Type-2 Diabetic Rats Research Articles

Formulated Chitosan Microspheres Remodelled the Altered Gut Microbiota and Liver miRNA in Diet-Induced Type-2 Diabetic Rats

Formulated Chitosan Microspheres Remodelled the Altered Gut Microbiota and Liver miRNA in Diet-Induced Type-2 Diabetic Rats

The Effect of Geranylgeraniol and Ginger on Satellite Cells Myogenic State in Type 2 Diabetic Rats

Type 2 diabetes (T2D) is associated with increased inflammation and reactive oxygen species (ROS) in muscles, leading to basal satellite cell (SC) myogenic impairment (i.e., reduction in SC pool), which is critical for maintaining skeletal muscle mass. T2D may contribute to muscle atrophy, possibly due to reductions in the SC pool. Geranylgeraniol (GGOH) and ginger can reduce inflammation and enhance SC myogenesis in damaged muscles, thereby alleviating muscle atrophy; however, their effect on basal SC myogenic state and muscle mass in T2D rats is limited. Rats consumed a control diet (CON), high-fat diet with 35 mg/kg of streptozotocin (HFD), a HFD with 800 mg/kg body weight of GGOH (GG), or a HFD with 0.75% ginger root extract (GRE). In the eighth week, their soleus muscles were analyzed for Pax7, MyoD, and MSTN gene and protein expression, SC myogenic state, and muscle cross-sectional area (CSA). The HFD group had a significantly lower number of Pax7+/MyoD− and Pax7+/MSTN+ cells, less Pax7 and MyoD gene expression, and less MyoD and MSTN protein expression, with a smaller CSA than the CON group. Compared to the GG and GRE groups, the HFD group had a significantly lower number of Pax7+/MSTN+ cells, less MyoD protein expression, and smaller CSA. The GRE group also had a significantly lower number of Pax7−/MyoD+ and greater MSTN protein expression than the HFD group. Nevertheless, the CON group had a significantly greater number of Pax7+/MyoD− than the GG and GRE groups, and a greater number of Pax7−/MyoD+ cells than the GRE group with a larger CSA than the GG group. GGOH and ginger persevered muscle CSA, possibly through increased MyoD and the ability to maintain the SC pool in T2D rats.

Anti-oxidative stress effects of ethyl acetate fraction of Diaphananthe bidens Leaf in Streptozotocin-Induced Type-2 Diabetic (T2D) Rats

Anti-oxidative stress effects of ethyl acetate fraction of Diaphananthe bidens Leaf in Streptozotocin-Induced Type-2 Diabetic (T2D) Rats

Anti-Diabetic and Insulinotropic Effects of p-Anisic Acid in High-Fat Diet and Streptozotocin Induced Type-2 Diabetic Rats.

To evaluate the antidiabetic effect of p-anisic acid (p-AA) against type 2 diabetes mellitus (T2DM). Thirty-six male rats were utilized for the study. The animals were provided with the high-fat diet (HFD) and T2DM was induced through 35 mg/kg streptozotocin (STZ). Subsequently, the animals were allocated to 6 groups and subjected to the treatments for 4 weeks followed by a 2-week observation. Three treatment groups were administered with p-AA (25 mg/kg, 50 mg/kg or 100 mg/kg). Glibenclamide (3 mg/kg) was provided to the standard control group. The normal control and disease control groups were supplied with 0.1 % carboxymethyl cellulose (CMC). Subsequently, the effects of treatment on body weight (BW), blood glucose level (BGL), glycosylated haemoglobin (HbA1c), insulin, and lipid parameters were measured and the pancreas was isolated for histopathology. A statistically significant (P-value<0.001) increase in BW was observed in the p-AA (50 mg/kg and 100 mg/kg) groups. The BGL decreased significantly (P-value<0.001) in p-AA groups. p-AA significantly (P-value<0.001) regulated the levels of HbA1c and serum insulin and lipid parameters. A notable improvement in the morphology of the pancreas was observed. Treatment with p-AA exhibited significant antidiabetic effects against STZ-HFD-induced T2DM.

Repetitive transcranial magnetic stimulation elicits weight loss and improved insulin sensitivity in type 2 diabetic rats.

Type 2 diabetes (T2D) accounts for the majority of diabetes incidences and remains a widespread global chronic disorder. Apart from early lifestyle changes, intervention options for T2D are mainly pharmaceutical. Repetitive transcranial magnetic stimulation (rTMS) has been approved by the FDA as a therapeutic intervention option for major depressive disorders, with further studies also indicating its role in energy metabolism and appetite. Considering its safe and non-invasive properties, we evaluated the effects of rTMS on systemic metabolism using T2D rats. We observed that rTMS improved glucose tolerance and insulin sensitivity in T2D rats after a 10-day exposure. Improved systemic insulin sensitivity was maintained after a 21-day treatment period, accompanied by modest yet significant weight loss. Circulating serum lipid levels, including those of cholesteryl ester, tryglyceride and ceramides, were also reduced following rTMS application. RNA-seq analyses further revealed a changed expression profile of hepatic genes that are related to sterol production and fatty acid metabolism. Altered expression of hypothalamic genes that are related to appetite regulation, neural activity and ether lipid metabolism were also implicated. In summary, our data report a positive impact of rTMS on systemic insulin sensitivity and weight management of T2D rats. The underlying mechanisms via which rTMS regulates systemic metabolic parameters partially involve lipid utilization in the periphery as well as central regulation of energy intake and lipid metabolism.

Cardioprotective effect of Perakine against myocardial ischemia-reperfusion injury of type-2 diabetic rat in Langendorff-Perfused Rat Hearts: Role of TLR4/NF-kB signalling pathway.

Myocardial ischemia-reperfusion (I/R) injury is a grave life-threatening situation, if not treated well in time. The development of natural remedies for myocardial I/R injury has witnessed dramatic growth in the last decade. Prompted by the above, in the present study, we have elucidated the pharmacological effect of Perakine (PER), an indole alkaloid in myocardial ischemia-reperfusion injury in type 2 diabetic rats. The model was established by inducing diabetes in experimental rats followed by the development of myocardial I/R injury model of isolated rat heart by the use of improved Langendorff retrograde perfusion technology. Results of the study suggest that PER significantly lowered the infarct size and infarct volume, and improvement in cardiac ability (LVSP, ±dP/dtmax, and heart rate). It also showed a significant lowering of cardiac biomarkers (CK, CK(MB), ALT, AST, and LDH) in a dose-dependent manner as compared to unprotected IR rats. The level of oxidative stress (MDA, SOD, and GSH) was also found lowered in IR rats together with a reduction in the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α). The anti-inflammatory acting of PER on IR rats is believed to be linked with the reduction of TNF-α, NF-κB, and TLR4 in both RT-qPCR and western blot analysis. Our research showed that Perakine could potentially alleviate cardiac ischemia-reperfusion injury in rats by blocking the TLR4/NF-κB signaling cascade.

Biogenic Silver Nanoparticles (AgNPs) Ameliorates Oxidative Biomarkers in Type-2 Diabetic Rats: In vitro and In vivo Report

Objective: Nanoparticles (NPs) are reliable biological tools for curative purposes through their application in nanomedicine. The present study synthesized and characterized silver nanoparticles (AgNPs) from Tetrapetra tetrapleura fruit. The investigation aims to examine the antidiabetic effect of the AgNPs using in vitro and in vivo models. Methods: Briefly, the synthesized AgNPs were confirmed by the application of ultraviolet-visible (UV-Vis) spectroscopy, and five other techniques, viz; transmission electron microscopy (TEM) techniques, Fourier transform infrared (FTIR) spectroscopy, energy dispersive X-ray spectroscopy (EDX), X-ray diffraction analysis (XRD) and scanning electron microscope (SEM). The in vitro model assay investigated the scavenging effect of AgNPS on 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion (O2ˉ), hydroxyl anion (-OH), ferric reducing antioxidant power (FRAP), and α-amylase/α-glucosidase inhibitory activity. The in vivo model involving rats-induced type-2 diabetes with streptozotocin (STZ) was divided into six (6) groups of seven (7) rats each to assess antioxidative parameters. Results: The AgNPs scavenged free radicals (DPPH) and moderately inhibited (O2ˉ), hydroxyl anion (-OH), reduced ferric to ferrous ions, and inhibited both α-amylase and α-glucosidase activity with increasing concentrations. Similarly, AgNPs ameliorated oxidative stress imposed by type 2 diabetes on the rats’ tissues significantly (p &lt; 0.05), depleting total cholesterol, low-density lipoprotein (LDL), and increased total protein composite and high-density lipoprotein (HDL) contents. The AgNPs enhanced catalase and superoxide dismutase, reduced glutathione (GSH), and, concomitantly, decreased malondialdehyde (MDA) levels in the tissue homogenate. Conclusion: These findings provide scientific evidence for the first time, finding the application of a biogenic compound synthesized from T. tetrapleura fruit in the treatment of type 2 diabetes.

Evidence for a Pro-Inflammatory State of Macrophages from Non-Obese Type-2 Diabetic Goto-Kakizaki Rats

Obesity causes insulin resistance (IR) through systemic low-grade inflammation and can lead to type 2 diabetes mellitus (T2DM). However, the mechanisms that cause IR and T2DM in non-obese individuals are unclear. The Goto-Kakizaki (GK) rat develops IR spontaneously and is a model of non-obese T2DM. These rats exhibit hyperglycemia beginning at weaning and exhibit lower body mass than control Wistar rats. Herein, we tested the hypothesis that macrophages of GK rats are permanently in a pro-inflammatory state, which may be associated with a systemic inflammation condition that mimics the pathogenesis of obesity-induced T2DM. Using eighteen-week-old GK and control Wistar rats, we investigated the proportions of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages isolated from the peritoneal cavity. Additionally, the production of inflammatory cytokines and reactive oxygen species (ROS) in cultured macrophages under basal and stimulated conditions was assessed. It was found that phorbol myristate acetate (PMA) stimulation increased GK rat macrophage ROS production 90-fold compared to basal levels. This response was also three times more pronounced than in control cells (36-fold). The production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), tended to be upregulated in cultured macrophages from GK rats under basal conditions. Macrophages from GK rats produced 1.6 times more granulocyte-macrophage colony-stimulating factor (GM-CSF), 1.5 times more monocyte chemoattractant protein-1 (MCP-1) and 3.3 times more TNF-α than control cells when stimulated with lipopolysaccharide (LPS) (p = 0.0033; p = 0.049; p = 0.002, respectively). Moreover, compared to control cells, GK rats had 60% more M1 (p = 0.0008) and 23% less M2 (p = 0.038) macrophages. This study is the first to report macrophage inflammatory reprogramming towards a pro-inflammatory state in GK rats.

Targeting endothelial KCa channels in vivo restores arterial and endothelial function in type 2 diabetic rats

ObjectiveThis study tested the hypothesis that administration of the KCa channel activator SKA-31 restores endothelium-dependent vasodilation in vivo in Type 2 Diabetic (T2D) rats. BackgroundAcute treatment of isolated resistance arteries from T2D rats and humans with SKA-31 significantly improved endothelium-dependent vasodilation. However, it is unknown whether these in situ actions translate to intact vascular beds in vivo. MethodsMale Sprague Dawley (SD) and T2D Goto-Kakizaki (GK) rats (26–32 weeks of age) were injected intraperitoneally with either drug vehicle or 10 mg/kg SKA-31. Doppler ultrasound imaging was used to record reactive hyperemia/flow-mediated dilation (FMD) in the femoral artery following release of an occlusion cuff on the distal hind limb, along with diameter changes in the left main coronary artery in response to inhaled isoflurane (2 % → 5 %). ResultsVehicle treated SD rats exhibited a robust and reversible FMD response, the magnitude and time course of which did not differ in SD rats treated with SKA-31. In contrast, only a weak FMD response was observed in vehicle-treated T2D GK rats, whereas prior SKA-31 administration restored FMD to the level observed in control SD rats. Exposure of SD rats to 5 % isoflurane caused robust coronary artery dilation, which was not altered by prior treatment with SKA-31. In T2D GK rats, 5 % isoflurane inhalation alone did not increase coronary artery diameter, however, a strong vasodilatory response was observed following SKA-31 treatment. SKA-31 administration did not modify intrinsic heart rate responses in either protocol. ConclusionsEnhancement of KCa channel activity in vivo restores endothelium-dependent vasodilation in T2D rats that exhibit peripheral endothelial dysfunction.

Abstract Tu072: O-GlcNAcylation underlies the activation of sodium-glucose cotransporter 1 in diabetic hearts

Rationale: Type-2 diabetes (T2D) greatly increases the risk for developing heart failure. Recent evidence indicates that the cardiac expression and function of the sodium-glucose cotransporter 1 (SGLT1) is elevated in disease states, including T2D, leading to structural and functional remodeling of the heart. The mechanisms underlying SGLT1 activation in the diabetic heart are currently unknown. Objective: To investigate if SGLT1 undergoes the O-linked attachment of β- N -acetylglucosamine (O-GlcNAcylation), a post-translational modification that is exacerbated in T2D, and its effect on SGLT1 activity in diabetic hearts. Methods/Results: SGLT1 co-immunoprecipitates with O-GlcNAc in heart homogenates and HL-1 cardiomyocyte lysates. Enhancing global protein O-GlcNAcylation in HL-1 cells via si-RNA-mediated silencing of O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc from proteins, resulted in increased amounts of O-GlcNAc that precipitate with SGLT1. SGLT1 function, measured as the SGLT1-mediated Na + influx, was significantly increased in HL-1 cells with silenced OGA. These data suggest that SGLT1 undergoes O-GlcNAcylation and this modification results in SGLT1 activation. Using rats that express human amylin in the pancreatic β-cells (HIP rats) as a model of late-onset T2D and their wild-type littermates as controls, we found that a larger fraction of SGLT1 co-immunoprecipitates with O-GlcNAc in hearts from T2D rats compared to controls. The SGLT1-mediated Na + influx was larger in myocytes from T2D vs . control rats. Increasing total O-GlcNAcylation with Thiamet-G in control myocytes resulted in larger Na + influx. In reverse experiments, inhibition of O-GlcNAcylation with 6-diazo-5-oxo-L-norleucine crystalline reduced SGLT1-mediated Na + uptake in myocytes from T2D rats. Inhibition of O-GlcNAcylation in T2D myocytes reduced Ca 2+ spark frequency and this effect was significantly less pronounced with SGLT1 blocked. These results suggest that O-GlcNAcylation affects myocyte Na + regulation by activating SGLT1, which contributes to myocyte Na + overload and its downstream effects on sarcoplasmic reticulum Ca 2+ leak in T2D. Conclusion: Exacerbated O-GlcNAcylation underlies SGLT1 activation in diabetic hearts. Preventing O-GlcNAcylation may limit myocyte Na + overload and the frequency of pro-arrhythmogenic Ca 2+ sparks in myocytes from T2D rats.

Chemical detection and analysis of Astragalus-Cassia twig drug pair using UHPLC-Q-TOF-MS and HPLC-UV methods

The classic Astragalus-Cassia twig drug pair has a long history of proven efficacy. However, a fewer studies on material basis of the Astragalus and Cassia twig decoction (ACD) was researched at present. The method of UPLC-Q-TOF-MS for classifying and identifying the main chemical components of ACD was established and the differences in composition between single decoction and co-decoction were compared by using HPLC-UV. The therapeutic role of ACD on type 2 diabetes (T2D) rats was investigated. Thirty-five compounds were resolved from the ACD. Fifteen compounds were deduced from the decoction of Astragalus, whereas nine compounds were identified from Cassia twig. Pairing of herbs make a significant effect on the chemical composition of herbal decoction. ACD can play a more obvious role in alleviating the symptoms of T2D rats, compared to the application of single herb.

The Evaluation of the protective roles of canagliflozin and zinc sulphate on body weight and hepatic histology in diabetic dyslipidemia

The significant increase in diabetes prevalence in the past decade has placed a considerable strain on the global healthcare system, especially in developing nations such as Pakistan. Although current therapy options effectively manage blood glucose levels, their accompanying adverse effects can hinder patient adherence. This study investigates the therapeutic properties of Canagliflozin, a SGLT-2 inhibitor, recognized for its tolerance and supplementary advantages on body weight and blood pressure, when used in combination with Zinc Sulphate. Zinc is acknowledged for its function in the regulation of hyperglycemia and dyslipidemia. The study involved the use of a type-2 diabetic rat model, induced by a high-fat diet and streptozotocin to examine the separate and combined impacts of Canagliflozin and Zinc Sulphate on the liver's histology. A total of forty-eight male Sprague-Dawley rats were separated into six groups and the treatments were delivered for eight weeks. Body weights were observed and histological evaluations of the liver were performed with the NASH-CRN scoring system. The findings exhibited a notable decrease in body weight among the diabetic-induced groups in comparison to the normal control. The combined utilization of Canagliflozin and Zinc Sulphate showed a heightened efficacy in managing diabetes related weight loss and steatosis of liver in the rat model having type-2 diabetes. This indicates a possible combined treatment strategy that should be further investigated to enhance the management of hepatic steatosis in individuals with diabetes. The study also proposes the potential for using a reduced dosage of Canagliflozin in combination with Zinc, so limiting adverse effects.

Effect of ß- Caryophyllene on Urocortin-3 expression in adipose tissue of high fat diet and fructose-induced type-2 diabetic rats

Effect of ß- Caryophyllene on Urocortin-3 expression in adipose tissue of high fat diet and fructose-induced type-2 diabetic rats

Lipidomics Study of Type 1 Diabetic Rats Using Online Phase Transition Trapping-Supercritical Fluid Extraction-Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry.

Chromatography-mass spectrometry-based lipidomics represents an essential tool for elucidating lipid dysfunction mechanisms and is extensively employed in investigating disease mechanisms and identifying biomarkers. However, the detection of low-abundance lipids in biological matrices, along with cumbersome operational procedures, complicates comprehensive lipidomic analyses, necessitating the development of highly sensitive, environmentally friendly, and automated methods. In this study, an online phase transition trapping-supercritical fluid extraction-chromatography-mass spectrometry (PTT-SFEC-MS/MS) method was developed and successfully applied to plasma lipidomics analysis in Type 1 diabetes (T1D) rats. The PTT strategy captured entire extracts at the column head by converting CO2 from a supercritical state to a gaseous state, thereby preventing peak spreading, enhancing peak shape for precise quantification, and boosting sensitivity without any sample loss. This method utilized only 5 μL of plasma and accomplished sample extraction, separation, and detection within 27 min. Ultimately, 77 differential lipids were identified, including glycerophospholipids, sphingolipids, and glycerolipids, in T1D rat plasma. The results indicated that the progression of the disease might be linked to alterations in glycerophospholipid and sphingolipid metabolism. Our findings demonstrated a green, highly efficient, and automated method for the lipidomics analysis of biological samples, providing a scientific foundation for understanding the pathogenesis and diagnosis of T1D.

Low molecular weight chitosan (∼20 kDa) exhibits in vivo anti-hyperglycemic effects through AKT/PI3K/FOXO pathway

Diabetes, a metabolic syndrome, is a leading global cause of morbidity and mortality. Dietary polysaccharide intervention besides medication, helps in diabetes through managing blood glucose levels. The present study elucidates the anti-hyperglycemic mechanism of water-soluble LMWC (∼20 kDa), the chitosan derivative, in type-1 diabetic (T1DM) male Wistar rats induced by streptozotocin (STZ, 36 mg/kg b.w.). LMWC1 (100 mg/kg b.w.) and LMWC2 (250 mg/kg b.w.) were administered orally on alternative days for 4 weeks. LMWC lowered fasting blood glucose levels and improved symptoms like polyphagia, polydipsia, polyuria, and serum insulin levels in a dose-dependent manner. It also ameliorated hyperglycemia & dyslipidemia by mitigating the levels of pro-inflammatory factors and oxidative stress levels in the pancreas and liver. Additionally, LMWC increased the activity of key proteins involved in insulin signaling in these organs through the AKT/PI3K/FOXO pathway, enhancing insulin secretion and improving glucose metabolism in T1DM rats. This contributed to improved hepatic glycogen synthesis and suppression of gluconeogenesis in T1DM rats. In summary, LMWC could be an effective antidiabetic supplement, offering insights into dietary treatment for diabetes management.

Multifunctional Dopamine-Based Hydrogel Microneedle Electrode for Continuous Ketone Sensing.

Diabetic ketoacidosis (DKA), a severe complication of type 1 diabetes (T1D), is triggered by production of large quantities of ketone bodies, requiring patients with T1D to constantly monitor their ketone levels. Here, a skin-compatible hydrogel microneedle (HMN)-continuous ketone monitoring (HMN-CKM) device is reported. The sensing mechanism relies on the catechol-quinone chemistry inherent tothe dopamine (DA) molecules that are covalently linked to the polymer structure of the HMN patch. The DA serves the dual-purpose of acting as a redox mediator for measuring the byproduct of oxidation of 3-beta-hydroxybutyrate (β-HB), the primary ketone bodies; while, also facilitating the formation of a crosslinked HMN patch. A universal approach involving pre-oxidation and detection of the generated catechol compounds is introduced to correlate the sensor response to the β-HB concentrations. It is further shown that real-time tracking of a decrease in ketone levels of T1D rat model is possible using the HMN-CKM device, in conjunction with a data-driven machine learning model that considers potential time delays.

Beneficial In Vitro Effects of Polysaccharide and Non-Polysaccharide Components of Dendrobium huoshanense on Gut Microbiota of Rats with Type 1 Diabetes as Opposed to Metformin.

The extract of Dendrobium huoshanense, a traditional Chinese medicinal and food homologous plant belonging to the family Orchidaceae, was previously reported to have hypoglycemic and antioxidant effects. In this study, the direct effects of polysaccharide (DHP) and non-polysaccharide (NDHP) components of D. huoshanense, as well as its water extract (DHWE) were compared with that of metformin (an antidiabetic drug) on the gut microbiota (collected from fecal flora) of rats with streptozotocin-induced type 1 diabetes (T1D) using an in vitro fermentation method. The results showed that DHWE, DHP, and NDHP reduced pH and increased bacterial proliferation and short-chain fatty acid (SCFA) content in fermentation broth. DHWE, DHP, NDHP and metformin promoted the production of acetic and propionic acid, acetic acid, propionic acid and butyric acid, and propionic acid, respectively. DHWE, DHP, and NDHP reduced the abundance of Proteobacteria (subdominant pathogenic bacteria) and increased the abundance of Firmicutes (dominant beneficial gut bacteria). NDHP also reduced the abundance of Bacteroidetes (beneficial and conditional pathogenic). Metformin increased the abundance of Proteobacteria and reduced the abundance of Firmicutes and Bacteroidetes. At the genus level, NDHP promoted the proliferation of Megamonas and Megasphaera and decreased harmful bacteria (e.g., Klebsiella), and DHP increased the abundance of Prevotellaceae (opportunistic and usually harmless). By contrast, metformin increased the abundance of harmful bacteria (e.g., Citrobacter) and reduced the abundance of beneficial bacteria (e.g., Oscillospira). Our study indicates that DHWE, DHP, and NDHP are potentially more beneficial than metformin on the gut microbiota of T1D rats in vitro.

Role of LRP5/6/GSK-3β/β-catenin in the differences in exenatide- and insulin-promoted T2D osteogenesis and osteomodulation.

Insulin and exenatide are two hypoglycaemic agents that exhibit different osteogenic effects. This study compared the differences between exenatide and insulin in osseointegration in a rat model of Type 2 diabetes (T2D) and explored the mechanisms promoting osteogenesis in this model of T2D. In vivo, micro-CT was used to detect differences in the peri-implant bone microstructure in vivo. Histology, dual-fluorescent labelling, immunofluorescence and immunohistochemistry were used to detect differences in tissue, cell and protein expression around the implants. In vitro, RT-PCR and western blotting were used to measure the expression of osteogenesis- and Wnt signalling-related genes and proteins in bone marrow mesenchymal stromal cells (BMSCs) from rats with T2D (TBMSCs) after PBS, insulin and exenatide treatment. RT-PCR was used to detect the expression of Wnt bypass cascade reactions under Wnt inactivation. Micro-CT and section staining showed exenatide extensively promoted peri-implant osseointegration. Both in vivo and in vitro experiments showed exenatide substantially increased the expression of osteogenesis-related and activated the LRP5/6/GSK-3β/β-catenin-related Wnt pathway. Furthermore, exenatide suppressed expression of Bmpr1a to inhibit lipogenesis and promoted expression of Btrc to suppress inflammation. Compared to insulin, exenatide significantly improved osteogenesis in T2D rats and TBMSCs. In addition to its dependence on LRP5/6/GSK-3β/β-catenin signalling for osteogenic differentiation, exenatide-mediated osteomodulation also involves inhibition of inflammation and adipogenesis by BMPR1A and β-TrCP, respectively.

Effects of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy on gut microbiota and glucose metabolism in rats with type 2 diabetes.

Bariatric and metabolic surgery often leads to significant changes in gut microbiota composition, indicating that changes in gut microbiota after bariatric and metabolic surgery might play a role in ameliorating type 2 diabetes (T2D). However, the effects of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) on gut microbiota in T2D remain unclear. To investigate the effects of SADI-S on gut microbiota and glucose metabolism in T2D rats. Nineteen T2D rats were randomly divided into the SADI-S group (n = 10) and the sham operation with pair-feeding group (sham-PF, n = 9). Fecal samples were collected to analyze the gut microbiota composition with 16S ribosomal DNA gene sequencing. The fasting blood glucose and glycated hemoglobin were measured to evaluate the effects of SADI-S on glucose metabolism. The Chao and ACE index results indicated the richness of the gut microbial community. The ACE and Chao index values were significantly lower in the SADI-S group than in the sham-PF group, indicating that indicating that species richness was significantly lower in the SADI-S group than in the sham-PF group (p < 0.05). Shannon and Simpson indices were used to estimate the species diversity of the gut microbiota. Compared with the sham-PF group, the SADI-S group showed significantly lower Shannon index and higher Simpson index values, indicating that the species diversity was significantly lower in the SADI-S group than in the sham-PF group (p < 0.05). At the genus level, SADI-S significantly changed the abundances of 33 bacteria, including the increased anti-inflammatory bacteria (Akkermansia and Bifidobacterium) and decreased pro-inflammatory bacteria (Bacteroides). SADI-S significantly decreased the fasting blood glucose and glycated hemoglobin levels. The blood glucose level of rats was positively correlated with the relative abundances of 12 bacteria, including Bacteroides, and negatively correlated with the relative abundances of seven bacteria, including Bifidobacterium. SADI-S significantly altered the gut microbiota composition of T2D rats, including the increased anti-inflammatory bacteria (Akkermansia and Bifidobacterium) and decreased pro-inflammatory bacteria (Bacteroides). The blood glucose level of rats was positively correlated with the abundances of 12 bacteria, including Bacteroides, but negatively correlated with the relative abundance of 7 bacteria, including Bifidobacterium. These alternations in gut microbiota may be the mechanism through which SADI-S improved T2D. More studies should be performed in the future to validate these effects.

Topical naltrexone increases aquaporin 5 production in the lacrimal gland and restores tear production in diabetic rats.

Diabetes mellitus is a prevalent disease that is often accompanied by ocular surface abnormalities including delayed epithelial wound healing and decreased corneal sensitivity. The impact of diabetes on the lacrimal functional unit (LFU) and the structures responsible for maintaining tear homeostasis, is not completely known. It has been shown that the Opioid Growth Factor Receptor (OGFr), and its ligand, Opioid Growth Factor (OGF), is dysregulated in the ocular surface of diabetic rats leading to overproduction of the inhibitory growth peptide OGF. The opioid antagonist naltrexone hydrochloride (NTX) blocks the OGF-OGFr pathway, and complete blockade following systemic or topical treatment with NTX restores the rate of re-epithelialization of corneal epithelial wounds, normalizes corneal sensitivity, and reverses dry eye in diabetic animal models. These effects occur rapidly and within days of initiating treatment. The present study was designed to understand mechanisms related to the fast reversal (<5 days) of dry eye by NTX in type 1 diabetes (T1D) by investigating dysregulation of the LFU. The approach involved examination of the morphology of the LFU before and after NTX treatment. Male and female adult Sprague-Dawley rats were rendered hyperglycemic with streptozotocin, and after 6 weeks rats were considered to be a T1D model. Rats received topical NTX twice daily to one eye for 10 days. During the period of treatment, tear production and corneal sensitivity were recorded. On day 11, animals were euthanized and orbital tissues including conjunctiva, eyelids, and lacrimal glands, were removed and processed for histologic examination including immunohistochemistry. Male and female T1D rats had significantly decreased tear production and corneal insensitivity, significantly decreased number and size of lacrimal gland acini, decreased expression of aquaporin-5 (AQP5) protein and decreased goblet cell size. Thus, 10 days of NTX treatment restored tear production and corneal sensitivity to normal values, increased AQP5 expression, and restored the surface area of goblet cells to normal. NTX had no effect on the number of lacrimal gland acini or the number of conjunctival goblet cells. In summary, blockade of the OGF-OGFr pathway with NTX reversed corneal and lacrimal gland complications and restored some components of tear homeostasis confirming the efficacy of topical NTX as a treatment for ocular defects in diabetes.