[Targeting NMDAR/AMPAR: a promising pharmacotherapeutic approach for depressive disorders]. / Targetirovanie NMDAR/AMPAR ­ perspektivnyi podkhod farmakokorrektsii depressivnykh rasstroistv.

Depression is a leading cause of disability and reduced work capacity worldwide. The monoamine theory of the pathogenesis of depression has remained dominant for many decades, however, drugs developed on its basis have limited efficacy. Exploring alternative mechanisms underlying this pathology could illuminate new avenues for pharmacological intervention. Targeting glutamatergic pathways in the CNS, particularly through modulation of NMDA and AMPA receptors, demonstrates promising results. This review presents some existing drugs with glutamatergic activity and novel developments based on it to enhance the efficacy of pharmacotherapy for depressive disorders.

[Fixed ratio combinations GLP-1RA and basal insulin: literature review].

The progressive nature of type 2 diabetes mellitus leads to the need for insulin therapy in a significant proportion of patients. Very often start of insulin therapy in type 2 diabetes mellitus (T2DM) is associated with weight gain and a significant increase of hypoglycemia's risk. However, innovative options, such as fixed ratio combinations of glucagon-like peptide 1 receptor agonists (GLP-1RA) and basal insulin, minimize weight gain and hypoglycemia risks and allow a greater proportion of patients to achieve individual glycemic control goals without compromising safety parameters. This review includes a description of the randomized clinical trials, as well as the results of real clinical practice of the use of two currently existing fixed ration combinations of GLP-1RA and basal insulin - iDegLira and iGlarLixi.

[Evolution of insulin therapy: past, present, future].

2021 marks the 100th anniversary of the discovery of insulin, an event that forever changed the lives of people with diabetes mellitus. At present patients around the world experience the miracle of insulin therapy every day. A disease that used to kill children and teenagers in 2 years in 1920 has become a disease that can be controlled with a possibility to lead a long productive life. Over the past century, the great discovery of Banting, Best and Collip has forever changed the world and saved millions of lives. This review is devoted to the history of the development of insulin and its further improvement: from the moment of discovery to the present days. Various generations of insulin are considered: from animals to modern ultrashort and basal analogues. The article ends with a brief review of current trends in the development of new delivery methods and the development of new insulin molecules. Over the past century, insulin therapy has come a long way, which has significantly improved the quality of life of our patients. But research is actively continuing, including in the field of alternative methods of insulin delivery, which are more convenient for the patient, as well as in the development of «smart¼ molecules that will have a glucose-dependent effect.

[Characteristics of purchases of hypoglycemic agents in pharmacy retail sector in 2016-2020 years dynamics].

BACKGROUND: Procurement of medicines reflects the demand and frequency of prescribing certain drugs, which makes it possible to assess the quality of medical care and compliance with standards. The Russian pharmaceutical market is dynamically developing and expanding, therefore, the commercial sector of drug circulation is a significant part of it and should be studied along with public procurement. Given the significant number of patients diagnosed with diabetes mellitus (DM) in our country, we considered it appropriate and interesting to analyze the structure and volume of turnover of antidiabetic drugs in the retail trade over five years. AIM: to assess the dynamics of the cost and sales volumes of hypoglycemic drugs in the commercial sector for 2019-2020 compared to 2016. MATERIALS AND METHODS: The analysis was made on the basis of the data of antidiabetic drugs purchases in Russian pharmacies in 2016 and 2019-2020, according to 95257 pharmacies data. RESULTS: In 2020, compared to 2016, we see a significant increase in the number of packages purchases (+14,952,897 rub.) and the purchases total amount (+9,377,975,722 rub.), in parallel with the increase in average price per box of the hypoglycemic drug +199, 57 rub. The average price for DPP4 decreased. The cost per pack of metformin remains one of the lowest, second only to glibenclamide and gliclazide. The most expensive drugs include GLP1 group representatives. Insulin purchases have halved, when budget for GLP1 have increased by 10 times, for SGLT2 by 9.5 times, and for DPP4 by 2.1 times. In 2020, metformin gliclazide, a combination of glibencladimide with metformin, glibenclamide and vildgaliptin remain leaders in the number of purchased packages. The purchase leaders in terms of budget share are: metformin, gliclazide, liraglutide, vildagliptin and dapagliflozinCONCLUSION: There are positive trends in the demand for more effective innovative hypoglycemic drugs, however, the affordability of drugs still dominates over the feasibility of their clinical use, and a high percentage of drug turnover in the commercial sector might indicates insufficient funding for drug provision for patients with diabetes mellitus.

[Study of the effect of Unifuzol on cognitive impairment and damage to the hippocampus and cerebral cortex during course administration to rats with bilateral stenosis of the common carotid arteries, causing chronic circulatory failure]. / Vliyanie preparata Unifuzol na sostoyanie kognitivnykh funktsii v usloviyakh eksperimental'nogo khronicheskogo narusheniya mozgovogo krovoobrashcheniya.

OBJECTIVE: To study the effect of Unifuzol (L-arginine sodium succinate) on cognitive impairment, cerebral blood flow, and damage to the tissues of the hippocampus and cerebral cortex during a 10-day course of administration to rats with chronic cerebral ischemia (CCI) caused by bilateral stenosis of the common carotid arteries (CCA). MATERIAL AND METHODS: The study was conducted on male rats with CCI caused by bilateral stenosis of the CCA by 60%. 40 days after surgery, rats received Unifusol (21, 42 and 84 ml/kg), nicergoline (10 mg/kg), citicoline (500 mg/kg) or placebo (0.9% NaCl) for 10 days. Next, cognitive impairments were assessed in the Morris Water Maze and the New Object Recognition (NOR) test, as well as the level of motor and exploratory activity in the Open Field test. The level of cerebral blood flow was determined immediately after the CCA stenosis and at the end of the experiment. Animals were euthanized in a CO2 incubator, after which the brain was removed and subjected to morphometric analysis. RESULTS: In animals that were modeled with CCA stenosis, pronounced behavioral and cognitive impairments occurred as a result of a decrease in blood flow in the vessels of the brain and subsequent changes in the tissues of the hippocampus and the cerebral cortex. Intravenous course administration of Unifuzol at doses of 42 and 84 ml/kg to animals with CCI was comparable in efficiency to nicergoline and citicoline, which was expressed in greater preservation of the cognitive abilities of animals in the Morris Water Maze and NOR tests. In the Open Field test, animals injected with Unifusol at doses of 42 and 84 ml/kg performed more acts of motor and exploratory activity than animals from the placebo group, and had a higher level of cerebral blood flow (compared to animals that were injected with citicoline). Based on the results of a morphological study, it was found that the most significant neuroprotective effect was provided by nicergoline and Unifuzol (at doses of 42 and 84 ml/kg). CONCLUSION: Unifuzol at a course of administration at doses of 42 and 84 ml/kg, comparable to the reference drugs nicergoline and citicoline, reduces the severity of psychoneurological deficit in animals with CCI, comparable to them improves the microcirculation of brain tissues, preventing damage to brain tissues.

[Antioxidant effect of cortexin, cerebrolysin and actovegin in rats with chronic cerebrovascular insufficiency]. / Antioksidantnoe deistvie Korteksina, Tserebrolizina i Aktovegina u zhivotnykh s khronicheskoi ishemiei golovnogo mozga.

OBJECTIVE: To compare the antioxidant effects of cortexin, cerebrolysin and actovegin in rats with chronic brain ischemia. MATERIAL AND METHODS: Chronic brain ischemia was modeled in male rats by 50% stenosis of the common carotid arteries. Forty days after surgery, the animals received 2 ten-day courses of therapy, separated by a break of 10 days. Placebo, cortexin (0.3, 1 and 3 mg/kg), cerebrolysin (0.8, 2.5 and 7.5 ml/kg) and actovegin (5 ml/kg) were administered to animals as treatment. The concentration of malondialdehyde (MDA) in the homogenates was determined by the reaction with thiobarbituric acid, the concentration of reduced glutathione was determined by the reduction reaction of 5.5-dithiobis- (2-nitrobenzoic acid); determination of catalase activity, as well as the content of lactate and pyruvate, by commercially available reagent kits. The activity of superoxide dismutase (SOD) was determined by the photometric method based on an assessment of the degree of inhibition of the epinephrine oxidation reaction. All reactions were carried out in triplicates. RESULTS: Modeling of chronic brain ischemia led to the statistically significant decrease in the content of lactate and pyruvate (p<0.001, when compared with the control group), which was not accompanied by a significant decrease in their ratio (p>0.05), as well as to the decrease in SOD, catalase activity, restored glutathione and increase in MDA concentrations. Compared with the control group, in the groups that received cortexin at a dose of 3 mg/kg/day, cerebrolysin at a dose of 7.5 ml/kg/day and actovegin at a dose of 5 ml/kg/day, there were an increase in the content of lactate and pyruvate (without a significant change in their ratio), restoration of glutathione levels and the activity of SOD and, to a lesser extent, catalase, combined with a decrease in the concentration of MDA. CONCLUSION: Course administration of cortexin (3 mg/kg), cerebrolysin (7.5 ml/kg) and, to a lesser extent, actovegin (5 ml/kg) has a positive effect on the state of the antioxidant system of the brain in rats with chronic brain ischemia.

[Comparative study of protective effects of Cortexin, Cerebrolysin and Actovegin on memory impairment, cerebral circulation and morphological changes in the hippocampus of rats with chronic brain ischemia]. / Sravnitel'noe izuchenie vliyaniya Korteksina, Tserebrolizina i Aktovegina na sostoyanie pamyati, mozgovoe krovoobrashchenie i strukturu gippokampa u krys s khronicheskim narusheniem mozgovogo krovoobrashcheniya.

OBJECTIVE: To compare the effects of cortexin, cerebrolysin and actovegin on memory impairment, cerebral circulation and morphological changes in the hippocampus of rats with chronic brain ischemia. MATERIAL AND METHODS: The study was conducted using male rats with chronic brain ischemia caused by stenosis of the common carotid arteries by 50%. Animals received cortexin (0,3; 1 or 3 mg/kg), cerebrolysin (0,8; 2,5 or 7,5 ml/kg) and actovegin (5 ml/kg) in two 10-day courses with 10 days of treatment break. The severity of cognitive impairment was evaluated using the Morris water maze, passive and active avoidance tests. Cerebral circulation using laser flowmetry and brain hippocampus structures were studied in the end of treatment. RESULTS: Cognitive impairment in animals with chronic brain ischemia was accompanied by the development of pathological changes in the CA1 and CA4 regions of the hippocampus. Administration of cortexin (1 and 3 mg/kg) and cerebrolysin (2.5 and 7.5 ml/kg) to rats with chronic brain ischemia had almost no effect on cerebral blood flow, but contributed to the improvement in memory formation and retrieval processes in the Morris water maze. The treatment effect was comparable for both drugs and persisted after 10 days of treatment break. Morphological assessment showed a decrease in the severity of pathological changes in the hippocampal regions. CONCLUSION: The course-administration of cortexin and cerebrolysin lead to a decrease in the severity of memory impairment and pathomorphological changes in the hippocampus in rats with chronic brain ischemia.

Expression of Beclin-1 and LAMP-2 in Rat Hippocampus under Conditions of Simulated Gravity Overload in the Caudocranial Vector.

Structural changes in the rat hippocampus in response to chronic cerebrovascular disorders induced by gravity exposure in the caudocranial vector were studied. Qualitative and quantitative morphological analysis detected significant cytoarchitectonic changes in the pyramidal layer: spongiosis, manifest pericellular and perivascular edema, and a drastic increase in the counts of pyramidal neurons with signs of impairment in all hippocampal zones. The density of perikarya in the pyramidal layer decreased. Immunohistochemical study detected high expression of Beclin-1 in CA1 field. High expression of LAMP-2 was detected in CA4 field. Field CA2 was characterized by the maximum counts of damaged cells and high expression of Beclin-1 and LAMP-2.

[Focal cerebral ischemia in rats with estrogen deficiency and endothelial dysfunction]. / Fokal'naia ishemiia golovnogo mozga u krys na fone nedostatochnosti éstrogenov i éndotelial'noi disfunktsii.

AIM: To assess an effect of ovariectomy (OE) on the cerebral blood flow, endothelium-dependent vasodilation, neurological, cognitive and locomotor deficit as markers of brain damage after focal ischemia in rats. MATERIAL AND METHODS: The study was conducted in 48 female Wistar rats. Ovariectomy was performed with ovaries and uterine body extirpation, cerebral ischemia was performed by middle cerebral artery occlusion (MCAO) in rats. To assess brain damage, Combs and Garcia scores, 'open field' test (OFT), 'extrapolatory escape test' (EET), 'passive avoidance test' (PAT), 'beam-walking test' were used. Cerebral blood flow was measured using ultrasonic flowmetry. RESULTS AND CONCLUSION: After 7 days of MCAO, the cerebral blood flow in ovarioectomized animals was reduced by 20% compared to sham-ovariectomized animals. Ovariectomized animals with MCAO showed a three-fold endothelium-dependent vasodilation reduction (the reaction of cerebral vessels to the introduction of acetylcholine and N-L-arginine), indicating the presence of severe endothelial dysfunction. In ovarioectomized animals, the cerebral blood flow was reduced by 34% compared to sham-operated animals. MCAO and OE taken together resulted in more than 2-fold increase in neurological, motor disturbances, 3-fold decrease in motor activity of the animals in the OP test. Focal ischemia in ovarioectomized animals with endothelial dysfunction led to memory decrease by 1/5 fold in PAT and by 2-fold in EET.

[Behavioral phenotyping in rats during the experimental modeling of chronic cerebral circulation disorder]. / Povedencheskoe fenotipirovanie krys pri éksperimental'nom modelirovanii khronicheskogo narusheniia mozgovogo krovoobrashcheniia.

AIM: To describe motor, adaptive and cognitive disorders in rats with chronic cerebral circulatory deficiency caused by partial stenosis of the common carotid arteries (CCA). MATERIAL AND METHODS: A study was performed on 20 white outbred male rats. This manipulation led to 40-45% and 50-60% reduction of blood flow in CCA and in the brain, respectively. Twenty days after operation, animal's condition was assessed in the following tests: open field test, rotarod performance test, marble burying test and novel object recognition. RESULTS AND CONCLUSION: After 20 days of experimental CCA stenosis, animals demonstrated several signs of neuropsychiatric deficiency including coordination disorders, a decrease in locomotor activity as well as in explorative and protective behavior. The model of CCA partial stenosis could be used during further studies of the pathophysiology and pharmacology of chronic cerebral circulatory deficiency.

[HYPOLIPIDEMIC, ANTIOXIDANT, AND ENDOTHELIAL PROTECTIVE EFFECT OF COMPOUND ZB-16 (NOVEL GPR119 RECEPTOR AGONIST) IN RATS WITH EXPERIMENTAL TYPE 2 DIABETES.]

The effect of compound ZB-16 (a new GPR1 19 receptor agonist) after two-week administration on the endothelial function, glucose and lipid metabolism (total cholesterol, LDL, HDL and triglycerides), lipid peroxidation, and antioxidant system status in rats with experimental type-2 diabetes mellitus (T2DM) has been studied. It was found that the untreated control group of animals exhibited, in addition to sustained hyperglycemia, a decrease in endothelium-dependent vaso- dilation and antioxidant system activity, and increase in the content of LDL and the dyslipidemic index. Administration of ZB-16 (1 mg/kg, p.o.) in rats with T2DM model resulted in reduction of the endothelial dysfunction (improved endothelium-dependent vasodilation by 83% as compared to the control group, p < 0.05). ZB-16 also produced a moderate antioxidant effect of reducing the content of TBA-active products (by 30% as compared to the untreated control, p <0.05) and favored normalization of lipid metabolism indicators.

[Cerebroprotective activity of metformin, gosogliptin, citicoline and a novel GPR119 agonist in cerebral ischemia under experimental diabetes mellitus]. / Sravnitel'naia tserebroprotektivnaia aktivnost' metformina, gosogliptina, tsitikolina i novogo agonista GPR119 pri éksperimental'noi ishemii golovnogo mozga na fone sakharnogo diabeta.

Hypoglycemic agents of some groups: sodium-glucose cotransporter type 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists reduce the risk and/or severity of cardiovascular diseases. Studies of such properties are currently focused on metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors. Agonists of GPR119 receptor, increasing the secretion of GLP-1 and insulin, are also actively studied as hypoglycemic drugs with endothelial and cerebroprotective potential. AIM: To evaluate the cerebroprotective activity of metformin, gosogliptin, citicoline and an agonist of GPR119 (ZB-16) in middle cerebral artery occlusion (MCAO) in animals with 4-week streptozotocin-nicotinamide-induced diabetes. MATERIAL AND METHODS: A study included 73 male rats. Hypoglycemic agents and ZB-16 were administered on the first day of diabetes and citicoline was administered after MCAO. Cerebroprotective effect was evaluated using Garcia, Combs and D'Alecy score test, 'Rotarod' and 'open field' test, as well as the infarct volume and severity of brain edema measurement. RESULTS AND CONCLUSION: Preventive administration of metformin resulted in the pronounced hypoglycemic activity without a significant cerebroprotective effect in subsequent brain ischemia modelling. Administration of substances with incretin activity (gosogliptin and, in particular, ZB-16) in addition to the hypoglycemic action promoted a significant reduction of infarct volume, brain edema and severity of neurologic deficit of the surviving animals. At the same time, the introduction of citicoline without proper glycemic control didn't reduce the brain ischemia severity.

[COMPARATIVE CEREBROPROTECTIVE EFFECT OF PREVENTIVE ADMINISTRATION OF MAGNESIUM HYDROXYBUTYRATE VERSUS MAGNESIUM SULFATE AND CAVINTON IN RATS WITH COMMON CAROTID ARTERY OCCLUSION].

Dose-dependent cerebroprotective effect of magnesium hydroxybutyrate (MHB) on common carotid artery occlusion model in rats was established. Administration of 150 mg/kg MHB led to significant decrease in animal mortality (up to 9.3 times) in comparison to control (p < 0.05). This MHB dose also produced significant decrease of neurological deficit on the McGraw scale in comparison to control and magnesium sulfate (50% and 20%, respectively). The MHB treated animals also showed improved locomotor and exploratory performance in the open-field test and retained memory performance in the passive avoidance test and extrapolation escape task test. The administration of 150 mg/kg MHB produced three-fold (p < 0.05) decrease of brain edema in animals with cerebral blood flow impairment in comparison to animals treated with magnesium sulfate and cavinton.

[COMPARATIVE MORPHOFUNCTIONAL CHARACTERISTICS OF ADULT AND OLD RAT VENTRAL HIPPOCAMPUS TO COMBINED STRESS INFLUENCE].

Animals were subjected to seven days combined stress in a special chamber (6 isolated compartments of equal area) with removable multi-modal stressors (noise, vibration, pulsating bright light) every 5 minutes on the stochastic scheme with restraint and temperature rise in the chamber during 30-minute stressing time sessions. After exposure to combined stress in the ventral hippocampus of old rats (24 months) compared with adult animals (12 months) following changes were revealed: marked dystrophic changes and increased inducible nitric oxide synthase expression in pyramidal neurons of CA3 field, signs of impaired hemodynamic disorders in the microvasculature, perivascular edema, decreased endothelial nitric oxide synthase expression in microvascular endothelial cells, as well as decreased expression of serine racemase in the neuropil of the radial layer of CA1 field.

NEUROPROTECTIVE ACTION OF PHENIBUT AND NEUROGLUTAM IN EXPERIMENTAL CEREBRAL ISCHEMIA ON THE BACKGROUND OF ALTERED IMMUNOREACTIVITY.

Cerebroprotective activity of phenyl derivatives of GABA (phenibut, 25 mg/kg) and L-glutamic acid (neuroglutam, 26 mg/kg) in rats with cerebral ischemia was studied on the background of intact and altered immunoreactivity. Tested compounds were administered intraperitoneally for 7 days after two phase ligation of common carotid arteries (second artery was ligated 3 days after ligation of the first artery). Immunosuppression caused by cyclosporin (daily dose 5 mg/kg, p.o., for 13 days) worsened brain ischemia outcome, as manifested by increased mortality, more severe neurological marker score, increased levels of brain damage markers (NSE and MBP) in the blood serum, decrease in muscle strength and locomotor activity, and impairment of orientation and research activity as compared to animals with brain ischemia and intact immunity. Activation of immune system was caused by lipopolysaccharide (10 mg/kg, i.p., 7 injections every second day). Upon activation of the immune system, brain ischemia produced lower mortality, while the survived rats exhibited more favorable outcome of ischemia than animals with suppression of immune system: lover neurological marker score, lower blood serum NSE and MBP levels (-35% on average,p < 0.05), and much higher level of performance in motor coordination, muscular strength, and locomotor activity (+90% on average, p < 0.05). The state of immune system significantly influenced the neuroprotective activity of drugs tested. Neuroglutam administration produced positive effect both in animals with intact immunity and on the background of altered immunoreactivity. However, most positive outcome after neuroglutam administration in ischemic rats was observed in animals with suppression of immune system, with significant increase in the cerebral blood flow level (+56%), decrease in NSE and MBP blood serum levels (57 and 76%, respectively) after 7-day treatment as compared to the control group. The therapeutic potential of phenibut was somewhat lower than that of neuroglutam, and it was more pronounced in rats with activated immune system, whereas the drug effectiveness in rats with suppressed immune system was less pronounced.

[The influence of the immunity activation and suppression on the outcome of brain ischemia]. / Ishemiia golovnogo mozga na fone podavleniia i aktivatsii immuniteta.

AIM: To explore the influence of the immunity activation and suppression on the outcome of brain ischemia in experimental animals. MATERIAL AND METHODS: Brain ischemia has been modulated by irreversible staged bilateral common carotid arteries occlusion. Suppression of the immune system has been conducted by administration of cyclosporin A (5 mg/kg, per os). Activation of the immune system has been conducted by administration of lipopolysaccharide (10 mkg/kg, i.p.). RESULTS: Authors have established that in animals with immunosuppression there is an increase in the concentration of the neuron specific proteins in blood serum (NSE and MBP), mortality (by 20%) and severity of neurological deficit (by 33%). Rats with immunosuppression have reduced general locomotor activity (by 44%), exploratory behavior in the Open Field Test (by 43%) and decrease in the motor activity in the Rotarod Test (by 19%) compared to the group of rats with brain ischemia and intact immune systems. During the immunity activation after brain ischemia injury, the decrease in NSE and MBP levels, mortality (by 15%) and severity of neurological deficit (by 13%) as well as higher concentrations of neurotrophins BDNF and NGF and higher general locomotor activity of animals (by 34%) and physical endurance (by 55%) in the Open Field and Rotarod Tests, respectively, were observed. CONCLUSION: Immunosupression negatively affected the outcome of brain ischemia.

[GLIATILIN CORRECTION OF WORKING AND REFERENCE SPATIAL MEMORY IMPAIRMENT IN AGED RATS].

This work was aimed at evaluating the influence of gliatilin administration on the spatial memory in aged rats. Cognitive function and spatial memory in animals was evaluated using radial (8-beam) maze test. Errors of working spatial memory and reference memory were used as indicators of impaired cognitive function. It was found that aged (24-month) rats compared with younger (6-months) age group exhibited cognitive impairment, as manifested by deterioration of short- and long-term memory processes. Course administration of gliatilin in rats of the older age group at a dose of 100 mg/kg resulted in significant improvement of the working and reference spatial memory in aged rats.

Neuroprotective and Antioxidant Effects of Neuroglutam in Cerebral Ischemia.

We studied in vitro and in vivo neuroprotective and antioxidant properties of neuroglutam, a new glutamic acid derivative. In experiments on immortalized mouse hippocampal cell line HT22, neuroglutam exhibited a neuroprotective effect in the model of oxidative stress after its introduction, both before and after H2O2. In vivo study on animals treated with neuroglutam against the background of cerebral ischemia modeled by irreversible occlusion of the common carotid arteries showed that plasma level of TBA-active products was significantly lower and activities of cell antioxidant enzymes (superoxide dismutase and catalase) were higher than in control animals receiving saline under the same conditions.

[GPR119 Receptor Agonists: Characteristics, Physiological Role, Prospects of Use in the Treatment of Diabetes Mellitus Type 2 and Metabolic Syndrome].

Last decade GPR119 receptor attracted great attention of many researchers groups worldwide. This receptor is expressed in enteroendocrine L- and K-intestinal cells and pancreas beta cells. First endogenous ligands for GPR119 was found in 2005: fatty acid metabolites, some phospholipids and fatty acid amides derivatives. GPR119 receptor is involved in the glucose metabolism regulation: glucose-dependent insulin secretion, glucose-independent incretin secretion, appetite control, gastric emptying, as well as beta cell proliferation. Thus, GPR119 is a "sensor" of some fatty acid derivatives and-GPR119 is a promising new pharmacological target for the treatment of type 2 diabetes.