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Intestinal electrical stimulation (IES) has been proposed for treating diabetes; however, its parameters need to be further systematically optimized. This study aimed to optimize the parameters of IES and investigate its possible mechanisms involving glucagon-like peptide-1 (GLP-1) in diabetic rats.Thirty-six high-fat diet-induced diabetic rats were chronically implanted with a pair of bipolar electrodes at the duodenum for IES. The oral glucose tolerance test (OGTT) was performed in a number of sessions with IES using different parameters and biphasic charge-balanced waveforms to derive the best values for train on-time, pulse frequency, and pulse width. Incretin hormones such as GLP-1 were assessed and the GLP-1 antagonist Exendin 9-39 was used to assess the role of GLP-1 in the ameliorating effect of IES on hyperglycemia.The most effective IES parameters in reducing blood glucose (BG) during the OGTT were derived: 1.2 sec on, 0.3 sec off, 80 Hz, 3 msec. IES with these parameters reduced BG level by at least 29% from 15 min to 180 min (p 0.05 for all points, N = 10). IES with these stimulation parameters increased plasma GLP-1 level at 30 min, 60 min, 90 min and gastric inhibitory peptide (GIP) level at 30 min (N = 8). Exendin 9-39 blocked the inhibitory effect of IES on BG (p 0.05, IES + Exendin 9-39 vs sham-IES, N = 8).IES with the most effective parameters derived in this study improves hyperglycemia in diabetic rats. The ameliorating effect of IES on hyperglycemia is attributed to the enhanced release of GLP-1. IES has great potential for treating diabetes.

Patients with type 2 diabetes mellitus (T2DM) are at increased risk for severe coronavirus disease 2019 (COVID-19) and related mortality. Glucagon-like peptide-1 receptor agonists (GLP-1-RAs) have significant cardiovascular and renal benefits for patients with T2DM and related comorbidities. Their anti-inflammatory properties could be beneficial in these patients. This work provides less-biased estimates regarding the risk for respiratory tract infections and acute respiratory distress syndrome by performing the first significant meta-analysis of cardiovascular outcome trials in the literature. Notably, GLP-1-RAs do not seem to increase the risk for respiratory tract infection, pneumonia, or acute respiratory distress syndrome in patients with T2DM and cardiovascular comorbidities.

Obesity and associated comorbidities reach epidemic proportions nowadays. Several treatment strategies exist, but bariatric surgery has the only longstanding effects. Since a few years, there is increasing interest in the effects of gastro-intestinal hormones, in particular Glucagon-Like Peptide-1 (GLP-1) on the remission of Type 2 Diabetes (T2DM) and its effects on cardiac cardiovascular morbidity, cardiac remodelling and mortality. In the past years several high quality multicentre randomised controlled trials were developed to assess the effects of GLP-1 receptor agonist therapy on cardiovascular morbidity and mortality. Most of the trials were designed and powered as non-inferiority trials to demonstrate cardiovascular safety. The majority of these trials show a reduction in cardiovascular morbidity in patients with T2DM. Some follow-up studies indicate potential beneficial effects of GLP-1 receptor agonists on cardiovascular function in patients with heart failure, however the results are contradictory and we are in need of long-term studies to make firm conclusions about the pleiotropic properties of incretin-based therapies. However it seems that GLP-1 receptor agonists have different effects than the increased GLP-1 production after bariatric surgery on cardiovascular remodelling. One of the hypothesis is that the blood concentrations of GLP-1 receptor agonists are three times higher compared to GLP-1 increase after bariatric and metabolic surgery. The purpose of this narrative review is to summarise the effects of GLP-1 on cardiovascular morbidity, mortality and remodelling due to medication but also due to bariatric and metabolic surgery. The second objective is to explain the possible differences in effects of GLP-1 agonists and bariatric and metabolic surgery.

Understanding of gustatory coding helps to predict, and perhaps even modulate the ingestive decision circuitry, especially when eating behaviour becomes dysfunctional. Preclinical research demonstrated that glucagon like peptide 1 (GLP-1) is locally synthesized in taste bud cells in the tongue and that GLP-1 receptor exists on the gustatory nerves in close proximity to GLP-1 containing taste bud cells. In humans, the tongue has not yet been addressed as clinically relevant target for GLP-1 based therapies. The primary aim of the current review was to elaborate on the role of GLP- 1 in mammalian gustatory system, in particular in the perception of sweet. Secondly, we aimed to explore what modulates gustatory coding and whether the GLP-1 based therapies might be involved in regulation of taste perception. We performed a series of PubMed, Medline and Embase databases systemic searches. The Population-Intervention-Comparison-Outcome (PICO) framework was used to identify interventional studies. Based on the available data, GLP-1 is specifically involved in the perception of sweet. Aging, diabetes and obesity are characterized by diminished taste and sweet perception. Calorie restriction and bariatric surgery are associated with a diminished appreciation of sweet food. GLP-1 receptor agonists (RAs) modulate food preference, yet its modulatory potential in gustatory coding is currently unknown. Future studies should explore whether GLP-1 RAs modulate taste perception to the extent that changes of food preference and consumption ensue.

Effects of pancreatectomy on glucose tolerance have not been clarified, and evidence regarding the difference in postoperative glucose tolerance between pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) is lacking.This prospective, single-center observational study analyzed 40 patients undergoing PD and 29 patients undergoing DP (Clinical trial registry number UMIN000008122). Glucose tolerance, including insulin secretion (Δ C-peptide immunoreactivity, ΔCPR) and insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR) were assessed before and 1 month after pancreatectomy using the oral glucose tolerance test (OGTT) and glucagon stimulation test. We assessed long-term hemoglobin A1c (HbA1c) levels in patients, with a follow-up time of 3 years.Percentages of patients diagnosed with abnormal OGTT decreased after PD (from 12 [30%] to 7 [17.5%] of 40 patients, p = 0.096); however, they increased after DP (from 4 [13.8%] to 8 [27.6%] of 29 patients, p = 0.103), although the changes were not statistically significant. ΔCPR decreased after both PD (from 3.2 to 1.0 ng/mL, p0.001) and DP (from 3.3 to 1.8 ng/mL, p0.001). HOMA-IR decreased after PD (from 1.10 to 0.68, p 0.001), but did not change after DP (1.10 and 1.07, p = 0.42). Median HbA1c level was higher after DP than after PD for up to 3 years, but the differences were not statistically significant.In comparisons of pre- and 1 month post-pancreatectomy data, glucose tolerance showed improvement after PD, whereas it worsened after DP. Insulin secretion decreased after both PD and DP. Insulin resistance improved after PD, but did not change after DP. Further studies are warranted to clarify mechanisms of improved insulin resistance after PD.

Peripheral glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) are secreted from enteroendocrine cells, and their plasma concentrations increase in response to eating. While the satiating effect of gut-derived CCK on food intake control is well documented, the effect of peripheral GLP-1 is less clear. There is evidence that native GLP-1 can inhibit food intake only in the fed state but not in the fasting state. We therefore hypothesised that other gut peptides released during a meal might influence the subsequent effect of endogenous GLP-1 and investigated whether CCK could do so. We found that intraperitoneal injection of CCK in food-restricted mice inhibited food intake during the first 30 min segment of a one-hour session of ad libitum chow intake and that mice compensated by increasing their intake during the second half of the session. Importantly, this compensatory behaviour was abolished by an intraperitoneal injection of GLP-1 administered following an intraperitoneal injection of CCK and prior to the one-hour session. In vivo activation of the FFA1 receptor with orally administered TAK875 increased plasma CCK concentration and, consistent with the effect of exogenous CCK, we found that prior oral administration of TAK875 increased the eating inhibitory effect of peripherally administered GLP-1. To examine the role of the vagus nerve in this effect, we utilised a saporin-based lesioning procedure to selectively ablate the CCK receptor-expressing gastrointestinal vagal afferent neurones (VANs). We found that the combined anorectic effect of TAK875 and GLP-1 was significantly attenuated in the absence of CCK receptor expressing VANs. Taken together, our results indicate that endogenous CCK interacts with GLP-1 to promote satiation and that activation of the FFA1 receptor can initiate this interaction by stimulating the release of CCK. This article is protected by copyright. All rights reserved.

Jabuticaba is a Brazilian berry rich in polyphenols, which may exert beneficial effects on metabolic diseases. This randomised crossover study aimed to determine the effects of jabuticaba juice (250 ml in a portion) on postprandial response. Sixteen healthy subjects (eleven women; five men; 28·4 (sd 3·8) years old; BMI 21·7 (sd 2·3) kg/m−2) consumed two test products after fasting overnight in a randomised controlled crossover design. Each test product portion had a similar composition of sugar components: 250 ml water with glucose, fructose, coloured with artificial non-energetic food colourings (placebo), and 250 ml of jabuticaba juice. Beverages were administered immediately before a carbohydrate meal. Blood samples were collected at 0, 15, 30, 45, 60, 90 and 120 min after each test product to analyse the concentrations of glucose, insulin, C-peptide, antioxidant capacity, plasma glucagon-like peptide-1 (GLP-1) and appetite sensations. Compared with the placebo, the intake of jabuticaba juice resulted in a higher GLP-1 response as the AUC and peaking at 60 min. Jabuticaba juice also resulted in higher antioxidant capacity. Postprandial glucose, insulin, C-peptide levels and appetite sensations were not significantly different between tests. In conclusion, 250 ml of jabuticaba juice before a carbohydrate meal was able to improve the antioxidant status and GLP-1 concentrations in healthy subjects.

Prevention of cardiovascular events and regression of atherosclerotic changes are the primary aims of preventive cardiovascular medicine. Arterial thrombosis is caused by endothelial dysfunction, which disrupts vascular haemostasis. Glucagon-like peptide 1 (GLP-1) receptor agonists have been initially used as glucose lowering agents, but over time have been used for other indications due to their cardiorenal benefit, as well as their benefit in the regression of atherosclerosis process. The aim of this paper is to present the benefits of GLP-1 receptor agonists in the prevention of atherosclerotic changes, in the preservation of brain vascular function, and to show the possible role in the treatment of neurodegenerative diseases.

Increasing evidence shows a close relationship between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). Recently, glucagon-like peptide-1 (GLP-1), a gut incretin hormone, has become a well-established treatment for T2DM and is likely to be involved in treating cognitive impairment. In this mini review, the similarities between AD and T2DM are summarised with the main focus on GLP-1-based therapeutics in AD.

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is known to lower glucose levels, suppress glucagon secretion, and slow gastric emptying. These properties make GLP-1 an ideal target in treating type 2 diabetes mellitus (T2DM). There are many FDA-approved GLP-1 agonists on the market today, several of which have demonstrated benefit beyond improving glycemic control. Given the beneficial effects of GLP-1 agonists in patients with T2DM, new drugs are in development that combine the mechanism of action of GLP-1 receptor agonism with novel mechanisms and with drugs that promote GLP-1 secretion. These agents are designed to improve glycemic control and target greater body weight reduction. This article discusses new GLP-1 drugs in the pipeline for the treatment of T2DM.

Glucagon-like peptide 1 (GLP-1) and its agonists exert anorexigenic effect at least partly via acting on GLP-1 receptors (GLP-1R) in the arcuate nucleus (ARC). While the anorexigenic, proopiomelanocortin (POMC) neurons of the ARC were shown previously to express GLP-1R, the putative GLP-1R-content of the orexigenic, neuropeptide Y (NPY) neurons remained so far undetected. As GLP-1R is abundant in the ventromedial ARC, where NPY neurons are located; here, we address the possibility that GLP-1 can act directly on the orexigenic NPY system via GLP-1R. Double-labeling immunocytochemistry and in situ hybridization were performed on tissues of adult male mice to detect GLP-1R in NPY neurons. In double-immunolabeled preparations, GLP-1R-immunoreactivity was observed in NPY neurons and in axons ensheathing the majority of NPY neurons. Ultrastructural studies confirmed that GLP-1R-immunoreactivity is associated with the outer membrane of NPY perikarya as well as with axons forming symmetric type, inhibitory synapses on NPY-containing neurons. Double-labeling in situ hybridization experiments demonstrated the expression of GLP-1R mRNA in approximately 20% of NPY mRNA-containing neurons of the ARC. In summary, our data demonstrate the presence of GLP-1R protein and mRNA in NPY neurons of ARC and also reveal the innervation of NPY neurons by GLP-1R-containing inhibitory neurons. These observations suggest that GLP-1 signaling can influence NPY neurons both directly and indirectly. Furthermore, GLP-1 signaling on energy homeostasis appears to involve both direct and indirect effects of GLP-1 on the orexigenic NPY neurons, in addition to the previously known effects via the anorexigenic POMC neuronal system.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are innovative drugs that effectively reduce glycemic levels and overweight in patients with type 2 diabetes mellitus (T2DM). However, the criteria for predicting the hypoglycemic effect of this group of drugs have not been practically defined.To assess the factors contributing to the achievement the glycemia normalization in patients with diabetes mellitus and obesity by adding to antihyperglycemic therapy (AT) a drug from the GLP-1 RA group liraglutide 3.0 mg per day.A single-center, prospective, non-randomized study was provided. The objects of the study were patients with T2DM and obesity (n=22). Liraglutide 3.0 mg per day was added to the current AT of patients. Initially, the parameters of carbohydrate metabolism, hormones of the incretin system on an empty stomach and during the mixed-meal test, insulin resistance using the euglycemic hyperinsulinemic clamp test, and body composition were studied. After 9 months of therapy, all studies were repeated and a search for possible predictors of the carbohydrate metabolism normalization was made.The body mass index of patients decreased from 42.4 [37.7; 45.0] to 35.9 [33.0; 40.9] kg/m2. Fasting blood glucose and glycated hemoglobin levels decreased from 9.02 [7.40; 11.37] mmol/L and 7.85 [7.43; 8.65]% up to 5.90 [5.12; 6.18] mmol/L and 6.40 [5.90; 6.60]%, respectively. 14 (63.6%) patients reached normoglycemia. Insulin resistance according to the clamp test did not change over the study. Basal concentrations of oxyntomodulin, glycentin and the area under the GLP-1, oxyntomodulin, glycentin curve significantly decreased 9 months after liraglutide administration. The prognostic marker of the achievement of normoglycemia during therapy with liraglutide 3.0 mg/day is the level of endogenous GLP-15.5 pmol/L before the appointment of arGPP-1 therapy.The concentration of endogenous GLP-1 before the appointment of liraglutide therapy at a dose of 3.0 mg per day can be used for prediction the drug hypoglycemic effect and achieving normoglycemia possibility.Актуальность. Агонисты рецепторов глюкагоноподобного пептида-1 (арГПП-1) являются инновационными препаратами, эффективно снижающими уровень гликемии и избыточный вес у пациентов с сахарным диабетом 2-го типа (СД 2). Однако практически не определены критерии, позволяющие прогнозировать сахароснижающий эффект этой группы препаратов. Цель. Оценить факторы, способствующие достижению нормализации гликемии у пациентов с СД 2 и ожирением при добавлении к сахароснижающей терапии (СТ) препарата из группы арГПП-1 лираглутида 3,0 мг/сут. Материалы и методы. Проведено одноцентровое проспективное нерандомизированное исследование. Объектами исследования выступили пациенты с СД 2 и ожирением (n=22). К текущей СТ пациентов был добавлен лираглутид 3,0 мг/сут. Исходно исследованы показатели углеводного обмена, гормонов инкретиновой системы натощак и в течение теста со смешанной пищей, инсулинорезистентности с помощью эугликемического гиперинсулинемического клэмп-теста, композитного состава тела. Через 9 мес терапии повторены все исследования и проведен поиск возможных предикторов нормализации углеводного обмена. Результаты. Индекс массы тела пациентов снизился с 42,4 [37,7; 45,0] до 35,9 [33,0; 40,9] кг/м2. Уровни глюкозы крови натощак и гликированного гемоглобина снизились с 9,02 [7,40; 11,37] ммоль/л и 7,85 [7,43; 8,65]% до 5,90 [5,12; 6,18] ммоль/л и 6,40 [5,90; 6,60]% соответственно. Нормогликемии достигли 14 (63,6%) пациентов. Инсулинорезистентность, согласно клэмп-тесту, не изменилась на протяжении 9 мес исследования. Базальные концентрации оксинтомодулина, глицентина и площади под кривой ГПП-1, оксинтомодулина, глицентина значимо снизились через 9 мес после назначения лираглутида. Прогностическим маркером достижения нормогликемии при терапии лираглутидом 3,0 мг/сут является уровень эндогенного ГПП-15,5 пмоль/л до назначения терапии арГПП-1. Заключение. Концентрация эндогенного ГПП-1 до назначения терапии лираглутидом в дозе 3,0 мг/сут может быть использована для прогнозирования сахароснижающего эффекта препарата и возможности достижения нормогликемии.

Introduced less than two decades ago, glucagon-like peptide-1 receptor agonists rapidly reshaped the field of Type 2 diabetes mellitus (T2DM) care by providing glycaemic control in tandem with weight loss. However, FDA-approved GLP-1 receptor agonists are often accompanied by nausea and emesis and, in some lean T2DM patients, by undesired anorexia. Importantly, the hypophagic and emetic effects of GLP-1 receptor agonists are caused by activation of central GLP-1 receptors. This review summarizes two different approaches to mitigate the incidence and severity of nausea and emesis related to GLP-1 receptor agonists: conjugation with vitamin B(12), or related corrin ring-containing compounds (‘corrination’), and development of dual agonists of GLP-1 receptors with glucose-dependent insulinotropic polypeptide (GIP). Such approaches could lead to the generation of GLP-1 receptor agonists with improved therapeutic efficacy, thus decreasing treatment attrition, increasing patient compliance and extending treatment to a broader population of T2DM patients. The data reviewed show that it is possible to pharmacologically separate the emetic effects of GLP-1 receptor agonists from their glucoregulatory action.

Надано огляд літератури з питань терапії цукрового діабету 1-го і 2-го типу на основі інкретинового ефекту, про механізми дії, переваги й обмеження нового класу протидіабетичних препаратів — агоністів рецепторів глюкагоноподібного пептиду‑1 (ГПП‑1), про їх клінічне застосування в комбінації з інсуліном, що дозволяє нівелювати негативні ефекти останнього. Наводяться описи успішного клінічного застосування ліраглутиду в пацієнтів, що страждають на цукровий діабет 2-го типу, у випадках неефективно контрольованої глікемії натще, за відсутності компенсації глікемії високими дозами інсуліну й метформіну, а також при кардіоренальному синдромі.

The improvement of cognitive function following bariatric surgery has been highlighted, yet its underlying mechanisms remain elusive. Finding the improved brain glucose uptake of patients after Roux-en-Y gastric bypass (RYGB), duodenum-jejunum bypass (DJB), and sham surgery (Sham) were performed on obese and diabetic Wistar rats, and intracerebroventricular (ICV) injection of glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira), antagonist exendin-(9-39) (Exe-9), and the viral-mediated GLP-1 receptor (

Type 2 diabetes (T2D) is a multifaceted metabolic disorder associated with distinctive pathophysiological disturbances. One of the pathophysiological risk factors observed in T2D is dysregulation of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Both hormones stimulate insulin secretion by acting postprandially on pancreatic β-cell receptors. Oral glucose administration stimulates increased insulin secretion in comparison with isoglycemic intravenous glucose administration, a phenomenon known as the incretin effect. While the evidence for incretin defects in individuals with T2D is growing, the etiology behind this attenuated incretin effect in T2D is not clearly understood. Given their central role in T2D pathophysiology, incretins are promising targets for T2D therapeutics. The present review synthesizes the recent attempts to explain the biological importance of incretin hormones and explore potential pharmacological approaches that target the incretins.

The gut microbiome plays significant role in the function and integrity of the gastrointestinal tract. They also maintain immune homeostasis and host energy metabolism. The metabolic products of these intestinal microbes can alter carbohydrate metabolism, nutrient absorption and reduce appetite to promote healthy lifestyle. Intestinal disbiosis observed in metabolic disorders like obesity and diabetes. Restoration of dysbiosed gut microbiome through oral administration of probiotics that may have profound health effect in diabetes. In case of diabetes, reports postulated impaired level of incretin, therefore we explored the effect of oral administration of probiotic bacteria Lactobacillus casei NCDC 017 (LC017) and Bifidobacterium bifidum NCDC 231 (BB231) alone and in combination on secretion of incretin hormones such as glucagon like peptide-1 and glucose dependent insulinotropic polypeptide. Thirty six male Wistar rats were randomly divided into six groups and diabetes was induced by single dose of streptozotocin (50 mg/kg body weight) in experimental rats intraperitonially except a group of healthy rats. The diabetic rats were daily administered orally with single dose (~107cfu/ml) of LC017 and BB231 alone and in combination for 28 days. Also, one group of diabetic rats was treated with an anti-diabetic drug, acarbose (10mg/kg body weight) and used a standard control. The change in body weight, sucrose tolerance test, GLP-1, GIP level in serum and GLP-1 level in different part of intestine were observed. The results have shown reduction in body weight in diabetic rats as compared to non-diabetic rats but improved after treatment of probiotic bacteria. Administration of LC017 and BB231 significantly improved GLP-1 and GIP level which were initially impaired in diabetic rats and their combination significantly decreased glucose level in sucrose tolerance test. This study indicated that LC017 and BB231 have significant hypoglycaemic potential in diabetic rats by increasing GLP-1 and GIP level. These findings offered a base for the use of LC017 and BB231 for improvement and treatment of diabetes.

IntroductionDipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether vildagliptin protected endothelial function in diabetic rats and explored the involved mechanism.Material and methodsExperimental diabetic rats were obtained by feeding a high-fat diet and administering an intraperitoneal injection of streptozotocin. Rats were randomly divided into four groups: controls (CON), diabetes (DM), diabetes + low dose of vildagliptin (Lvil, 10 mg/kg/day), and diabetes + high dose of vildagliptin (Hvil, 20 mg/kg/day). The metabolic parameters, endothelial function, and whole miRNA expression were measured.ResultsAfter a 12-week treatment, vildagliptin-treated rats showed a significant reduction in blood glucose and blood lipid levels. Moreover, vildagliptin recovered aortic endothelial function in diabetic rats. We identified 31 miRNAs that were differentially expressed in the Hvil group compared with the diabetic group. Importantly, through miRNA target biological function and pathway analysis, we found that vildagliptin activated miR-190-5p to inhibit Ccl2 expression and inhibited miR-134-5p and miR-375-3p to increase Bdnf and Pdk1 expression in the aorta.ConclusionsOur present study indicates that vildagliptin can recover endothelial function in diabetic rats. Anti-inflammatory and anti-apoptosis mechanisms and endothelial moderation may be the intervention targets of vildagliptin to protect the cardiovascular system through miRNA regulation.

Loss or dysfunction of the pancreatic beta cells or insulin receptors leads to diabetes mellitus (DM). This usually occurs over many years; therefore, the development of methods for the timely detection and clinical intervention are vital to prevent the development of this disease. Glucagon-like peptide-1 receptor (GLP-1R) is the receptor of GLP-1, an incretin hormone that causes insulin secretion in a glucose-dependent manner. GLP-1R is highly expressed on the surface of pancreatic beta cells, providing a potential target for bioimaging. In this review, we provide an overview of various strategies, such as the development of GLP-1R agonists (e.g., exendin-4), and GLP-1 sequence modifications for GLP-1R targeting for the diagnosis and treatment of pancreatic beta cell disorders. We also discuss the challenges of targeting pancreatic beta cells and strategies to address such challenges.

Backgrounds and aims: The role of peroxisome proliferator activated receptor-γ (PPAR-γ) in neuronal apoptosis remains unclear. We aim to investigate the role of PPAR-γ in glucagon-like peptide-1 (GLP-1) alleviated neuronal apoptosis induced by carboxymethyl-lysine (CML). Materials and Methods: In vitro, PC12 cells were treated by CML/GLP-1. Moreover. the function of PPAR-γ was blocked by GW9662. In vivo, streptozotocin (STZ) was used to induce diabetic rats with neuronal apoptosis. The cognitive function of rats was observed by Morris water maze. Apoptosis was detected by TUNEL assay. Bcl2, Bax, PPAR-γ and receptor of GLP-1 (GLP-1R) were measured by western blotting or immunofluorescence. Results: In vitro experiment, CML triggered apoptosis, down-regulated GLP-1R and PPAR-γ. Moreover, GLP-1 not only alleviated the apoptosis, but also increased levels of PPAR-γ. GW9662 abolished the neuroprotective effect of GLP-1 on PC12 cells from apoptosis. Furthermore, GLP-1R promoter sequences were detected in the PPAR-γ antibody pulled mixture. GPL-1 levels decreased, while CML levels increased in diabetic rats, compared with control rats. Additionally, we observed elevated bax, decreased bcl2, GLP-1R and PPAR-γ in diabetic rats. Conclusions: GLP-1 could attenuate neuronal apoptosis induced by CML. Additionally, PPAR-γ involves in this process.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that facilitates insulin secretion and preserves β cell function. hypertriglyceridemia plays an important role in the pathogenesis of insulin resistance and T2DM. The purpose of this study was to measure fasting active GLP-1 levels in hypertriglyceridemia subjects and analyse the relationship between GLP-1 and insulin resistance. We recruited 146 subjects including 38 diabetes patients with hypertriglyceridemia, 33 diabetes patients without hypertriglyceridemia, 35 hypertriglyceridemia subjects, and 40 healthy subjects as the normal control group. Serum fasting active GLP-1 was tested with ELISA in the four groups, and associations with insulin resistance were analysed. Serum fasting active GLP-1 levels were significantly increased in hypertriglyceridemia subjects with or without T2DM compared with healthy controls, particularly hypertriglyceridemia patients with T2DM (p

Introduction and Aim: The management of diabetes is a great challenge in this era due to several factors. The financial burden of the medications and the complications of diabetes create management demanding especially in the Indian population. A high protein-rich diet is beneficial in controlling hyperglycemia in diabetic patients. Different amino acids play roles in reducing blood glucose levels in diabetes. Certain amino acids trigger hypoglycemia in diabetes by inducing the gut hormone, Glucagon-like peptide -1(GLP-1) secretion. L-tryptophan is one among them and is present in many of the food items like poultry, beans, seeds, nuts, etc., This study using albino rats focuses on the effect of L-tryptophan on intestinal GLP-1 secretion in diabetic rats by evaluating the blood glucose level, intestinal GLP-1, and intestinal histology of diabetic rats after tryptophan administration.Materials and Methods: Single dose of intraperitoneal injection of STZ (50mg/kg) used to develop diabetic model and orogastric gavage of tryptophan (50mg/kg) was done. Intestinal GLP-1 and blood glucose assay and intestinal histology were the parameters studied.Results: The results showed a significant reduction in blood glucose level and an increased secretion of intestinal GLP-1(p=0.001) in diabetic rats by tryptophan administration and recovery was seen in intestinal histology. In conclusion, in our study, the administration of L- tryptophan in diabetic rats induced a hypoglycemic effect by GLP-1 secretion and restored normal histology.Conclusion: Tryptophan administration showed hypoglycemic effect on diabetic rats as the blood glucose level was reverted to normal and the hypoglycemic effect of L-tryptophan in diabetic rats could be due to increased GLP-1 secretion.

This communication provides a contemporary classification of glucagon-like peptide 1 receptor agonists (GLP1RAs) based on indication, route, and frequency of administration, which could support a person-centric approach to treatment choice. It includes all recently developed GLP1RAs as well as those in advanced stages of clinical study. Keeping pace with current trends in pharmacology and metabolic medicine, it attempts to bring clarity and simplicity to a complex spread of information.

Exenatide is a small therapeutic peptide being currently used in clinic for the treatment of diabetes mellitus type II, however, displaying a short blood circulation time which makes two daily injections necessary. Covalent polymer modification of a protein is a well-known approach to overcome this limitation, resulting in steric shielding, an increased size and therefore a longer circulation half-life. In this study, we employed site-selective C-terminal polymer ligation of exenatide via copper-catalyzed azide-alkyne-cycloaddition (CuAAC) to yield 1:1-conjugates of either poly(ethylene glycol) (PEG) or linear polyglycerol (LPG) of different molecular weights. Our goal was to compare the impact of the two polymers on size, structure and activity of exenatide on the in vitro and in vivo level. Both polymers did not alter the secondary structure of exenatide and expectedly increased its hydrodynamic size, where the LPG-versions of exenatide showed slightly smaller values than their PEG-analogs of same molecular weight. Upon conjugation, GLP-1 receptor activation was diminished, however, still enabled maximum receptor response at slightly higher concentrations. Exenatide modified with a 40 kDa LPG (Ex-40-LPG) showed significant reduction of the blood glucose level in diabetic mice for up to 72 h, which was comparable to its PEG-analog, but 9-fold longer than native exenatide (8 h).