Hyperglycemia In Mouse Model Research Articles

Diminished light sensitivities of ON alpha retinal ganglion cells observed in a mouse model of hyperglycemia

This study aimed to investigate potential functional changes in retinal ganglion cells (RGCs) in a mouse model of hyperglycemia and explore possible therapeutic approaches. Hyperglycemia resembling type 1 diabetes mellitus (DM) was induced in C57BL/6 mice through intraperitoneal injection of streptozotocin (STZ). Blood glucose levels were confirmed to be elevated after 1 week and 4 weeks of injection. Mice with blood glucose levels above 350 mg/mL after 4 weeks of one-dose STZ injection were considered hyperglycemic. The light sensitivity of ON alpha (α) retinal ganglion cells (RGCs), not OFF αRGCs, was reduced in the hyperglycemic mouse model. The number of apoptotic cells, RGCs, and amacrine cells (ACs) remained unaffected at this stage. Similarly, the eletroretinogram (ERG) and optokinetic test results showed no significant differences. The application of picrotoxin (PTX) to block GABA receptors could increase the light sensitivity of ON αRGCs by 1 log unit in hyperglycemic mice. The results show that ON αRGCs may be more susceptible to microenvironmental changes caused by hyperglycemia than OFF αRGCs. This decline in light sensitivity may occur before cell apoptosis during the early stages of the hyperglycemic mouse model but has the potential to be reversed.

Efficacy of Human Recombinant Growth Hormone in Females of a Non-Obese Hyperglycemic Mouse Model after Birth with Low Birth Weight.

We examined whether the administration of growth hormone (GH) improves insulin resistance in females of a non-obese hyperglycemic mouse model after birth with low birth weight (LBW), given that GH is known to increase muscle mass. The intrauterine Ischemia group underwent uterine artery occlusion for 15 min on day 16.5 of gestation. At 4 weeks of age, female mice in the Ischemia group were divided into the GH-treated (Ischemia-GH) and non-GH-treated (Ischemia) groups. At 8 weeks of age, the glucose metabolism, muscle pathology, and metabolome of liver were assessed. The insulin resistance index improved in the Ischemia-GH group compared with the Ischemia group (p = 0.034). The percentage of type 1 muscle fibers was higher in the Ischemia-GH group than the Ischemia group (p < 0.001); the muscle fiber type was altered by GH. In the liver, oxidative stress factors were reduced, and ATP production was increased in the Ischemia-GH group compared to the Ischemia group (p = 0.014), indicating the improved mitochondrial function of liver. GH administration is effective in improving insulin resistance by increasing the content of type 1 muscle fibers and improving mitochondrial function of liver in our non-obese hyperglycemic mouse model after birth with LBW.

PIEZO1 as a new target for hyperglycemic stress-induced neuropathic injury: The potential therapeutic role of bezafibrate

Hyperglycemic stress can directly lead to neuronal damage. The mechanosensitive ion channel PIEZO1 can be activated in response to hyperglycemia, but its role in hyperglycemic neurotoxicity is unclear. The role of PIEZO1 in hyperglycemic neurotoxicity was explored by constructing a hyperglycemic mouse model and a high-glucose HT22 cell model. The results showed that PIEZO1 was significantly upregulated in response to high glucose stress. In vitro experiments have shown that high glucose stress induces changes in neuronal cell morphology and membrane tension, a key mechanism for PIEZO1 activation. In addition, high glucose stress upregulates serum/glucocorticoid-regulated kinase-1 (SGK1) and activates PIEZO1 through the Ca2+ pool and store-operated calcium entry (SOCE). PIEZO1-mediated Ca2+ influx further enhances SGK1 and SOCE, inducing intracellular Ca2+ peaks in neurons. PIEZO1 mediated intracellular Ca2+ elevation leads to calcium/calmodulin-dependent protein kinase 2α (CaMK2α) overactivation, which promotes oxidative stress and apoptosis signalling through p-CaMK2α/ERK/CREB and ox-CaMK2α/MAPK p38/NFκB p65 pathways, subsequently inducing synaptic damage and cognitive impairment in mice. The intron miR-107 of pantothenic kinase 1 (PANK1) is highly expressed in the brain and has been found to target PIEZO1 and SGK1. The PANK1 receptor is activated by peroxisome proliferator-activated receptor α (PPARα), an activator known to upregulate miR-107 levels in the brain. The clinically used lipid-lowering drug bezafibrate, a known PPARα activator, may upregulate miR-107 through the PPARɑ/PANK1 pathway, thereby inhibiting PIEZO1 and improving hyperglycemia-induced neuronal cell damage. This study provides a new idea for the pathogenesis and drug treatment of hyperglycemic neurotoxicity and diabetes-related cognitive dysfunction.

High-fat and high-sucrose diet impairs female reproduction by altering ovarian transcriptomic and metabolic signatures

BackgroundExcessive energy intake in modern society has led to an epidemic surge in metabolic diseases, such as obesity and type 2 diabetes, posing profound threats to women’s reproductive health. However, the precise impact and underlying pathogenesis of energy excess on female reproduction remain unclear.MethodsWe established an obese and hyperglycemic female mouse model induced by a high-fat and high-sucrose (HFHS) diet, then reproductive phenotypes of these mice were evaluated by examing sexual hormones, estrous cycles, and ovarian morphologies. Transcriptomic and precise metabolomic analyses of the ovaries were performed to compare the molecular and metabolic changes in HFHS mice. Finally, orthogonal partial least squares discriminant analysis was performed to compare the similarities of traits between HFHS mice and women with polycystic ovary syndrome (PCOS).ResultsThe HFHS mice displayed marked reproductive dysfunctions, including elevated serum testosterone and luteinizing hormone levels, irregular estrous cycles, and impaired folliculogenesis, mimicking the clinical manifestations of women with PCOS. Precise metabolomic overview suggested that HFHS diet disrupted amino acid metabolism in the ovaries of female mice. Additionally, transcriptional profiling revealed pronounced disturbances in ovarian steroid hormone biosynthesis and glucolipid metabolism in HFHS mice. Further multi-omics analyses unveiled prominent aberration in ovarian arginine biosynthesis pathway. Notably, comparisons between HFHS mice and a cohort of PCOS patients identified analogous reproductive and metabolic signatures.ConclusionsOur results provide direct in vivo evidence for the detrimental effects of overnutrition on female reproduction and offer insights into the metabolic underpinnings of PCOS.

Enhancing human islet xenotransplant survival and function in diabetic immunocompetent mice through LRH-1/NR5A2 pharmacological activation.

The intricate etiology of type 1 diabetes mellitus (T1D), characterized by harmful interactions between the immune system and insulin-producing beta cells, has hindered the development of effective therapies including human islet transplantation, which requires strong immunosuppressants that impair beta cell survival and function. As such alternative immunomodulating therapies are required for successful transplantation. The discovery that pharmacological activation of the nuclear receptor LRH-1/NR5A2 can reverse hyperglycemia in mouse models of T1D by altering, and not suppressing the autoimmune attack, prompted us to investigate whether LRH-1/NR5A2 activation could improve human islet function/survival after xenotransplantation in immunocompetent mice. Human islets were transplanted under the kidney capsule of streptozotocin (STZ)-induced diabetic mice, and treatment with BL001 (LRH-1/NR5A2 agonist) or vehicle was administered one week post-transplant. Our study, encompassing 3 independent experiments with 3 different islet donors, revealed that mice treated for 8 weeks with BL001 exhibited lower blood glucose levels correlating with improved mouse survival rates as compared to vehicle-treated controls. Human C-peptide was detectable in BL001-treated mice at both 4 and 8 weeks indicating functional islet beta cells. Accordingly, in mice treated with BL001 for 8 weeks, the beta cell mass was preserved, while a significant decrease in alpha cells was observed compared to mice treated with BL001 for only 4 weeks. In contrast, vehicle-treated mice exhibited a reduction in insulin-expressing cells at 8 weeks compared to those at 4 weeks. These results suggest that BL001 significantly enhances the survival, engraftment, and functionality of human islets in a STZ-induced diabetic mouse model.

Porphyra haitanensis glycoprotein regulates glucose homeostasis: targeting the liver.

In this study, we investigated the effects of glycoprotein (PG)-mediated regulation of Porphyra haitanensis on liver glucose metabolism in hyperglycemic mouse models, and sought to establish the underlying mechanism, as determined by the changes in liver gene expression and metabolic profiles. The results showed that 30-300 mg kg-1 PG upregulated the expression of the liver genes Ins1, Ins2, Insr, Gys2, Gpi1, Gck, and downregulated the expression of G6pc, G6pc2, and G6pc3, in a concentration-dependent manner. 300 mg kg-1 PG downregulated the concentrations of glucose-related metabolites in the liver, but upregulated lactic acid, 2-aminoacetic acid, and glucose-1-phosphate concentrations. It was assumed that PG regulated liver glucose metabolism by enriching insulin secretion, glycolysis/gluconeogenesis, and the AMPK signaling pathway, and promoting insulin secretion, glycogen synthesis, and glycolysis. Our findings supported the development of P. haitanensis and its glycoproteins as novel natural antidiabetic compounds that regulated blood glucose homeostasis.

Increased glucose availability sensitizes pancreatic cancer to chemotherapy

Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes. We show that a hyperglycemic state substantially enhances the efficacy of conventional single- and multi-agent chemotherapy regimens against PDAC. Molecular analyses of tumors exposed to high glucose levels reveal that the expression of GCLC (glutamate-cysteine ligase catalytic subunit), a key component of glutathione biosynthesis, is diminished, which in turn augments oxidative anti-tumor damage by chemotherapy. Inhibition of GCLC phenocopies the suppressive effect of forced hyperglycemia in mouse models of PDAC, while rescuing this pathway mitigates anti-tumor effects observed with chemotherapy and high glucose.

Proinflammatory Cytokines Trigger the Onset of Retinal Abnormalities and Metabolic Dysregulation in a Hyperglycemic Mouse Model.

Recent evidence has shown that retinal inflammation is a key player in diabetic retinopathy (DR) pathogenesis. To further understand and validate the metabolic biomarkers of DR, we investigated the effect of intravitreal proinflammatory cytokines on the retinal structure, function, and metabolism in an in vivo hyperglycemic mouse model. C57Bl/6 mice were rendered hyperglycemic within one week of administration of a single high-dose intraperitoneal injection of streptozotocin, while control mice received vehicle injection. After confirming hyperglycemia, the mice received an intravitreal injection of either proinflammatory cytokines (TNF-α and IL-1β) or vehicle. Similarly, control mice received an intravitreal injection of either proinflammatory cytokines or vehicle. The retinal structure was evaluated using fundus imaging and optical coherence tomography, and retinal function was assessed using a focal electroretinogram (ERG), two days after cytokine injection. Retinas were collected for biochemical analysis to determine key metabolite levels and enzymatic activities. Hyperglycemic mice intraocularly injected with cytokines developed visible retinal vascular damage and intravitreal and intraretinal hyper-reflective spots two days after the cytokines injection. These mice also developed a significant functional deficit with reduced a-wave and b-wave amplitudes of the ERG at high light intensities compared to control mice. Furthermore, metabolic disruption was evident in these mice, with significantly higher retinal glucose, lactate, ATP, and glutamine levels and a significant reduction in glutamate levels compared with control mice. Minimal or no metabolic changes were observed in hyperglycemic mice without intraocular cytokines or in control mice with intraocular cytokines at 2 days post hyperglycemia. Proinflammatory cytokines accelerated the development of vascular damage in the eyes of hyperglycemic mice. Significant changes were observed in retinal structure, function, and metabolic homeostasis. These findings support the idea that with the onset of inflammation in DR, there is a deficit in metabolism. Therefore, early intervention to prevent inflammation-induced retinal changes in diabetic patients may improve the disease outcome.

Selenium-Enriched and Ordinary Black Teas Regulate the Metabolism of Glucose and Lipid and Intestinal Flora of Hyperglycemic Mice.

Black tea is one of the six major tea categories and has a variety of bioactivities. However, little is known about its comprehensive evaluation of hypoglycemic effects and potential mechanisms. In this study, we investigated the in vivo hypoglycemic activity and potential mechanism for aqueous extracts of ordinary black tea (BT) and selenium-enriched black tea (Se-BT) by using an established high-fat diet together with streptozotocin (STZ)-induced hyperglycemic mouse model. Additionally, we also explored their α-glucosidase inhibition activity. The results show that both BT and Se-BT had a favorable glycosidase inhibitory activity. Moreover, the intervention of BT and Se-BT could regulate the mRNA expression and the level of serum parameters related to glucose and lipid metabolisms. Accordingly, they could activate the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) signaling pathway and alleviate insulin resistance (IR) and hyperglycemia. Moreover, supplementation of BT and Se-BT increased the richness and diversity of intestinal flora and altered the abundance of beneficial and harmful bacteria. Both BT and Se-BT could regulate glucose metabolism, alleviate tissue damage, and restore intestinal flora dysbiosis, suggesting that they could be used as a natural functional food for preventing hyperglycemia.

Experimentally Induced Hyperglycemia in Prepubertal Phase Impairs Oocyte Quality and Functionality in Adult Mice.

Reproductive abnormalities in women with a history of childhood diabetes are believed to be partially attributed to hyperglycemia. Prolonged hyperglycemia can negatively affect ovarian function and fertility during reproductive life. To address this in an experimental setting, the present study used streptozotocin-induced hyperglycemic prepubertal mouse model. The impact of prolonged hyperglycemic exposure during prepubertal life on ovarian function, oocyte quality, and functional competence was assessed in adult mice. The ovarian reserve was not significantly altered; however, the in vitro maturation potential (P < 0.001), mitochondrial integrity (P < 0.01), and meiotic spindle assembly (P < 0.05-0.001) in oocytes were significantly affected in hyperglycemic animals in comparison to control groups. The results from the study suggest that prepubertal hyperglycemia can have adverse effects on the oocyte functional competence and spindle integrity during the reproductive phase of life. Because these changes can have a significant impact on the genetic integrity and developmental potential of the embryos and fetus, the observation warrants further research both in experimental and clinical settings.

A Non-Obese Hyperglycemic Mouse Model that Develops after Birth with Low Birthweight.

The number of low birthweight (LBW) infants weighing below 2500 g has not decreased in Japan. This study aimed to develop an adult non-obese hyperglycemic mouse model born with LBW to study the pathogenesis. At 16.5 days of gestation, transient intrauterine ischemia (blocked blood flow in both uterine arteries for 15 min) was performed in a subgroup of pregnant mice (group I). Non-occluded dams were used as sham controls (group C). After birth, female pups in each group were weaned at 4 weeks of age and reared on the normal diet until 8 weeks of age (n = 7). Fasting blood glucose levels, serum immunoreactive insulin (IRI), and body composition were then measured. Metabolite analyses was performed on the liver tissues. Birthweight was significantly lower in group I compared with group C. Pups from group I remained underweight with low fat-free mass and showed hyperglycemia with high serum IRI and homeostasis model assessment of insulin resistance levels, indicating insulin resistance. Metabolite analyses showed significantly reduced adenosine triphosphate and nicotinamide adenine dinucleotide production and increased lactic acid in group I. The pathogenesis of our non-obese hyperglycemic mouse model may be due to increased myogenic insulin resistance based on mitochondrial dysfunction and reduced lean body mass.

1394-P: Peri-Islet Glial-Cell Expansion Occurs in Response to High-Fat Diet-Induced Obesity and Hyperglycemia

Peri-islet glial cells (PIGCs) are positioned to control neuronal-endocrine-vascular cell communication within the islet, but their role in islet cell function is not known. Hypothalamic glial cells become reactive in response to high fat diet (HFD) feeding and are implicated in the pathogenesis of obesity and type 2 diabetes. We hypothesize that metabolic stress such as diet-induced obesity and hyperglycemia promote the expansion of PIGCs, similar to what has been observed in the central nervous system. To test this hypothesis, we used the glial cell marker, glial fibrillary acidic protein (GFAP) , to identify PIGCs and compared GFAP immunoreactivity in pancreas from the following groups. First, pancreas was harvested from HFD- or chow fed control C57BL/6J male mice after 2 days, 2 weeks or 8 weeks on diet (n=6-8/group) . Second, pancreas was taken from 12-wk old db/db male mice and their control littermates with or without empagliflozin (EMPA) treatment (20mg/kg/d for 6 weeks; n=4-7/group) . Islet PIGC area was quantified as GFAP-positive area/total islet area x100%. Mann-Whitney test and one-way ANOVA were used for data analysis. We found that HFD feeding increased mouse pancreatic peri-islet GFAP expression relative to chow controls at 2 days (HFD 1.4±0.2%, chow 0.8±0.1%; p=0.02) , 2 weeks (HFD 3.5±0.4%, chow 1.2±0.1%; p&amp;lt;0.001) and 8 weeks (HFD 5.4±0.3%, chow 1.8±0.2%; p=0.002) in association with body weight gain and impaired glucose tolerance. Similar results were observed in obese and hyperglycemic db/db mouse vs. control littermates (db/db 5.0±1.4%, control 1.2±0.4%; p=0.004) . There was a trend for EMPA treatment to reduce islet PIGC area in the db/db mice (EMPA 2.0±0.5, VEH 5.0±1.4%, p=0.08) . In conclusion, these findings indicate that islet gliosis is observed in two obese and hyperglycemic mouse models and raise the possibility that pancreatic ‘gliosis’ may have a relevant role in islet-cell function regulation under metabolic challenge. Disclosure J.Niu: None. J.B.Moss: None. W.Rosario: Employee; Merck &amp; Co., Inc. R.Arumugam: None. D.J.Hackney: None. R.L.Hull-meichle: Research Support; Casma Therapeutics. J.Tong: None. Funding National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (R01DK097550) ;Department of Veterans Affairs (IBX004063)

1473-P: Combination Therapy with Dual-Function Peptide S1K and Insulin Reduces Blood Glucose Levels in Mouse Models of Type 1 Diabetes through Beta-Cell Regeneration and Immunosuppression

β cell regeneration is necessary to cure patients with type 1 diabetes (T1D) whose β cells are destroyed by immune cells. Although insulin therapy can control blood glucose levels, it must be administered throughout life and occurs several side effects such as hypoglycemia. New β cell can be generated through neogenesis, β cell replication or transdifferentiation from other cells in diabetic animals. In addition to β cell regeneration, immunosuppression is another important mechanism to prevent β cell destruction, but currently any drugs haven’t been approved as immunosuppressants for T1D treatments yet. A novel 9-mer peptide, Shiloah 1000 (S1K) , has dual functions of β cell regeneration and immunosuppression. In streptozotocin-induced hyperglycemic mouse model, the number of mice recovered to normoglycemia was increased by the combined treatment of S1K and insulin compared to S1K or insulin alone. In addition, the combined treatment more increased the number of β cells than S1K or insulin alone. Interestingly, insulin/glucagon double-positive cells were increased by both combined and S1K alone treatments. The increase in the number of mice recovered to normoglycemia is considered to be due to β cell regeneration through α- to β-cell transdifferentiation by S1K. In the NOD mouse model, the combined treatment of S1K and insulin suppressed hyperglycemia more than insulin alone. In addition, the serum C-peptide levels were increased by both combined and S1K treatments, but not by insulin treatment. The increase in the serum C-peptide level suggest that β cells remain undestroyed by immunosuppression. Taken together, our data show that S1K, as a drug candidate for T1D treatment in combination with insulin reduces blood glucose levels in the T1D mouse models through β cell regeneration and immunosuppression, suggesting a potential role in preventing and curing T1D. Disclosure Y. Lee: Employee; Ensolbiosciences. H. Kim: Employee; Ensolbiosciences. J. Kim: Employee; Ensol Bioscience. Y. Jang: Employee; Ensolbiosciences.

NR5A2/LRH-1 regulates the PTGS2-PGE2-PTGER1 pathway contributing to pancreatic islet survival and function

SummaryLRH-1/NR5A2 is implicated in islet morphogenesis postnatally, and its activation using the agonist BL001 protects islets against apoptosis, reverting hyperglycemia in mouse models of Type 1 Diabetes Mellitus. Islet transcriptome profiling revealed that the expression of PTGS2/COX2 is increased by BL001. Herein, we sought to define the role of LRH-1 in postnatal islet morphogenesis and chart the BL001 mode of action conferring beta cell protection. LRH-1 ablation within developing beta cells impeded beta cell proliferation, correlating with mouse growth retardation, weight loss, and hypoglycemia leading to lethality. LRH-1 deletion in adult beta cells abolished the BL001 antidiabetic action, correlating with beta cell destruction and blunted Ptgs2 induction. Islet PTGS2 inactivation led to reduced PGE2 levels and loss of BL001 protection against cytokines as evidenced by increased cytochrome c release and cleaved-PARP. The PTGER1 antagonist—ONO-8130—negated BL001-mediated islet survival. Our results define the LRH-1/PTGS2/PGE2/PTGER1 signaling axis as a key pathway mediating BL001 survival properties.

PCSK9 deficiency protects against ischemic stroke but increases hemorrhagic transformation in a hyperglycemic mouse model

Background and Aims: PCSK9 inhibitors can reduce LDL cholesterol down to extremely low levels. Despite PCSK9 inhibitors undisputed cardiovascular benefits, a relationship between very low LDL-C and the risk of hemorrhagic transformation (HT) following ischemic stroke has been suggested. The aim of the present study was to assess HT in PCSK9 knockout mice.

High Glucose-Aggravated Hepatic Insulin Resistance: Role of the NLRP3 Inflammasome in Kupffer Cells.

This study aimed to investigate whether the NLRP3 inflammasome in Kupffer cells (KCs) can be activated in response to high glucose (HG) and toevaluate its influence on hepatic insulin sensitivity. Primary KCs and hepatocytes were isolated from mice, and lipid accumulation, glucose output, and insulin sensitivity of hepatocytes were investigated after culturing either alone or with KCs exposed to HG. The influence of HG-induced NLRP3 inflammasome activation in KCs on insulin sensitivity of hepatocytes was examined. Treatment with gadolinium trichloride caused KC depletion, and, subsequently, a streptozotocin-induced hyperglycemic mouse model was used to confirm the influence of KCs on hepatic insulin sensitivity. Hepatocytes cocultured with KCs showed enhanced lipid accumulation, glucose output, and impaired insulin sensitivity when exposed to HG. Enhanced NLRP3 inflammasome activation was also evident in both hepatocytes and KCs. Moreover, KCs that were pretreated with caspase-1 inhibitor, NLRP3 inhibitor, and NLRP3 smallinterfering RNA corrected coculture-induced aberrances in insulin action and NLRP3 inflammasome activation in hepatocytes. KC coculture also increased interleukin-1β (IL-1β)-mediated nuclear factor-κB (NF-κB) activation in hepatocytes. In hyperglycemic mice, KC depletion inhibited NLRP3 inflammasome activation and improved hepatic insulin sensitivity. NLRP3 inflammasome activation impaired insulin sensitivity through KC-derived IL-1β-mediated NF-κB activation in hepatocytes exposed to HG.

Heparin inhibits proinflammatory and promotes anti-inflammatory macrophage polarization under hyperglycemic stress

Monocytes are rapidly recruited to sites of diabetic complications and differentiate into macrophages. Previously, we showed that rat kidney mesangial cells dividing during hyperglycemic stress abnormally synthesize hyaluronan (HA) in intracellular compartments. This initiates a stress response, resulting in an extracellular HA matrix after division that recruits inflammatory cells. Cell-cell communication among macrophages that are recruited into the glomeruli and the damaged rat mesangial cells leads to diabetic nephropathy, fibrosis, and proteinurea, which are inhibited in heparin-treated diabetic rats. In this study, we found that murine bone marrow-derived macrophages (BMDMs) and a human leukemic cell line, U937 cells, dividing in hyperglycemia also accumulate intracellular HA and that heparin inhibits the HA accumulation. Both cell types expressed increased levels of proinflammatory markers: inducible nitric-oxide synthase and tumor necrosis factor-α, when cultured under hyperglycemic stress, which was inhibited by heparin. Furthermore, the abnormal intracellular HA was also observed in peripheral blood monocytes derived from three different hyperglycemic diabetic mouse models: streptozotocin-treated, high-fat fed, and Ins2Akita. Moreover, peripheral blood monocytes in humans with type 2 diabetes and poorly controlled blood glucose levels (hemoglobin A1c (HbA1c) levels of >7) also had intracellular HA, whereas those with HbA1c of <7, did not. Of note, heparin increased the anti-inflammatory markers arginase 1 and interleukin-10 in murine BMDMs. We conclude that heparin treatment of high glucose-exposed dividing BMDMs promotes an anti-inflammatory tissue-repair phenotype in these cells.

DPP-4 Inhibitor Linagliptin is Neuroprotective in Hyperglycemic Mice with Stroke via the AKT/mTOR Pathway and Anti-apoptotic Effects.

Dipeptidyl peptidase 4 (DPP-4) inhibitors have been shown to have neuroprotective effects in diabetic patients suffering from stroke, but less research has focused on patients with mild hyperglycemia below the threshold for a diagnosis of diabetes. In this investigation, a hyperglycemic mouse model was generated by intraperitoneal injection of streptozotocin and then subjected to focal cerebral ischemia. We demonstrated that the DPP-4 inhibitor linagliptin significantly decreased the infarct volume, reduced neuronal cell death, decreased inflammation, and improved neurological deficit compared with control mice. Linagliptin up-regulated the expression of p-Akt and p-mTOR and regulated the apoptosis factors Bcl-2, Bax, and caspase 9. Taken together, these results suggest that linagliptin exerts a neuroprotective action likely through activation of the Akt/mTOR pathway along with anti-apoptotic and anti-inflammatory mechanisms. Therefore, linagliptin may be considered as a therapeutic treatment for stroke patients with mild hyperglycemia.

The potential of instant yellow cornmeal and tempe flour as glucose control on hyperglycemic conditions

The objective of this study to evaluate the glucose control potential of instant yellow cornmeal and tempe flour by using hyperglycemic mouse models. In approaching this purpose, 24 male ddY mice were used and divided into 3 goups : group A (positive control group, hyperglycemic, 100 % standard feed), group B (treatment group, hyperglycemic, 60 % instant yellow cornmeal + 40 % instant tempe flour), and group C (negative control group, normal, 100 % standard feed). The evaluated parameters of body weight and blood glucose levels were measured during the 8-week period of the study. Results showed that group B (60 % instant yellow cornmeal + 40 % instant tempe flour ration) indicated the potential to control hyperglycemic conditions (p<0.05 ) and displayed higher levels of body weight (6.05 ± 6.08 grams, p >0.05 ) compared to groups A and C.

345 Skin insulin resistance impairs skin barrier function in hyperglycemic and diabetic mouse models

345 Skin insulin resistance impairs skin barrier function in hyperglycemic and diabetic mouse models