Groups Of Diabetic Mice Research Articles

Commiphora gileadenesis Extracts Reduce Blood Glucose Levels, HbA1c, Lipid Profile, and CD4+ and CD8+ Subsets in Type 1 Diabetic Mice

Diabetes mellitus is a major health problem that affects the general population. Commiphora gileadensis ( C gileadensis) is a small tree that grows in the Middle East. Objective: This study explored the effect of C gileadensis on blood glucose levels, lipid profile, and T lymphocytes subsets using flow cytometry. Methodology: Forty male mice were classified into four groups: negative control; diabetic nontreated; and two groups of diabetic mice treated with C gileadensis sap and acetone extract. The blood glucose levels, lipid profile, and HbA1c were estimated for each mouse in the four groups. Moreover, total lymphocytes, CD3+, CD4+, CD8+, and CD25+ subsets were estimated for all groups. Results: The blood glucose levels, triglyceride, total cholesterol, and HbA1c were significantly reduced in mice treated with C gileadensis sap and acetone extract compared with the diabetic group. Total lymphocyte and CD3+ were reduced in diabetic mice treated with C gileadensis sap and acetone extract compared with the untreated diabetic group ( P < .05). In addition, CD4+ and CD8+ subsets were decreased in the same groups compared with the untreated one ( P < .05). CD4+ CD25+ cells were decreased in all diabetic groups compared with the control group ( P < .05). CD8+ CD25+ were increased in diabetic groups treated with C gileadensis sap and acetone extract compared with the untreated diabetic group ( P < .05). Conclusion: The present study concludes that C gileadensis sap and acetone extracts reduce the blood glucose, HbA1c, and lipid profile in diabetic mice. Moreover, this herb has anti-inflammatory properties that may help in the normalization of glycemic index and prevent T1DM progression.

A Comparative Profile of Free Radicals, Endogenous Antioxidants, and Cytokines in Mouse Model of Type 1 Diabetes Mellitus

Diabetes mellitus is a metabolic disorder characterized by high blood glucose (hyperglycemia). Hyperglycemia will cause the body to undergo physiological changes such as free radical, antioxidant and inflammation alteration. This research aims to compare the profile of free radicals, endogenous antioxidants, and cytokines in mouse models of type 1 diabetes mellitus (T1DM). Mice were separated into two different groups, normal and diabetic mice groups. The normal group was a group of mice that were not induced to have diabetic conditions, while the diabetic mice group was induced to be diabetic using streptozotocin injection. Blood glucose levels were checked every three days for 14 days, while the immune response was evaluated after 14 days using flow cytometry. Data analysis was done using SPSS software with t-test analysis. This research showed that the increasing ROS represented by MDA would trigger inflammation in T1DM represented by the increasing TNF-alpha along with IFN-gamma and reducing anti-inflammatory cytokines represented by IL-10. Interestingly, SOD expression, which is an endogenous antioxidant, is also increased in the diabetic mice group, and we conclude that it is some sort of adaptive response of the diabetic mice group against the increasing ROS.

Integrated proteomics and metabolomics analysis of D-pinitol function during hippocampal damage in streptozocin-induced aging-accelerated mice.

Diabetes can cause hippocampal damage and lead to cognitive impairment. Diabetic cognitive impairment (DCI) is a chronic complication of diabetes associated with a high disability rate; however, its pathogenesis and therapeutic targets are unclear. We aimed to explore the mechanism of hippocampal damage during diabetes and evaluate the potential role of D-pinitol (DP) in protecting hippocampal tissue and improving cognitive dysfunction. DP (150 mg/kg/day) was administered intragastrically to streptozocin-induced aging-accelerated mice for 8 weeks. Hippocampal tissues were examined using tandem mass tag (TMT)-based proteomics and liquid chromatography-mass spectrometry (LC-MS)/MS-based non-targeted metabolomic analysis. Differentially expressed proteins (DEPs) and differentially regulated metabolites (DRMs) were screened for further analysis, and some DEPs were verified using western blotting. Our results showed that 329 proteins had significantly altered hippocampal expression in untreated diabetic mice (DM), which was restored to normal after DP treatment in 72 cases. In total, 207 DRMs were identified in the DM group, and the expression of 32 DRMs was restored to normal post-DP treatment. These proteins and metabolites are involved in metabolic pathways (purine metabolism, arginine and proline metabolism, and histidine metabolism), actin cytoskeleton regulation, oxidative phosphorylation, and Rap1-mediated signaling. Our study may help to better understand the mechanism of diabetic hippocampal damage and cognitive impairment and suggest a potential therapeutic target.

Troxerutin as an anti-inflammatory and anti-oxidative drug could ameliorate Type 1 diabetes complications in C57BL/6 mice

Type 1 diabetes (T1D) is a chronic autoimmune disease that even with insulin therapy, inflammatory complications will develop in the long term. 40 inbred C57BL/6 mice were randomly divided into four groups (n=10): Control group consisted of healthy mice receiving citrate buffer, Diabetic group included a group of diabetic mice, Diabetic+TX group was a group of diabetic mice treated with troxerutin (TX), and TX group was a group of healthy mice treated with TX. Two weeks after the final dose of streptozotocin (STZ), The cytokine levels were measured using ELISA in the culture supernatants of spleen cells after 72 hours. Radioimmunoassay was used to measure insulin and c-peptide levels. The fasting blood sugar (FBS) was measured by an automatic glucometer device. lymphocyte proliferation index was evaluated using MTT assay, myeloperoxidase (MPO) level was measured in serum and pathologic studies of the kidney and liver were performed. The levels of IL-1, IL-17, TNF-α and IFN-γ as well as MPO, FBS levels and proliferation index was significantly decreased in the treated diabetic group compared to the diabetic mice (p<0.05). plasma C-peptide and insulin significantly increased in treated diabetic group than in the diabetic mice (p<0.05). Histologically, in diabetic animals treated with Tx, inflammatory and degenerative processes in both kidney and liver tissues were alleviated significantly (p<0.05). According to the results, it was supported the anti-diabetic and anti-inflammatory effects of TX, however, more studies are needed to investigate the effects of TX and the dose-response relationship in this disease.

Simultaneous Administration of Berberine and Transplantation of Endometrial Stem Cell-Derived Insulin Precursor Cells on a Nanofibrous Scaffold to Treat Diabetes Mellitus in Mice.

Today, significant success has been achieved in treating diabetes with cell therapy derived from various sources of stem and progenitors. The replacement of beta cells is one of the new diabetes treatment methods. To this end, the production of pancreatic beta precursors in cell culture has created an important research field for diabetes treatment. Endometrial stem cells were isolated using an enzymatic method, and after their identity was confirmed using a flow cytometry and differentiation potential assay, the isolated cells were cultured on an electrospun PCL/CS scaffold. Endometrial cells were differentiated into insulin-producing cells (IPCs), and gene expression was analyzed using the qRT-PCR and immunofluorescence to confirm the creation of IPCs. Then, IPCs on the scaffold along with berberine were applied to 5 groups of diabetic mice, and after 6 weeks, insulin, blood glucose, and weight of the animals were measured. The findings revealed that pancreatic markers were significantly expressed in IPCs compared to control cells. In addition, when compared to the control group and scaffolds, the receiving group of IPCs on scaffolds had a significant improvement (p ≤ 0.0015), and this improvement increased with the addition of berberine (decrease in blood sugar (133 mg/dL), and an increase in weight (5/39 g) and insulin (2.29 MIU/L). Thus, tissue engineering is a promising new strategy for treating diabetes and can be used in the future for cell therapy and suitable drugs for diabetic patients.

Effect of L-serine on oxidative stress markers in the kidney of streptozotocin-induced diabetic mice.

Oxidative stress is critical in the occurrence and development of diabetes and its related complications. L-serine has recently been shown to reduce oxidative stress, the incidence of autoimmune diabetes and improve glucose homeostasis. The aim of this study was to investigate the effects of daily L-serine administration on blood glucose, renal function and oxidative stress markers in the kidney of streptozotocin-induced diabetic mice. Eighteen C57BL/6 male mice were randomly divided into three groups (n = 6 per group). Streptozotocin was used to induce diabetes and a group of diabetic mice was treated with 280mg/day of L-serine dissolved in drinking water for 4weeks. The level of blood glucose, biochemical markers of renal function (total protein, urea, creatinine and albumin) and oxidative stress markers (protein carbonyls, malondialdehyde, glutathione peroxidase, superoxide dismutase and catalase) were measured using spectrophotometry. The results indicated that L-serine significantly decreased the glucose level in diabetic mice (188.6 ± 22.69mg/dL, P = 0.02). Moreover, treatment of diabetic mice with L-serine reduced protein carbonyls (3.249 ± 0.9165nmol/mg protein, P < 0.05) and malondialdehyde levels (1.891 ± 0.7696μM/mg protein, P = 0.051). However, L-serine showed no significant effects on renal function, and a slight reduction in histopathological changes was observed in mice receiving L-serine. This study revealed that L-serine effectively ameliorates oxidative stress in kidney tissue and reduces the blood glucose concentration in diabetic mice.

Antidiabetic Effect of Noni Fruit and Moringa Leaves Extract on Blood Glucose Level, Hepatic and Pancreatic Histological Features of Diabetic Mice

One of the chronic diseases with high blood glucose levels is a characteristic of Diabetes Mellitus. Utilization of herbal ingredients needs to be developed to reduce blood sugar levels in diabetes, and one of them is by using moringa leaf extract and noni fruit. This study aimed to analyze the effect of a combination of moringa leaf extract and noni fruit on blood glucose levels and tissue cytology in diabetic mice. The study was a randomized pretest-posttest control group design using 28 male mice divided into seven groups. The data analysis showed the lowest decrease in blood glucose levels in the group of diabetic mice given noni fruit and moringa leaf extract at a dose of 150mg/20g BW/oral/day for two weeks. The results of histological examination of liver and pancreas tissue showed no tissue is damaged.

Recombinant Expression of Human IL-33 Protein and Its Effect on Skin Wound Healing in Diabetic Mice.

Chronic refractory wounds are one of the complications of diabetes mellitus that require effective therapy. The dermal-wound-healing property of IL-33 in diabetics is little understood. Therefore, this study aimed to express recombinant humanized mature IL-33 (rhmatIL-33) in Escherichia coli BL21 (DE3) and demonstrate its efficacy on dermal wounds in streptozotocin (STZ)-induced diabetic and nondiabetic mice by the dorsal incisional skin wound model. Results revealed that the rhmatIL-33 accelerated the scratch-healing of keratinocytes and fibroblasts at the cellular level. The wounds of diabetic mice (DM) showed more severe ulceration and inflammation than wild-type mice (WT), and the exogenous administration of rhmatIL-33 increased wound healing in both diabetic and wild-type mice. Compared with the up-regulation of endogenous IL-33 mRNA after injury in WT mice, the IL-33 mRNA decreased after injury in DM mice. Exogenous IL-33 administration increased the endogenous IL-33 mRNA in the DM group but decreased the IL-33 mRNA expression level of the WT group, indicating that IL-33 plays a balancing role in wound healing. IL-33 administration also elevated ILC2 cells in the wounds of diabetic and non-diabetic mice and improve the transcript levels of YM1, a marker of M2 macrophages. In conclusion, Hyperglycemia in diabetic mice inhibited the expression of IL-33 in the dermal wound. Exogenous addition of recombinant IL-33 promoted wound healing in diabetic mice by effectively increasing the level of IL-33 in wound tissue, increasing ILC2 cells, and accelerating the transformation of macrophage M1 to M2 phenotype.

Pancreatic alpha cell glucagon–liver FGF21 axis regulates beta cell regeneration in a mouse model of type 2 diabetes

Aims/hypothesisGlucagon receptor (GCGR) antagonism ameliorates hyperglycaemia and promotes beta cell regeneration in mouse models of type 2 diabetes. However, the underlying mechanisms remain unclear. The present study aimed to investigate the mechanism of beta cell regeneration induced by GCGR antagonism in mice.MethodsThe db/db mice and high-fat diet (HFD)+streptozotocin (STZ)-induced mice with type 2 diabetes were treated with antagonistic GCGR monoclonal antibody (mAb), and the metabolic variables and islet cell quantification were evaluated. Plasma cytokine array and liver RNA sequencing data were used to screen possible mediators, including fibroblast growth factor 21 (FGF21). ELISA, quantitative RT-PCR and western blot were applied to verify FGF21 change. Blockage of FGF21 signalling by FGF21-neutralising antibody (nAb) was used to clarify whether FGF21 was involved in the effects of GCGR mAb on the expression of beta cell identity-related genes under plasma-conditional culture and hepatocyte co-culture conditions. FGF21 nAb-treated db/db mice, systemic Fgf21-knockout (Fgf21−/−) diabetic mice and hepatocyte-specific Fgf21-knockout (Fgf21Hep−/−) diabetic mice were used to reveal the involvement of FGF21 in beta cell regeneration. A BrdU tracing study was used to analyse beta cell proliferation in diabetic mice treated with GCGR mAb.ResultsGCGR mAb treatment improved blood glucose control, and increased islet number (db/db 1.6±0.1 vs 0.8±0.1 per mm2, p<0.001; HFD+STZ 1.2±0.1 vs 0.5±0.1 per mm2, p<0.01) and area (db/db 2.5±0.2 vs 1.2±0.2%, p<0.001; HFD+STZ 1.0±0.1 vs 0.3±0.1%, p<0.01) in diabetic mice. The plasma cytokine array and liver RNA sequencing data showed that FGF21 levels in plasma and liver were upregulated by GCGR antagonism. The GCGR mAb induced upregulation of plasma FGF21 levels (db/db 661.5±40.0 vs 466.2±55.7 pg/ml, p<0.05; HFD+STZ 877.0±106.8 vs 445.5±54.0 pg/ml, p<0.05) and the liver levels of Fgf21 mRNA (db/db 3.2±0.5 vs 1.8±0.1, p<0.05; HFD+STZ 2.0±0.3 vs 1.0±0.2, p<0.05) and protein (db/db 2.0±0.2 vs 1.4±0.1, p<0.05; HFD+STZ 1.6±0.1 vs 1.0±0.1, p<0.01). Exposure to plasma or hepatocytes from the GCGR mAb-treated mice upregulated the mRNA levels of characteristic genes associated with beta cell identity in cultured mouse islets and a beta cell line, and blockage of FGF21 activity by an FGF21 nAb diminished this upregulation. Notably, the effects of increased beta cell number induced by GCGR mAb were attenuated in FGF21 nAb-treated db/db mice, Fgf21−/− diabetic mice and Fgf21Hep−/− diabetic mice. Moreover, GCGR mAb treatment enhanced beta cell proliferation in the two groups of diabetic mice, and this effect was weakened in Fgf21−/− and Fgf21Hep−/− mice.Conclusions/interpretationOur findings demonstrate that liver-derived FGF21 is involved in the GCGR antagonism-induced beta cell regeneration in a mouse model of type 2 diabetes.Graphical abstract

Effect of origanum vulgare extract on glucose level and some parameters of immunity in alloxane diabetic mice

It is aimed to study effects of origanum vulgare on serum glucose, blood film (total and differential white blood cells and immunoglobulin (IgG,IgM,IgA and complements C3 , C4) in alloxane-induced diabetic mice. Animals were divided into five groups of 5 animals each as follows: Non-diabetic mice (control group), non-treated alloxane diabetic mice, alloxane diabetic mice treated with origanum vulgare. Alloxan diabetic mice were injected with Origanum Vulgare extract for 1,2,3 weeks at a dosage of 0.18 g/kg body weight. The mice treated with alloxan (150 mg/kg B.W) to induce diabetic were showed increased in blood glucose level (hyperglycemia) , decreased in total and differential WBCs and immunoglobulin (IgG,IgM,IgA and complements C3 , C4) compared with control group, while the results of alloxan diabetic mice treated with origanum vulgare showed significantly (P&lt;0.05) decreased in blood glucose level , increased in total and differential WBCs and immunoglobulin (IgG,IgM,IgA and complements C3 , C4) compared with alloxan diabetic mice group with out treated.

Confidence Intervals Based on the Difference of Medians for Independent Log-Normal Distributions

In this paper, we study the inferences of the difference of medians for two independent log-normal distributions. These methods include traditional methods such as the parametric bootstrap approach, the normal approximation approach, the method of variance estimates recovery approach, and the generalized confidence interval approach. The simultaneous confidence intervals for the difference in the median for more than two independent log-normal distributions are also discussed. Our simulation studies evaluate the performances of the proposed confidence intervals in terms of coverage probabilities and average lengths. We find that the parametric bootstrap approach would be a suitable choice for smaller sample sizes for the two independent distributions and multiple independent distributions. However, the method of variance estimates recovery and normal approximation approaches are alternative competitors for constructing simultaneous confidence intervals, especially when the populations have large variance. We also include two practical applications demonstrating the use of the techniques on observed data, where one data set works for the PM2.5 mass concentrations in Bangkapi and Dindaeng in Thailand and the other data came from the study of nitrogen-bound bovine serum albumin produced by three groups of diabetic mice. Both applications show that the confidence intervals from the parametric bootstrap approach have the smallest length.

IGFBP5 antisense and short hairpin RNA (shRNA) constructs improve erectile function by inducing cavernosum angiogenesis in diabetic mice.

The incidence of diabetic erectile dysfunction (ED) is rapidly increasing, and due to the severe angiopathy caused by diabetes, current drugs are ineffective at treating ED. Insulin-like growth factor-binding protein 5 (IGFBP5) promotes cell death and induces apoptosis in various cell types. To evaluate the effectiveness of IGFBP5 knockdown in improving erectile function in diabetic mice. Diabetes was induced by injecting streptozotocin (STZ) intraperitoneally into male 8-week-old C57BL/6 mice. Eight weeks after diabetes induction, mice were divided into four groups: a nondiabetic control group and three STZ-induced diabetic mice groups, which were administered intracavernous injections of phosphate buffered saline, scrambled control shRNA, or shRNA targeting mouse IGFBP5 (shIGFBP5) lentivirus particles. Two weeks later, we measured erectile function by electrically stimulating the bilateral cavernous nerve. To mimic diabetic angiopathy, primary cavernous endothelial cells (MCECs) from healthy mice were cultured and treated with glucose. IGFBP5 expression in MCECs or cavernous tissues were significantly increased under diabetic conditions, and knockdown of IGFBP5 induced MCECs angiogenic activity under high-glucose conditions. STZ-induced diabetic mice had reduced erectile function, but shIGFBP5 treatment resulted in significant improvements (to 90% of the nondiabetic control group level). Furthermore, in diabetic mice, numbers of cavernous endothelial cells, pericytes, and neuronal cells were increased by shIGFBP5 treatment, which also increased eNOS Ser1177 phosphorylation, decreased permeability and apoptosis of cavernous endothelial cells. In addition, IGFBP5 was found to mediate the AKT, ERK, p38 signaling pathways. Knockdown of IGFBP5 improved erectile function in diabetic mice by promoting cell proliferation and reducing apoptosis and permeability. Local inhibition of IGFBP5 expression may provide a new treatment strategy for diabetic ED and other ischemic vascular or neurological diseases.

Protective Effects of Chaya against Mitochondrial and Synaptic Toxicities in the Type 2 Diabetes Mouse Model TallyHO.

The purpose of our study is to determine the protective effects of the chaya leaf against mitochondrial abnormalities and synaptic damage in the Type 2 diabetes (T2D) mouse model, TallyHO (TH). The TH mouse is a naturally occurring polygenic mouse model of diabetes that mimics many characteristics of human Type 2 diabetes. Only male TH mice develop hyperglycemia and moderate obesity. Female mice display moderate obesity but do not manifest overt diabetes. In this study, we evaluated three groups of mice over a period of 11 weeks: (1) the experimental group of TH diabetic mice fed with chaya chow; (2) a diabetic control group of TH diabetic mice fed with regular chow; and (3) a non-diabetic control group of SWR/J mice fed with regular chow. Body mass and fasting blood glucose were assessed weekly. Brain and other peripheral tissues were collected. Using qRT-PCR and immunoblotting analyses, we measured the mRNA abundance and protein levels of mitochondrial biogenesis, mitochondrial dynamics, autophagy/mitophagy, and synaptic genes. Using immunofluorescence analysis, we measured the regional immunoreactivities of mitochondrial and synaptic proteins. Using biochemical methods, we assessed mitochondrial function. We found increased body mass and fasting glucose levels in the TH diabetic mice relative to the non-diabetic control SWRJ mice. In chaya chow-fed TH diabetic mice, we found significantly reduced body mass and fasting glucose levels. Mitochondrial fission genes were increased and fusion, biogenesis, autophagy/mitophagy, and synaptic genes were reduced in the TH mice; however, in the chaya chow-fed TH diabetic mice, mitochondrial fission genes were reduced and fusion, biogenesis, autophagy/mitophagy, and synaptic genes were increased. Mitochondrial function was defective in the diabetic TH mice; however, it was rescued in the chaya chow-fed TH mice. These observations strongly suggest that chaya chow reduces the diabetic properties, mitochondrial abnormalities, and synaptic pathology in diabetic, TH male mice. Our data strongly indicates that chaya can be used as natural supplemental diet for prediabetic and diabetic subjects and individuals with metabolic disorders.

Potential Protective Effect of Empagliflozin on αKlotho/ Autophagy Protein LC3 in Diabetic Retinopathy: Evidence from Diabetic Mice Model

Introduction: To study the protective efficacy of Empagliflozin (EMPA), a novel sodium glucose transporter inhibitor antidiabetic drug, on the expression of α-klotho (αKL) protein and of the autophagy key proteins Light chain 3 (LC3) in type 2 diabetic mellitus (T2DM) mice diabetic retinopathy (DR). Materials and Methods: We used the BTBR mouse strain with the ob/ob leptin-deficiency mutation that develops spontaneously severe T2DM, C57/BL mice used as control. EMPA was administrated to the diabetic mice via drinking water for a period of 12 weeks. At the end of the experiment, mice retinas were removed and subjected to further histological analysis: Immunohistochemistry and Immunofluorescence staining for αKL, LC3, protein expression level. Results: Retinal αKL protein expression levels were lower in diabetic mice than control (11.94±4.6 vs 48.4±5.33) % ** P&lt; 0.01), which were restored to near normal with EMPA treatment compared to DM mice (35+20.4% vs 11.94±4.6%,*P&lt;0.05). LC3 levels were increased in diabetic retinas compared to control (29.44±2.84 vs 15.6± 2.23) %, *** P&lt;0.01, and increased with EMPA treatment compared to control (24.77±1.4% vs, 15.6±2.3% *P&lt;0.05). There were no significant changes in ATG5 protein expression in the two groups of diabetic mice with or without EMPA. Conclusions: The data suggested that αKL protein and the autophagy proteins LC3 &amp; ATG5 are involved in the pathogenesis of DR. Our data suggested that αKL and the autophagy key protein LC3 modulators could probably be potential protective factors against retinopathy develops in T2DM patients.

Antidiabetic Activity of Extract and Fractions of Castanopsis costata Leaves on Alloxan-induced Diabetic Mice

Background: In North Sumatra, Castanopsis costata is commonly used by traditional practitioners for the treatment of diabetes mellitus, however, no studies have been carried out to substantiate this practice. Therefore, this study aims to evaluate the anti-diabetic activity of extract and fractions of C. costata leaves in mice with alloxan-induced diabetes. Methods: Swiss albino mice with alloxan-induced diabetes, were acquired and subjected to the experimental evaluations. Subsequently, the fasting blood glucose levels of the diabetic mice groups treated with glibenclamid, extract and fractions, as well as the untreated group, were evaluated after two weeks of therapy. Results: Based on the results, the ethanolic extract of C. costata considerably reduced the mice’s blood glucose levels in a dose-dependent manner, at dosages of 25, 50, 100, and 200 mg/kgBW (% DBGL: 21.10%, 46.36%, 58.94%, and 60.93%, respectively). In addition, the water fraction of C. costata leaves produced a greater reduction in blood glucose levels (% DBGL: 78.93%), compared to the ethyl acetate and n-hexane fractions (% DBGL: 67.06% and 58.83%), respectively. Meanwhile, treatment with the antidiabetic drug, glibenclamide (5 mg/kgBW) produced a 50.75% reduction in blood glucose levels. Conclusion: Based on the findings, the extract and fractions of C. costata leaves were concluded to exhibit significant anti-diabetic activity. This supported the claim that traditional practitioners in North Sumatra use the plant extract for diabetes treatment.

Phytoremedial effect of fruit extract of Moringa oleifera on alloxan induced diabetic model in Swiss albino mice

Diabetes is a metabolic disorder and global health issue. It arises because of an absolute or relative insulin deficiency that causes hyperglycemia. The study aimed to assess the antihyperglycemic, hepatoprotective, and renal protective effects of ethanolic fruit extract of Moringa oleifera, on alloxan-induced diabetic mice. Four mice were assigned to each group. Alloxan was injected at the dose of 10mg/kg/body weight intraperitoneally to make the diabetic model in mice. Control and diabetic control mice received drinking water as a placebo, while the diabetic model mice group was administered with ethanolic extract of moringa fruit at the dose of 150mg/kg/bodyweight for 12 weeks. After that, animals were sacrificed, and their blood and tissue samples were collected for biochemical and histopathological examination. The glucose level markedly (p&lt;0.0001) increased many folds in Group I (80.73± 1.24 to 221.5±13.4) and Group II (80.73 ± 1.24 from to 221.9±6.88). The level of insulin markedly (P&lt; 0.0001) decreased in both groups (6.8±0.42 to1.378±0.19) and (6.8±0.42 to1.138±0.08) respectively. Serum hepatic and renal marker enzymes increased in the diabetic group of mice. Glucose level was meaningfully (p&lt;0.0001) decreased in the M. oleifera administered group while serum insulin level significantly (p&lt;0.0001) increased. The level of liver marker enzyme and renal marker also decreased as compared to the diabetic control group. Histopathological study revealed that alloxan treatment caused damage to the liver, kidney, and pancreatic tissues while the M. oleifera administered group exhibited significant improvement in the architecture of the liver, kidney, and pancreas. Hence, M. oleifera has great potential to rejuvenate the damaged tissue and consequently can restore all the serum enzymatic and hormonal parameters.

Evaluation of Antidiabetic Activity of Sargassum tenerrimum in Streptozotocin-Induced Diabetic Mice

Diabetes mellitus has become the most predominant disease in most of the developing and developed countries. Diabetes could occur at any stage of life for which a change in sedentary life style is the possible solution. Despite the introduction of several medications, to curtail the side effects associated with diabetes mellitus, there is no medication or treatment for complete cure. Existing medications and treatments are targeted to mitigate the intensity of the disease which abruptly could result in organ failure. Rather than the available types of treatments, natural medication is reported to produce commendable results. Extracts of many medicinal plants and seaweeds have been documented to possess anti-diabetic properties. A brown alga, S. tenerrimum, found on the west coast of India, is chosen in this study to analyse the anti-diabetic property of its methanolic extract. This extract was used to treat streptozotocin-induced diabetic mice. An experimental design was framed based on acute toxicity studies to determine the change in blood glucose level, body weight, lipid profile, liver enzymes (SGPT and SGOT) and the renal function markers (urea and creatinine). After 15 days of treatment, an increase in body weight and HDL cholesterol was observed while the total cholesterol, VLDL, LDL, serum triglyceride, SGOT, SGPT, creatinine and urea decreased with 250 mg/Kg.bw of S. tenerrimum methanolic extract in Streptozotocin-induced diabetic mice group. This difference is significant (p&lt;0.05) when compared with a healthy non-diabetic mice group and a treated diabetic mice group. This proves that the methanolic extract of S. tenerrimum possess anti-diabetic property. Further research could explore the active compounds that can be used in the formulation of herbal medicine for diabetes mellitus.

Phosphoproteomics analysis of diabetic cardiomyopathy in aging-accelerated mice and effects of D-pinitol.

The molecular mechanisms of diabetic cardiomyopathy (DCM) development and D-pinitol (DP) in its treatment remain unclear. The present study is to explore the underlying mechanism of DCM in an elderly diabetic mouse model and to seek the protective targets of DP by phosphoproteomics. We used streptozotocin to induce diabetes in SAMP8 and DP (150mg/kg/day) intragastrically administrated to diabetic mice for 8weeks. The heart tissues were harvested for label-free phosphoproteomic analysis from diabetic mice. Some differentially regulated phosphorylation sites were confirmed by parallel reaction monitoring. Our results showed that 612 phosphorylation sites on 454 proteins had their phosphorylation levels significantly changed in the heart of untreated diabetic mice (DM). Of these phosphorylation sites, 216 phosphorylation sites on 182 proteins were normalized after DP treatment. We analyzed the functional signaling pathways in the heart of DP treated diabetic mice (DMT), including glucagon signaling pathway, insulin signaling pathway, mitophagy, apoptosis, and longevity regulating pathway. Two consensus motifs identified were targeted by Src and epidermal growth factor receptor between DMT and DM groups. Our study might help to better understand the mechanism of DCM, provide novel targets for estimating the protective effects of DP.

Fingolimod and Diabetic Retinopathy: A Drug Repurposing Study

This study aimed to investigate the interactions between fingolimod, a sphingosine 1-phosphate receptor (S1PR) agonist, and melanocortin receptors 1 and 5 (MCR1, MCR5). In particular, we investigated the effects of fingolimod, a drug approved to treat relapsing-remitting multiple sclerosis, on retinal angiogenesis in a mouse model of diabetic retinopathy (DR). We showed, by a molecular modeling approach, that fingolimod can bind with good-predicted affinity to MC1R and MC5R. Thereafter, we investigated the fingolimod actions on retinal MC1Rs/MC5Rs in C57BL/6J mice. Diabetes was induced in C57BL/6J mice through streptozotocin injection. Diabetic and control C57BL/6J mice received fingolimod, by oral route, for 12 weeks and a monthly intravitreally injection of MC1R antagonist (AGRP), MC5R antagonist (PG20N), and the selective S1PR1 antagonist (Ex 26). Diabetic animals treated with fingolimod showed a decrease of retinal vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), compared to diabetic control group. Fingolimod co-treatment with MC1R and MC5R selective antagonists significantly (p < 0.05) increased retinal VEGFR1, VEGFR2, and VEGFA levels compared to mice treated with fingolimod alone. Diabetic animals treated with fingolimod plus Ex 26 (S1PR1 selective blocker) had VEGFR1, VEGFR2, and VEGFA levels between diabetic mice group and the group of diabetic mice treated with fingolimod alone. This vascular protective effect of fingolimod, through activation of MC1R and MC5R, was evidenced also by fluorescein angiography in mice. Finally, molecular dynamic simulations showed a strong similarity between fingolimod and the MC1R agonist BMS-470539. In conclusion, the anti-angiogenic activity exerted by fingolimod in DR seems to be mediated not only through S1P1R, but also by melanocortin receptors.

Enhanced CD4+ and CD8+ T cell infiltrate within convex hull defined pancreatic islet borders as autoimmune diabetes progresses

The notion that T cell insulitis increases as type 1 diabetes (T1D) develops is unsurprising, however, the quantitative analysis of CD4+ and CD8+ T cells within the islet mass is complex and limited with standard approaches. Optical microscopy is an important and widely used method to evaluate immune cell infiltration into pancreatic islets of Langerhans for the study of disease progression or therapeutic efficacy in murine T1D. However, the accuracy of this approach is often limited by subjective and potentially biased qualitative assessment of immune cell subsets. In addition, attempts at quantitative measurements require significant time for manual analysis and often involve sophisticated and expensive imaging software. In this study, we developed and illustrate here a streamlined analytical strategy for the rapid, automated and unbiased investigation of islet area and immune cell infiltration within (insulitis) and around (peri-insulitis) pancreatic islets. To this end, we demonstrate swift and accurate detection of islet borders by modeling cross-sectional islet areas with convex polygons (convex hulls) surrounding islet-associated insulin-producing β cell and glucagon-producing α cell fluorescent signals. To accomplish this, we used a macro produced with the freeware software ImageJ equipped with the Fiji Is Just ImageJ (FIJI) image processing package. Our image analysis procedure allows for direct quantification and statistical determination of islet area and infiltration in a reproducible manner, with location-specific data that more accurately reflect islet areas as insulitis proceeds throughout T1D. Using this approach, we quantified the islet area infiltrated with CD4+ and CD8+ T cells allowing statistical comparison between different age groups of non-obese diabetic (NOD) mice progressing towards T1D. We found significantly more CD4+ and CD8+ T cells infiltrating the convex hull-defined islet mass of 13-week-old non-diabetic and 17-week-old diabetic NOD mice compared to 4-week-old NOD mice. We also determined a significant and measurable loss of islet mass in mice that developed T1D. This approach will be helpful for the location-dependent quantitative calculation of islet mass and cellular infiltration during T1D pathogenesis and can be combined with other markers of inflammation or activation in future studies.