Modulate Glucose Levels Research Articles

Effect of Combined Treatment with Levofloxacin and Metformin on Diabetes-the Diabetes Related Behavioral and Biochemical Alterations.

The current experiment was conducted to investigate the combined effect of levofloxacin (LVX) and metformin treatment on blood glucose levels, malondialdehyde (MDA),nitrite levels, and anxiety in streptozotocin (STZ)+ nicotine adenine dinucleotide (NAD)-induced diabetic rats. In this study, Wistar rats have been used. After receiving a single dose of STZ + NAD (45 mg/kg, i.p.+ 50 mg/kg, i.p.), the rats developed diabetes. Glucose levels in diabetic rats exceeded 200 mg/dL (verified on the third day). Saline was administered to non-diabetic rats (controls). Thediabetic rats were administered metformin (50 mg/kg, p.o.), LVX (30 mg/kg, i.p.), or metformin + LVX for 14 days. Blood samples were obtained after the 14th day of therapy, and the rats were given behavioral parameters to determine locomotor activity and anxiety level. Blood plasma samples were separately collected for the determination of nitrite and MDA levels. It was observed that the combined treatment of metformin and LVX significantly increased glucose levels in the blood of diabetic rats compared with diabetic control (p < 0.05) and diabetic rats treated with metformin alone (p < 0.001) at days 3 and 7. Further, combined treatment of metformin and LVX significantly reduced time spent at the center of the open field test (p < 0.001), significantly reduced time spent and entry made in the light chamber of the light-dark test (p < 0.001), significantly increased time spent in the open arm and reduced the time spent in the closed arm of the Elevated plus maze (p < 0.001) compared with alone metformin-treated diabetic rats. Further, combined treatment with metformin and LVX significantly increased the nitrite level, (p < 0.001) but reduced the MDA level in plasma compared with metformin alone-treated diabetic rats (p <0.001). The present study suggests that combined treatments with levofloxacin and metformin may modulate glucose levels and anxiety-related activity.

Alpha cells as targets for incretin therapy

Abstract The pivotal role of alpha cells in glucose homeostasis, primarily through glucagon secretion, necessitates a deeper understanding of their potential as therapeutic targets in diabetes management. This narrative review explores the emerging paradigm of incretin-based therapies targeting alpha cells to ameliorate hyperglycemia associated with diabetes. Amidst the prevailing focus on beta cells, this review accentuates the lesser-explored potential of alpha cells in modulating glucose levels. Incretin hormones, notably glucagon-like peptide-1 (GLP-1), not only augment insulin secretion but also inhibit glucagon release, thereby acting as a dual mechanism for glucose control. Contemporary pharmaceutical agents like GLP-1 receptor agonists and DPP-4 inhibitors exhibit promise in modulating alpha-cell function, with evidence suggesting their efficacy in reducing postprandial glucagon and improving glycemic control. Clinical trials evince a favorable safety profile with minimal hypoglycemia risk. Moreover, DPP-4 inhibitors demonstrate a unique potential in reducing glycemic variability by nuanced modulation of alpha-cell activity. This review underscores the imperative for further research to elucidate the molecular pathways underpinning alpha-cell dysfunction in diabetes and to explore combinatory regimens for optimizing glycemic control. The insights garnered could pave the way for novel therapeutic strategies, enriching the armamentarium against diabetes through a more holistic approach targeting both alpha and beta cells.

Curcumin in Retinal Diseases: A Comprehensive Review from Bench to Bedside.

Recent evidence in basic science is leading to a growing interest in the possible role of curcumin in treating retinal diseases. Curcumin has been demonstrated to be able to modulate gene transcription and reduce ganglion cell apoptosis, downgrade VEGF, modulate glucose levels and decrease vascular dysfunction. So far, the use of curcumin has been limited by poor bioavailability; to overcome this issue, different types of carriers have been used. Multiple recent studies disclosed the efficacy of using curcumin in treating different retinal conditions. The aim of this review is to comprehensively review and discuss the role of curcumin in retinal diseases from bench to bedside.

Effect of Transcutaneous Radial Artery Photobiomodulation on Continuous Measures of Interstitial Glucose in a Single Subject: A Brief Report.

Background: Intravenous blood irradiation with light is purported to reduce blood sugar levels in people with diabetes mellitus (DM). Transcutaneous light emitting devices are marketed for use in modulating glucose levels, yet evidence of effectiveness is scarce. Materials and methods: In a single subject (nondiabetic woman with significant family history of DM), transcutaneous photobiomodulation (PBM) at various wavelengths was applied to the radial artery immediately after a standardized meal, or at the peak glucose after the standardized meal. Data were compared with a "no intervention" control period. Interstitial glucose was measured every 5 min until return to baseline. Results: A single transcutaneous application of PBM at wavelength and dose combinations tested and when applied immediately after a test meal or at peak glucose postprandially did not affect interstitial glucose levels in a woman without DM. Conclusions: Future studies could include testing additional subjects, using repeated PBM applications and monitoring using blood glucose.

Effects of saffron supplementation on glycemia and inflammation in patients with type 2 diabetes mellitus: A randomized double-blind, placebo-controlled clinical trial study

BackgroundNew evidence indicates that overproduction of pro-inflammatory cytokines is responsible for the development of diabetes difficulties. Some herbals such as saffron, may control inflammation and improve the hyperglycemic states in diabetic patients. Therefore, this investigation aimed to assess the effects of saffron supplementation on fasting glucose and inflammatory markers levels in patients with type2 diabetes mellitus (T2DM). MethodsIn this randomized double-blind, placebo-controlled clinical trial, 60 T2DM patients were randomly assigned into two groups as saffron and placebo (n = 30) receiving 100 mg/day saffron powder or starch capsules (1 capsule) for a duration of 8 weeks. Fasting blood sample was collected at baseline and at the end of the intervention. Fasting blood glucose (FBG) was immediately analyzed by the auto-analyzer. The serum level of Interleukin −6 (IL-6), Tumor necrosis factor-alpha (TNF-α), and Interleukin-10 (IL-10) were measured using ELISA assay by laboratory kits. Also, Real-time quantitative reverse transcription (RT-PCR) assay measured the expression level of TNF-α, IL-6, and IL-10 at the mRNA level. ResultsSaffron supplementation significantly decreased the FBG levels within 8 weeks compared to placebo (130.93 ± 21.21 vs 135.13 ± 23.03 mg/dl, P = 0.012). Moreover, the serum level of TNF-α notably reduced in the saffron group compared to the placebo group (114.40 ± 24.28 vs 140.90 ± 25.49 pg/ml, P < 0.001). Also, saffron supplementation significantly down-regulated the expressions of TNF-α (P = 0.035) and IL-6 mRNA levels (P = 0.014). ConclusionIn our study, it was indicated that saffron modulates glucose levels as well as inflammation status in T2DM patients through decreasing the expressions levels of some inflammatory mediators. Also, further investigations are necessary to confirm the positive effects of saffron as a complementary therapy for T2DM patients.

Sumitomo licenses diabetes drug

Sumitomo Dainippon Pharma will pay $42 million up front for the right to develop Poxel’s type 2 diabetes treatment imeglimin in several Asian countries, including Japan and China. Poxel is in talks with Japanese regulators about the design of three Phase III studies slated to begin there by the end of this year. Poxel is looking for a partner to develop the compound in the U.S. and Europe. While currently marketed diabetes drugs modulate glucose levels, Poxel’s drug increases the amount of glucose excreted in urine.

Manipulating Glucose Metabolism during Different Stages of Viral Pathogenesis Can Have either Detrimental or Beneficial Effects.

This report deals with physiological changes and their implication following ocular infection with HSV. This infection usually results in a blinding inflammatory reaction in the cornea, orchestrated mainly by proinflammatory CD4 T cells and constrained in severity by regulatory T cells. In the present report, we make the unexpected finding that blood glucose levels change significantly during the course of infection. Whereas levels remained normal during the early phase of infection when the virus was actively replicating in the cornea, they increased around 2-fold during the time when inflammatory responses to the virus was occurring. We could show that glucose levels influenced the extent of induction of the inflammatory T cell subset in vitro that mainly drives lesions, but not regulatory T cells. Additionally, if glucose utilization was limited in vivo as a consequence of therapy in the inflammatory phase with the drug 2-deoxy-glucose (2DG), lesions were diminished compared with untreated infected controls. In addition, lesions in 2DG-treated animals contained less proinflammatory effectors. Glucose metabolism also influenced the acute phase of infection when the replicating virus was present in the eye. Thus, therapy with 2DG to limit glucose utilization caused mice to become susceptible to the lethal effects of HSV infection, with the virus spreading to the brain causing encephalitis. Taken together, our results indicate that glucose metabolism changed during the course of HSV infection and that modulating glucose levels can influence the outcome of infection, being detrimental or beneficial according to the stage of viral pathogenesis.

Exendin-4 Inhibits Matrix Metalloproteinase-9 Activation and Reduces Infarct Growth After Focal Cerebral Ischemia in Hyperglycemic Mice.

Admission hyperglycemia is an independent risk factor for poor outcome of ischemic stroke. Amelioration of hyperglycemia by insulin has not been shown to improve the poststroke outcome. Glucagon-like peptide 1 receptor agonists, which modulate glucose levels by stimulating insulin secretion, have been shown to exert cytoprotective effects by inhibiting inflammation and oxidative stress. This study aimed to evaluate whether the glucagon-like peptide 1 receptor agonist exendin-4 could reduce glucose levels and exert protective effects after acute focal ischemia in hyperglycemic mice. Hyperglycemia was induced by intraperitoneal injection of dextrose 15 minutes before transient middle cerebral artery occlusion was performed for 60 minutes using an intraluminal thread. We assessed 4 groups: (1) normal glucose (vehicle control), (2) induced hyperglycemia, (3) induced hyperglycemia with insulin treatment, and (4) induced hyperglycemia with exendin-4 treatment. Neurovascular injuries in brains from each group were evaluated 24 hours and 7 days post ischemia. Hyperglycemia significantly increased infarct volume (36.3±1.20 versus 26.9±1.28; P<0.001), brain edema (P<0.05), and hemorrhagic transformation compared with control (P<0.001). This increase in infarct volume was associated with increased blood-brain barrier disruption and matrix metalloproteinase-9 activation. Exendin-4, but not insulin, attenuated matrix metalloproteinase-9 activation, proinflammatory cytokine (tumor necrosis factor-α) release, and biomarkers of oxidative stress and showed significant inhibition of infarct growth at 24 hours (23.6±0.97 versus 36.3±1.20; P<0.001) and at 7 days after ischemia (21.0±0.92 versus 29.3±1.41; P<0.001). Treatment with exendin-4 could be a potentially useful therapeutic option for treatment of acute ischemic stroke with transient hyperglycemia.

Glycogen Phosphorylase Inhibitor N-(3,5-Dimethyl-Benzoyl)-N’-(β-D-Glucopyranosyl)Urea Improves Glucose Tolerance under Normoglycemic and Diabetic Conditions and Rearranges Hepatic Metabolism

Glycogen phosphorylase (GP) catalyzes the breakdown of glycogen and largely contributes to hepatic glucose production making GP inhibition an attractive target to modulate glucose levels in diabetes. Hereby we present the metabolic effects of a novel, potent, glucose-based GP inhibitor (KB228) tested in vitro and in vivo under normoglycemic and diabetic conditions. KB228 administration enhanced glucose sensitivity in chow-fed and obese, diabetic mice that was a result of higher hepatic glucose uptake. Besides improved glucose sensitivity, we have observed further unexpected metabolic rearrangements. KB228 administration increased oxygen consumption that was probably due to the overexpression of uncoupling protein-2 (UCP2) that was observed in animal and cellular models. Furthermore, KB228 treatment induced mammalian target of rapamycin complex 2 (mTORC2) in mice. Our data demonstrate that glucose based GP inhibitors are capable of reducing glucose levels in mice under normo and hyperglycemic conditions. Moreover, these GP inhibitors induce accommodation in addition to GP inhibition - such as enhanced mitochondrial oxidation and mTORC2 signaling – to cope with the glucose influx and increased glycogen deposition in the cells, however the molecular mechanism of accommodation is unexplored.

From Structure – Based to Knowledge – Based Drug Design Through X-Ray Protein Crystallography: Sketching Glycogen Phosphorylase Binding Sites

The knowledge derived from the three-dimensional structure of a macromolecular receptor either in the native form or in complex with different ligands has given new insights to the development of improved drug candidates contributing to the drug development pipeline. The structure-based drug design approach has been tested on a number of macromolecular targets implicated in various diseases such as hypertension, glaucoma, HIV and influenza. This approach has also been employed for the development of new antidiabetic agents targeting glycogen phosphorylase (GP), an enzyme that modulates glucose levels in blood circulation. The key role of x-ray protein crystallography in the structure-based inhibitor design process is presented by the case of rabbit muscle GP (RMGPb) that shares increased homology with the liver isoenzyme. The properties of the allosteric binding sites of RMGPb are revealed by filing the interactions formed upon binding of characteristic functional groups and documenting the changes induced in the residues lining the site of interest.

Local, exendin-(9-39)-insensitive, site of action of GLP-1 in canine ileum.

Glucagon-like peptide-1 (GLP-1) modulates glucose levels following a meal, including by inhibition of gastric emptying and intestinal transport. Intra-arterial injection of GLP-1 into the gastric corpus, antrum, or pylorus of anesthetized dogs had no effect on the contractile activity of the resting or neurally activated stomach. GLP-1 injected intra-arterially inhibited intestinal segments when activated by enteric nerve stimulation but not by acetylcholine. Isolated ileum segments were perfused intra-arterially, instrumented with strain gauges to record circular muscle activity and with subserosal electrodes to stimulate enteric nerves. GLP-1 caused concentration-dependent inhibition of nerve-stimulated phasic but not tonic activity. This was absent during TTX-induced activity and partly prevented by N(G)-nitro-L-arginine. Exendin-(9-39), the GLP-1 antagonist, had no intrinsic activity and did not affect the actions of GLP-1. Capsaicin mimicked the effects of GLP-1 and may have reduced the effect of subsequent GLP-1. GLP-1 may mediate paracrine action on afferent nerves in the canine ileal mucosa using an unusual receptor.