Differential contributions of G protein- or arrestin subtype-mediated signalling underlie urocortin 3-induced somatostatin secretion in pancreatic δ cells.

Pancreatic islets are modulated by cross-talk among different cell types and paracrine signalling plays important roles in maintaining glucose homeostasis. Urocortin 3 (UCN3) secreted by pancreatic β cells activates the CRF2 receptor (CRF2R) and downstream pathways mediated by different G protein or arrestin subtypes in δ cells to cause somatostatin (SST) secretion, and constitutes an important feedback circuit for glucose homeostasis. Here, we used Arrb1-/-, Arrb2-/-, Gsfl/fl and Gqfl/fl knockout mice, the G11-shRNA-GFPfl/fl lentivirus, as well as functional assays and pharmacological characterization to study how the coupling of Gs, G11 and β-arrestin1 to CRF2R contributed to UCN3-induced SST secretion in pancreatic δ cells. Our study showed that CRF2R coupled to a panel of G protein and arrestin subtypes in response to UCN3 engagement. While RyR3 phosphorylation by PKA at the S156, S2706 and S4697 sites may underlie the Gs-mediated UCN3- CRF2R axis for SST secretion, the interaction of SYT1 with β-arrestin1 is also essential for efficient SST secretion downstream of CRF2R. The specific expression of the transcription factor Stat6 may contribute to G11 expression in pancreatic δ cells. Furthermore, we found that different UCN3 concentrations may have distinct effects on glucose homeostasis, and these effects may depend on different CRF2R downstream effectors. Collectively, our results provide a landscape view of signalling mediated by different G protein or arrestin subtypes downstream of paracrine UCN3- CRF2R signalling in pancreatic β-δ-cell circuits, which may facilitate the understanding of fine-tuned glucose homeostasis networks.

Infection with SARS-CoV-2 can cause pancreatic impairment

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes. Herein, we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates (NHPs) models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients. Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans. Minor and limited phenotypic and histopathological changes were observed in adult models. Systemic proteomics and metabolomics results indicated metabolic disorders, mainly enriched in insulin resistance pathways, in infected adult NHPs, along with elevated fasting C-peptide and C-peptide/glucose ratio levels. Furthermore, in elder COVID-19 NHPs, SARS-CoV-2 infection causes loss of beta (β) cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis, activation of α-SMA and aggravated fibrosis consisting of lower collagen in serum, an increase of pancreatic inflammation and stress markers, ICAM-1 and G3BP1, along with more severe glycometabolic dysfunction. In contrast, vaccination maintained glucose homeostasis by activating insulin receptor α and insulin receptor β. Overall, the cumulative risk of diabetes post-COVID-19 is closely tied to age, suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

Fungal Depsidones Stimulate AKT-Dependent Glucose Uptake in 3T3-L1 Adipocytes.

Enhanced glucose uptake in insulin-sensitive tissues is one of the therapeutic strategies to ameliorate hyperglycemia and maintain glucose homeostasis in type 2 diabetes. This study disclosed the role of fungal depsidones in glucose uptake and the underlying mechanism in 3T3-L1 adipocytes. Depsidones, including nidulin, nornidulin, and unguinol, isolated from Aspergillus unguis, stimulate glucose uptake in adipocytes. Compared to the others, nidulin exhibited an upward trend in glucose uptake. The effect of nidulin was found to be dose- and time-dependent. Nidulin also enhanced insulin- and metformin-stimulated glucose uptake. Upregulation of GLUT4 expression and AKT and AMPK phosphorylation were observed with nidulin treatment. Blockage of AKT, but not AMPK, phosphorylation was largely accompanied by diminished glucose uptake. In agreement, nidulin triggered the translocation of GLUT4 to the plasma membrane. Importantly, nidulin elevated glucose uptake associated with increased AKT phosphorylation in insulin-resistant adipocytes. Taken together, nidulin could stimulate glucose uptake mainly through AKT-dependent GLUT4 translocation, serving as a seed compound in drug discovery for type 2 diabetes.

Evaluate Cardiopulmonary markers, oxidative stress and inflammatory markers among healthy people with and without a history of type 2 diabetes

Introduction: Type 2 diabetes mellitus (T2DM) accounts for around 90% of all cases of diabetes. In T2DM, the response to insulin is diminished, and this is defined as insulin resistance. During this state, insulin is ineffective and is initially countered by an increase in insulin production to maintain glucose homeostasis, but over time, insulin production decreases, resulting in T2DM. T2DM is most commonly seen in persons older than 45 years. Still, it is increasingly seen in children, adolescents, and younger adults due to rising levels of obesity, physical inactivity, and energy-dense diets. This is a Prospective, Cross sectional, Randomization, Observational study was conducted in the Department of Biochemistry and Medicine, Index Medical College. Inclusion Criteria: Controls without family history of type 2 diabetes: Healthy subjects in the age group of 18 - 30 years of either Gender. Cases with family history of type 2 diabetes either gender age group of 18 - 30 years of Age. Individuals who are using any medicines for any health condition to restrict in performing submaximal exercise. Total cholesterol (TC) in 18-21 years in Case Group showed an increase in Mean 209.34 + 14.85 mg/dl then control group 163.26 + 23.81 mg/dl (p=0.001), also Total cholesterol (TC) in 22-25 years in Case Group showed an increase in Mean 211.29 + 16.61 mg/dl then control group 177.42 + 27.98 mg/dl (p=0.001). HDL in 18-21 years in Case Group showed a decrease in Mean 39.35 +5.56 mg/dl then control group 40.87 + 6.20 mg/dl (p=0.167), too HDL in 22-25 years in Case Group showed a decrease in Mean 40.87 +6.22 mg/dl then control group 43.97 + 6.93 mg/dl (p=0.173). Triglycerides (TGL) in 18-21 years in Case Group showed an increase in Mean 144.07 + 9.96 mg/dl then control group 123.44 + 18.87 mg/dl (p<0.0001), in addition Triglycerides (TGL) in 22-25 years in Case Group showed an increase in Mean 147.48 + 16.70 mg/dl then control group 130.08 + 20.03 mg/dl (p=0.0147). LDL in 18-21 years in Case Group showed an increase in Mean 141.60 + 16.24 mg/dl then control group 97.71 + 16.87 mg/dl (p=0.650), similar LDL in 22-25 years in Case Group showed an increase in Mean 140.92 + 18.80 mg/dl then control group 107.43 + 19.54 mg/dl (p=0.841). VLDL in 1-21 years in Case Group showed an increase in Mean 28.74 + 2.02 mg/dl then control group 24.68 + 3.77 mg/dl (p<0.0001), moreover VLDL in 22-25 years in Case Group showed an increase in Mean 29.49 + 3.34 mg/dl then control group 26.02 + 4.01 mg/dl.

Two hexokinases of the shrimp Penaeus (Litopenaeus) vannamei are differentially expressed during oxygen limited conditions

The white shrimp Penaeus (Litopenaeus) vannamei is the most cultivated shrimp worldwide. Compared to other shrimp species, it has higher resistance to adverse conditions. During hypoxia, the shrimp reduces oxygen consumption and adjusts energy metabolism via anaerobic glycolysis, among other strategies. Hexokinase (HK) is the first enzyme of glycolysis and a key regulation point. In mammals and other vertebrates, there are several tissue-specific HK isoforms with differences in expression and enzyme activity. In contrast, crustacean HKs have been relatively little studied. We studied the P. vannamei HK isoforms during hypoxia and reoxygenation. We cloned two HK1 sequences named HK1-long (1455 bp) and HK1-short (1302 bp), and one HK2 (1344 bp). In normoxia, total HK1 expression is higher in hepatopancreas, while HK2 is higher in gills. Severe hypoxia (1 mg/L of DO) after 12 h exposure and 1 h of reoxygenation increased HK1 expression in both organs, but HK2 expression changed differentially. In hepatopancreas, HK2 expression increased in 6 and 12 h of hypoxia but diminished to normoxia levels after reoxygenation. In gills, HK2 expression decreased after 12 h of hypoxia. HK activity increased in hepatopancreas after 12 h hypoxia, opposite to gills. These results indicate that shrimp HK isoforms respond to hypoxia and reoxygenation in a tissue-specific manner. Intracellular glucose levels did not change in any case, showing the shrimp ability to maintain glucose homeostasis during hypoxia.

Adaptation of Chinese perch (Siniperca chuatsi) to different levels of dietary carbohydrates

The objective of the study was to investigate the effects of dietary carbohydrate on growth performance, feed utilization, proximate compositions, and hepatic glucolipid metabolism in Chinese perch. Triplicate groups of Chinese perch (29.51 ± 0.24 g) were fed five isonitrogenous and isolipidic diets containing graded levels of carbohydrate (2.4%, 9.7%, 16.5%, 23.9%, and 30.1%) for 8 weeks. The results based on second-order polynomial regression analysis of specific growth rate (SGR) proved that Chinese perch obtained the best growth performance at the 10.93% dietary carbohydrate level. Compared to 2.4%-carbohydrate group, 9.7%-carbohydrate group exhibited the increase in daily weight gain (DWG) and protein retention ratio (PER) and the decrease in feed conversion efficiency (FCR). Moreover, 9.7%-carbohydrate group showed the increase in the mRNA levels of pfk and cs involved in aerobic oxidation pathway, the content of liver glycogen increased significantly, and no change in glucose level. Above results suggested that a part of carbohydrates may be converted into energy for growth by aerobic oxidation pathway, or converted into glycogen for storage to maintain glucose homeostasis in Chinese perch fed with moderate-carbohydrate diet. Differently, 23.9%-carbohydrate and 30.1%-carbohydrate groups showed the decrease in DWG and PER, and the increase in FCR, compared to 2.4%-carbohydrate group. Additionally, 23.9%-carbohydrate and 30.1%-carbohydrate group presented the increase in the mRNA levels of g6pca and pc involved in gluconeogenesis, which caused the increase in plasma glucose level. However, other plasma indices related to TG-metabolite and its transport (total cholesterol, and low-density lipoprotein) did not show difference, which combined with elevated fatty acid synthesis-related gene accα mRNA level resulted in excessive liver lipid deposition. Above results indicated that unregulated gluconeogenesis and invalid outward transportation of liver TG-rich metabolites may account for the glucose intolerance of Chinese perch fed with carbohydrate-rich diet. Furthermore, compared to the results from the 4th week, the expression of gk, pfk, pc, cs, and accα genes significantly increased in the 30.1%-carbohydrate group at the 8th week. Both liver and muscle exhibited a significant elevation in crude fat content, while Daily DWG experienced a noticeable decrease. These results indicated that the glucose metabolism and growth of Chinese perch in the high-carbohydrate group are influenced by the interaction of feeding duration and carbohydrate levels. And within a certain time frame, Chinese perch can tolerate a diet rich in carbohydrates.

Apolipoprotein A-IV and its derived peptide, T55−121, improve glycemic control and increase energy expenditure

Abstract It is crucial to understand the glucose control within our bodies. Bariatric/metabolic surgeries, including laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB), provide an avenue for exploring the potential key factors involved in maintaining glucose homeostasis since these surgeries have shown promising results in improving glycemic control among patients with severe type 2 diabetes (T2D). For the first time, a markedly altered population of serum proteins in patients after LSG was discovered and analyzed through proteomics. Apolipoprotein A-IV (apoA-IV) was revealed to be increased dramatically in diabetic obese patients following LSG, and a similar effect was observed in patients after RYGB surgery. Moreover, recombinant apoA-IV protein treatment was proven to enhance insulin secretion in isolated human islets. These results showed that apoA-IV may play a crucial role in glycemic control in humans, potentially through enhancing insulin secretion in human islets. ApoA-IV was further shown to enhance energy expenditure and improve glucose tolerance in diabetic rodents, through stimulating glucose-dependent insulin secretion in pancreatic β cells, partially via Gαs-coupled GPCR/cAMP (G protein-coupled receptor/cyclic adenosine monophosphate) signaling. Furthermore, T55−121, truncated peptide 55−121 of apoA-IV, was discovered to mediate the function of apoA-IV. These collective findings contribute to our understanding of the relationship between apoA-IV and glycemic control, highlighting its potential as a biomarker or therapeutic target in managing and improving glucose regulation.

Exploring the potential of pheophorbide A, a chlorophyll-derived compound in modulating GLUT for maintaining glucose homeostasis.

Pheophorbide A, a chlorophyll-breakdown product, is primarily investigated for its anti-oxidant and anti-inflammatory activity. Recent reports on pheophorbide A have shown its potential in lowering blood glucose levels, thus leading to the exploration of its use in diabetes management. Literature has also shown its effect on enhanced insulin secretion, whereas its mechanism on glucose stimulated insulin secretion (GSIS) in pancreatic β cells remains unexplored. In-silico and in-vitro investigations were used to explore the effect of pheophorbide A on class I glucose transporters (GLUTs). In-silico studies include - Molecular docking studies and stability assessment using GROMACS. In-vitro studies include - MTT assay, Glucose uptake assay, Live-cell imaging and tracking of GLUTs in presence of Pheophorbide A compared to control. Molecular docking studies revealed better binding affinity of pheophorbide A with GLUT4 (-11.2 Kcal/mol) and GLUT1 (-10.7 Kcal/mol) when compared with metformin (-5.0 Kcal/mol and -4.9 Kcal/mol, respectively). Glucose levels are largely regulated by GLUTs where GLUT1 is one of the transporters that is ubiquitously present in human β cells. Thus, we confirmed the stability of the complex, that is, pheophorbide A-GLUT1 using GROMACS for 100 ns. We further assessed its effect on a pancreatic β cell line (INS-1) for its viability using an MTT assay. Pheophorbide A (0.1-1 µM) showed a dose-dependent response on cell viability and was comparable to standard metformin. To assess how pheophorbide A mechanistically acts on GLUT1 in pancreatic β cell, we transfected INS-1 cells with GLUT1-enhanced green fluorescent protein and checked how the treatment of pheophorbide A (0.50 µM) modulates GLUT1 trafficking using live-cell imaging. We observed a significant increase in GLUT1 density when treated with pheophorbide A (0.442 ± 0.01 µm-2) at 20 mM glucose concentration when compared to GLUT1 control (0.234 ± 0.01 µm-2) and metformin (0.296 ± 0.02 µm-2). The average speed and distance travelled by GLUT1 puncta were observed to decrease when treated with pheophorbide A. The present study also demonstrated the potential of pheophorbide A to enhance glucose uptake in β cells. The current study's findings were validated by in-silico and cellular analyses, suggesting that pheophorbide A may regulate GLUT1 and might be regarded as a potential lead for boosting the GSIS pathway, thus maintaining glucose homeostasis.

Role of IL-18 in adipose tissue remodeling and metabolic dysfunction.

Proinflammatory cytokines are increased in obese adipose tissue, including inflammasome key masters. Conversely, IL-18 protects against obesity and metabolic dysfunction. We focused on the IL-18 effect in controlling adipose tissue remodeling and metabolism. We used C57BL/6 wild-type (WT) and interleukine-18 deficient (IL-18-/-) male mice fed a chow diet and samples from bariatric surgery patients. IL-18-/- mice showed increased adiposity and proinflammatory cytokine levels in adipose tissue, leading to glucose intolerance. IL-18 was widely secreted by stromal vascular fraction but not adipocytes from mice's fatty tissue. Chimeric model experiments indicated that IL-18 controls adipose tissue expansion through its presence in tissues other than bone marrow. However, IL-18 maintains glucose homeostasis when present in bone marrow cells. In humans with obesity, IL-18 expression in omental tissue was not correlated with BMI or body fat mass but negatively correlated with IRS1, GLUT-4, adiponectin, and PPARy expression. Also, the IL-18RAP receptor was negatively correlated with IL-18 expression. IL-18 signaling may control adipose tissue expansion and glucose metabolism, as its absence leads to spontaneous obesity and glucose intolerance in mice. We suggest that resistance to IL-18 signaling may be linked with worse glucose metabolism in humans with obesity.

Molecular Dynamics and Docking Investigation of Flavonol Aglycones against Sulfonylurea Receptor 1 (SUR1) for Anti–diabetic Drug Design

AbstractThe effectiveness of flavonols for the treatment of certain health conditions has highlighted their importance as an alternative to conventional therapeutic drugs. In this study, fifteen (15) flavonol aglycones (no sugar moiety) were investigated against ABC transporter sulfonylurea receptor 1 (SUR1) which regulates insulin secretion in pancreatic β‐cells to maintain glucose homeostasis. Molecular docking and molecular dynamics simulations were used to examine the molecular interactions of SUR1 with selected flavonols. The binding free energies of the ligand–receptor complexes were also investigated. Important residual interactions involving the SER595, SER599, ILE423, GLN427, ALA422, ASN426, and TRP430 amino acid residues were revealed using hydrogen bonding analysis. These residues contribute to the organization for distinct folding and selectivity at the ligand–receptor interface. Selected flavonols had reasonable binding free energies with SUR1 demonstrating their potential to be considered candidates for anti–diabetic drug design.

Conveying the pathogenesis of type 1 diabetes to the blind, low-vision and diverse needs communities through sensory stimulation.

To educate members of the blind, low-vision and diverse needs communities on the pathogenesis of the chronic autoimmune disease, type 1 diabetes, members of our team with research expertise in immune-mediated diseases, participated in the 2023 Monash Sensory Science (MSS) Exhibition. Using QR code linked audio commentary, participants were guided through tactile displays demonstrating normal insulin action in the regulation of blood glucose levels and its vital role in providing energy to tissues, followed by displays describing the various stages of the immune system's aberrant attack and the eventual complete destruction of the insulin producing beta-cells of the pancreatic islets in type 1 diabetes. These models conveyed to the participants the huge effect that this autoimmune-mediated disease has on the quality of life of affected individuals including the subsequent lifelong reliance on insulin injections to maintain glucose homeostasis. This MSS Exhibition provided a unique opportunity for our researchers to engage with under-represented members of the community and to raise awareness about such a debilitating and common autoimmune disease.

Allicin Promotes Glucose Uptake by Activating AMPK through CSE/H2S-Induced S-Sulfhydration in a Muscle-Fiber Dependent Way in Broiler Chickens.

Allicin, a product of enzymatic reaction when garlic is injured, plays an important role in maintaining glucose homeostasis in mammals. However, the effect of allicin on glucose homeostasis in the state of insulin resistance remains to be elucidated. This study investigates the effect of allicin on glucose metabolism using different muscle fibers in a chicken model. Day-old male Arbor Acres broilers are randomly divided into three groups and fed a basal diet supplemented with 0, 150, or 300mgkg-1 allicin for 42 days. Results show that allicin improves the zootechnical performance of broilers at the finishing stage. The glucose loading test (2gkg-1 body mass) indicates the regulatory role of allicin on glucose homeostasis. In vitro results demonstrate allicin increases glutathione (GSH) level and the expression of cystathionine γ lyase (CSE), leading to endogenous hydrogen sulfide (H2S) production in M. pectoralis major (PM) muscle-derived myotubes. Allicin stimulates adenosine monophosphate-activated protein kinase (AMPK) S-sulfhydration and AMPK phosphorylation to promote glucose uptake, which is suppressed in the presence of d,l-propargylglycine (PAG, a CSE inhibitor). This study demonstrates that allicin induces AMPK S-sulfhydration and AMPK phosphorylation to promote glucose uptake via the CSE/H2S system in a muscle fiber-dependent manner.

Sub-nanosized vanadate hybrid clusters maintain glucose homeostasis and restore treatment response in inflammatory disease in obese mice

Sub-nanosized vanadate hybrid clusters maintain glucose homeostasis and restore treatment response in inflammatory disease in obese mice

A comparison of the effects of green tea and cocoa on glycaemic control and insulin sensitivity in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is among the most frequent chronic diseases in virtually all countries, posing a global health threat. Therefore, Preventive interventions are critical for reducing the enormous burden of diabetes. Flavanols may assist people with metabolic disorders to maintain glucose homeostasis by inhibiting digestive enzymes and glucose transporters. Green Tea (GT) and cocoa have gotten much attention since their flavanols are high. OBJECTIVES: To investigate the effects of polyphenols from GT and cocoa (>4 weeks) on reducing the incidence of complications and improving glycaemic control and insulin sensitivity in adult patients with T2DM through outcomes Fasting Blood Glucose (FBG), Fasting Blood Insulin (FBI), Haemoglobin A1c (HbA1c) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). METHODOLOGY: An electronic research programme was applied, using different databases (including Web of Science, PubMed/Medline, Scopus, and Cochrane Reviews) to find studies that have evaluated the impact of polyphenols from GT and cocoa on reducing the incidence of complications and improving glycaemic control and insulin sensitivity in adult patients with T2DM. Articles published between 2005 and 2021 in English were selected. RESULTS: 15 and 7 studies involved 738 participants on GT (348 male/390 female). In contrast, the ones focused on cocoa had 331 participants (83 male/ 248 female) with T2DM aged 18–65 years, and a BMI range of 25–34.9 kg/m2 was identified and included in the present review. 43 and 27% of studies were low-risk bias in cocoa and GT, respectively. The results of the meta-analysis showed no significant difference in FBG levels following GT and cocoa consumption compared to the control group (SMD: –0.08; 95% CI: –0.43 to 0.28; P = 0.68 and SMD: –0.65; 95% CI, –1.40 to 0.10; P = 0.09, respectively). Also, the results showed no significant difference for GT and cocoa intervention (SMD: 0.18; 95% CI: –0.27 to 0.64; P = 0.43 and SMD: –0.80; 95% CI: –1.92 to 0.31; P = 0.16, respectively). In addition, the results of the HbA1c analysis showed no significant reduction after GT and cocoa consumption (SMD: –0.41; 95% CI: –0.85 to 0.03; P = 0.07 and SMD, –0.37; 95% CI, –0.77 to 0.04; P = 0.08, respectively). There was no evidence that GT and cocoa interventions effectively improved HOMA-IR (SMD: 0.02; 95% CI: –0.16 to 0.20; P = 0.80 and SMD, –1.65; 95% CI, –3.77 to 0.46; P = 0.13, respectively CONCLUSION: The evidence shows that the short-term administration of cocoa and GT did not significantly reduce the FBG, FBI, HbA1c, and HOMA-IR levels in adult patients with T2DM.