latanoprost and Diabetes-Mellitus--Type-2

A 74 year-old woman present with blurry vision of 12 hour duration in her right eye, and with no other symptoms. Biomicroscopic examination revealed a 3 mm hyphaema in her right eye and multiple nodular structures in the pupillary margin of both eyes.. Iris tufts are vascular anomalies unrelated to ischaemia that must be included in the differential diagnosis of spontaneous hyphaema.

Topics: Administration, Topical; Aged; Brimonidine Tartrate; Cyclopentolate; Dexamethasone; Diabetes Mellitus, Type 2; Female; Glaucoma, Open-Angle; Hamartoma; Humans; Hyphema; Iris Diseases; Latanoprost; Microscopy, Acoustic; Ophthalmic Solutions; Prostaglandins F, Synthetic; Quinoxalines; Vision Disorders

Improvement of glucose and lipid metabolic dysfunctions is a potent therapeutic strategy against type 2 diabetes mellitus, and identifying new functions for existing drugs may help accelerate the speed of new drug development. Here, we report that latanoprost, a clinical drug for treating primary open-angle glaucoma and intraocular hypertension, effectively ameliorated glucose and lipid disorders in two mouse models of type 2 diabetes. In addition, the glucose-lowering mechanisms of latanoprost were intensively investigated.. A binding-affinity assay and enzymatic tests were used to determine the targets of latanoprost. Cell-based assays on 3T3-L1 adipocytes and C2C12 myotubes and animal model-based assays with db/db and ob/ob mice were further performed to clarify the mechanisms underlying latanoprost-regulated glucose and lipid metabolism.. Latanoprost functioned as both an indirect activator of AMP-activated protein kinase and a selective retinoid X receptor α (RXRα) antagonist able to selectively antagonise the transcription of a RXRα/peroxisome proliferator-activated receptor γ heterodimer. It promoted glucose uptake, inhibited pre-adipocyte differentiation and regulated the main genes responsible for glucose and lipid metabolism, including Fas, Scd1, Perilipin (also known as Plin1), Lpl and Pdk4. Chronic administration of latanoprost in mice potently decreased the levels of fasting blood glucose, HbA1c, fructosamine (FMN), NEFA and total cholesterol, and effectively improved glucose tolerance and glucose/lipid metabolism-related genes in vivo.. Our studies demonstrate that the existing eye drug latanoprost is both an indirect activator of AMP-activated protein kinase and a selective RXRα antagonist. Latanoprost effectively ameliorated glucose and lipid disorders in diabetic mice, which strongly highlights the potential of latanoprost in the treatment of type 2 diabetes mellitus.

Topics: 3T3-L1 Cells; AMP-Activated Protein Kinases; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drug Design; Glucose; Hypoglycemic Agents; Latanoprost; Lipid Metabolism; Mice; Mice, Inbred NOD; Mice, Obese; Muscle Fibers, Skeletal; PPAR gamma; Prostaglandins F, Synthetic; Remission Induction; Retinoid X Receptor alpha

Results from clinical trials are usually summarized in the form of sampling distributions. When full information (mean, SEM) about these distributions is given, performing meta-analysis is straightforward. However, when some of the sampling distributions only have mean values, a challenging issue is to decide how to use such distributions in meta-analysis. Currently, the most common approaches are either ignoring such trials or for each trial with a missing SEM, finding a similar trial and taking its SEM value as the missing SEM. Both approaches have drawbacks. As an alternative, this paper develops and tests two new methods, the first being the prognostic method and the second being the interval method, to estimate any missing SEMs from a set of sampling distributions with full information. A merging method is also proposed to handle clinical trials with partial information to simulate meta-analysis.. Both of our methods use the assumption that the samples for which the sampling distributions will be merged are randomly selected from the same population. In the prognostic method, we predict the missing SEMs from the given SEMs. In the interval method, we define intervals that we believe will contain the missing SEMs and then we use these intervals in the merging process.. Two sets of clinical trials are used to verify our methods. One family of trials is on comparing different drugs for reduction of low density lipprotein cholesterol (LDL) for Type-2 diabetes, and the other is about the effectiveness of drugs for lowering intraocular pressure (IOP). Both methods are shown to be useful for approximating the conventional meta-analysis including trials with incomplete information. For example, the meta-analysis result of Latanoprost versus Timolol on IOP reduction for six months provided in 1 was 5.05 +/- 1.15 (Mean +/- SEM) with full information. If the last trial in this study is assumed to be with partial information, the traditional analysis method for dealing with incomplete information that ignores this trial would give 6.49 +/- 1.36 while our prognostic method gives 5.02 +/- 1.15, and our interval method provides two intervals as Mean in [4.25, 5.63] and SEM in [1.01, 1.24].. Both the prognostic and the interval methods are useful alternatives for dealing with missing data in meta-analysis. We recommend clinicians to use the prognostic method to predict the missing SEMs in order to perform meta-analysis and the interval method for obtaining a more cautious result.

Topics: Antihypertensive Agents; Cholesterol, LDL; Clinical Trials as Topic; Data Interpretation, Statistical; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Intraocular Pressure; Latanoprost; Meta-Analysis as Topic; Metformin; Ocular Hypertension; Prostaglandins F, Synthetic; Sampling Studies; Sulfonylurea Compounds; Thiazolidinediones; Time Factors; Timolol