Intestinal Glucose Research Articles

Inhibitory activity of Urena lobata leaf extract on alpha-amylase and alpha-glucosidase: in vitro and in silico approach.

In food ingestion, alpha-glucosidase (α-glucosidase) and alpha-amylase (α-amylase) are enzymes that are responsible to convert a carbohydrate into glucose. Inhibition of both enzyme activities can prolong absorption of glucose in intestine and reduce post-prandial increase of blood glucose concentration, thus, it is beneficial for type-2 diabetes treatment. Traditionally, Urena lobata (U.lobata) has been used to manage diabetes, but the scientific proof of this claim remains scarce. Therefore, the objective of thisstudy to examine the anti-diabetic potential of U.lobata leaf extract through inhibition of α-amylase and α-glucosidase. U.lobata leaf extract was obtained through extraction process using ethanol and the chemical compounds in the extract were analyzed by liquid chromatography-mass spectra (LC-MS). The inhibitory activity of U.lobata on α-glucosidase and α-amylase was evaluated by in silico using docking server, whereas in vitro enzymatic assays were using para-nitrophenyl-α-d-glucopyranoside (α-NPG) and starch as substrates. The data were presented as mean±SD and the IC50 value was calculated using SPSS. U.lobata leaf extract showed inhibitory activity on α-glucosidase and α-amylase with the IC50 value was 43.73 and 83.73μg/mL, respectively, meanwhile, acarbose as standard has IC50 value at 1.14 and 0.08μg/mL. Molecular docking study indicated β-sitosterol and stigmasterol from U.lobata extract have a huge inhibitory activity both on α-amylase and α-glucosidase based on inhibition constant (Ki) value. Ethanolic extract of U.lobata showed inhibition activity on α-glucosidase stronger than on α-amylase as antidiabetic.

Gut Microbiota Modulation In Diabetic Patients

Metabolic disorders and diabetes mellitus are one of the major complex public health problems in the world, and in fact are becoming a global epidemic. It is associated with an increased risk of a large number of complications, including dyslipidemia, cardiovascular disease. The microbiota modulates inflammation, metabolizes indigestible food components, affects intestinal permeability, glucose and lipid metabolism, insulin sensitivity, and overall energy homeostasis. The study investigated the effect of a multistrain probiotic on the intestinal microflora in diabetic patients. As a result of the work carried out, it was shown that the microbiome of patients with diabetes mellitus differs from normal and is depleted in bifidobacteria and some butyrate producers, such as Subdoligranulum, but enriched in Prevotella. The use of a multi-strain probiotic has led to an increase in the biodiversity of the intestinal microflora. Also, in the fecal samples, the content of acetate and butyrate increased, while the concentration of propionate decreased markedly.

Tolerance assessment of dietary bile acids in common carp (Cyprinus carpio L.) fed a high plant protein diet

This study was conducted to investigate the tolerance dose of bile acids as a feed additive in high plant protein (PP) diets of common carp (Cyprinus carpio L.), by evaluating the responses in growth performance, hepatopancreas and intestinal histology, and glucose and lipid metabolism regulation. Three isonitrogenous and isoenergetic diets (36% PP and 10% fish meal) were prepared with bile acids supplementation of 0 (B0), 60 (B60), and 600 (B600) mg/kg, in which B600 was assayed as 10-fold the maximum recommended level (60 mg/kg) obtained by a previous efficacy test. Each diet was fed to six replicates of 30 common carps (initial body weight = 13.7 ± 0.01 g). Bile acids supplementation decreased feed conversion rate, hepatopancreas-somatic index, and hepatopancreas lipid content significantly. Dietary bile acids improved histopathological symptoms induced by the high PP diet, accompanied with down-regulated inflammatory responses (tnfα, il1β, il10, and tgfβ1) in distal intestine; and up-regulated anti-inflammatory cytokines (il10), but reduced apoptosis response (cleaved caspase3, detected by immunofluorescence staining) in the hepatopancreas. The ameliorated pathological symptoms and liver function in the B60 and B600 groups were closely related to the improved glucose metabolism regulation, with decreased fasting blood glucose and increased gluconeogenesis enzyme activity (G6Pase). Simultaneously, improved lipid metabolism was observed with up-regulated lipolysis (atgl) and bile acids synthesis (cyp7a1 and cyp8b1), but down-regulated cholesterol synthesis (hmgcr) gene-related mRNA, together with enhanced cholesterol transportation and bile acid recirculation to reduce lipid accumulation in the hepatopancreas. The phosphorylation of ERK1/2 was positively regulated by the systematic recovery of metabolic liver disease induced by the high PP diet. In conclusion, addition of 60 mg/kg bile acids is effective in common carp, with a 10-fold safety margin in commercial feed.

Modeling continuous glucose monitoring with fractional differential equations subject to shocks

Continuous Glucose Monitoring (CGM) produces long time-series of noisy observations of a single variable (tissue glucose concentration), whose evolution may be explained by a dynamical model. In order to represent the unknown mixture of possible control mechanisms of different orders affecting the measured variable, a fractional differential approach seems justified. In any case, variations in food intake and/or physical activity ought to be taken into account if a plausible interpretation of the dynamics is to be obtained. In the present work, the mathematical construction and the numerical implementation of a Fractional Differential Equations (FDE) initial value problem are systematically reviewed, with the intent of offering the reader a concise and mathematically rigorous description of this approach. An FDE model for CGM is formulated: the model includes compartments for stomach and intestinal glucose contents and for blood and tissue (subcutaneous) glucose concentrations, as well as the shock effects of food ingestion and of increased glucose consumption due to physical activity. The model parameters, including the (non-integer) order of differentiation, are estimated from CGM observations on six Type 1 diabetic patients. The best-fit fractional orders for the six subjects range from 1.59 to 2.13. For comparison, best fits have also been computed for all subjects using an average fractional order of 1.9 and integer orders of 1 and 2.The results indicate that in the case of CGM the fractional differential model, which should be physiologically more appropriate, in fact fits the data much better than the first-order model and also better than the 2nd-order model.

Impact of flavonol extracts derived from green tea or targeted flavonols as secondary ingredients on intestinal glucose transport.

The online version contains supplementary material available at 10.1007/s13197-021-05140-2.

Synthesis and α-Glucosidase Inhibition Activity of 2-[3-(Benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl]-N-arylacetamides: An In Silico and Biochemical Approach.

Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 μM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 μM). Furthermore, a good agreement was observed between in silico and in vitro modes of study.

Acute Low-Intensity Treadmill Running Upregulates the Expression of Intestinal Glucose Transporters via GLP-2 in Mice.

The effects of exercise on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training increases the expression of molecules involved in carbohydrate digestion and absorption. Exercise was also shown to increase the blood concentration of glucagon-like peptide-2 (GLP-2), which regulates carbohydrate digestion and absorption in the small intestine. Therefore, we investigated the effects of exercise on the expression of molecules involved in intestinal digestion and absorption, including GLP-2. Six-week-old male mice were divided into a sedentary (SED) and low-intensity exercise (LEx) group. LEx mice were required to run on a treadmill (12.5 m/min, 1 h), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest, and plasma, jejunum, ileum, and colon samples were collected, followed by analysis via IHC, EIA, and immunoblotting. The levels of plasma GLP-2 and the jejunum expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter 2 (GLUT2) were higher in LEx mice. Thus, we showed that acute low-intensity exercise affects the expression of molecules involved in intestinal carbohydrate digestion and absorption via GLP-2. Our results suggest that exercise might be beneficial for small intestine function in individuals with intestinal frailty.

The Effects of Thyroid Hormones and Their Abnormalities on Intestinal and Hepatic Glucose Metabolism

The Effects of Thyroid Hormones and Their Abnormalities on Intestinal and Hepatic Glucose Metabolism

Beta-Glucan From Barley Attenuates Post-prandial Glycemic Response by Inhibiting the Activities of Glucose Transporters but Not Intestinal Brush Border Enzymes and Amylolysis of Starch

Beta (β)-glucan (BG) from cereal grains is associated with lowering post-prandial blood glucose but the precise mechanism is not well-elucidated. The main aim of this study was to understand the mechanism through which BG from barley affects post-prandial glycemic response. Waffles containing 0, 1, 2, and 3 g barley BG and the same amount of available carbohydrate (15 g) were fed to the TIM-1 dynamic gastrointestinal digestion system to study the effect of BG on starch hydrolysis. Intestinal acetone powder and Xenopus laevis oocytes were used to study BG's effect on mammalian intestinal α-glucosidase and glucose transporters. The presence of BG did not significantly affect the in vitro starch digestion profiles of waffles suggesting that BG does not affect α-amylase activity. Intestinal α-glucosidase and glucose transport activities were significantly (p < 0.0001) inhibited in the presence of barley BG. Interestingly, BG viscosity did not influence α-amylase, α-glucosidase, GLUT2, and SGLT1 activities. This study provides the first evidence for the mechanism by which BG from barley attenuates post-prandial glycemic response is via alteration of α-glucosidase, GLUT2, and SGLT1 activity, but not amylolysis of starch. The decrease in post-prandial blood glucose in the presence of BG is likely a consequence of the interaction between BG and membrane active proteins (brush border enzymes and glucose transporters) as opposed to the commonly held hypothesis that increased viscosity caused by BG inhibits starch digestion.

Purification, characterization and hypoglycemic activity of glycoproteins obtained from pea (Pisum sativum L.)

This study aimed to isolate and characterize the structures of glycoproteins from peas and determine their hypoglycemic activity. The crude pea glycoproteins (PGP) were extracted by hot water and purified by diethylaminoethyl (DEAE)-Sepharose chromatography and Sephadex G-100 size-exclusion chromatography in sequence. Then three main fractions were obtained, namely PGP1, PGP2 and PGP3, with molecular weights of 897 615, 846 740 and 1 194 692Da, respectively. The physical and chemical properties of the three fractions were evaluated and compared by Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), scanning electron microscope (SEM), high performance liquid chromatography (HPLC) and other analytical techniques. The fraction PGP2 with the highest hypoglycemic activity, was screened using the Caco-2 monolayer cell model. It can inhibit the uptake of glucose in the small intestine, as well as the activities of maltase and sucrase. After simulated gastrointestinal digestion, PGP2 significantly enhanced the inhibitory effect of α-glucosidase, and slightly reduced the inhibitory ability of α-amylase. In summary, PGP2 possessed strong hypoglycemic activity after digestion. These results indicated that PGP2 has the potential to be developed into a functional food or natural medicine for the treatment of type 2 diabetes mellitus.

An In Vitro Study on the Effects of Selected Natural Dietary Fiber from Salad Vegetables for Lowering Intestinal Glucose and Lipid Absorption.

Salad vegetables are good sources of dietary fiber and are becoming increasingly popular among consumers. Therefore, these plants have the potential to be developed as functional foods. Using an in vitro model, this study investigated the physical properties and intestinal glucose and lipid absorption capacities of dry dietary fiber from vegetables typically consumed in salads (types of lettuce, including red oak, red coral, green oak, butterhead, and cos). Fiber was prepared from each type of lettuce using an enzymatic method and then characterized. Physical properties, including solubility and water-binding, swelling, cation-exchange, and oil-binding capacities, and antihyperglycemic and antihypercholesterolemic effects of fiber were investigated. The hydration capacity of total dietary fiber and insoluble fiber from the majority of sources was significantly different from that of cellulose. Adsorption and diffusion of glucose were directly proportional to incubation time, and the diffusion rate was significantly lower in the treatments containing fiber compared to the cellulose control. Fiber from these vegetables also inhibited amylase and alpha-glucosidase activities. Moreover, fiber from all sources exhibited significantly higher sodium cholate and cholesterol-binding capacity compared to cellulose, and also retarded pancreatic cholesterol esterase activity in a concentration-dependent manner. This study demonstrates that natural dietary fiber from salad vegetables can reduce glucose and lipid absorption and breakdown rates, thus preventing increases in postprandial blood glucose and cholesterol levels, which can be beneficial to human health.

Intestinal SGLT1 as a therapeutic target in COVID-19-related diabetes: A "two-edged sword" hypothesis.

Emerging data are linking coronavirus disease 2019 (COVID‐19) with an increased risk of developing new‐onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID‐19‐induced diabetes, with the pancreas, liver, and adipose tissue being under the spotlight of medical research. Sodium‐glucose co‐transporters (SGLT) 1 represent important regulators of glucose absorption, expressed in the small intestine where they mediate almost all sodium‐dependent glucose uptake. Similar to what happens in diabetes and other viral infections, SGLT1 upregulation could result in increased intestinal glucose absorption and subsequently promote the development of hyperglycaemia in COVID‐19. Considering the above, the question whether dual SGLT (1 and 2) inhibition could contribute to improved outcomes in such cases sounds challenging, deserving further evaluation. Future studies need to clarify whether putative benefits of dual SGLT inhibition in COVID‐19 outweigh potential risks, particularly with respect to drug‐induced euglycaemic diabetic ketoacidosis, gastrointestinal side effects, and compromised host response to pathogens.

Metformin Treatment of Pediatric Obesity.

* Abbreviations: FDA — : US Food and Drug Administration RCT — : randomized controlled trial T2DM — : type 2 diabetes mellitus Childhood obesity has steadily become a contemporary epidemic with serious public health implications.1 Approximately 70% of children with obesity will remain obese in adulthood.2 Obesity is a risk factor for development of atherosclerosis and type 2 diabetes mellitus (T2DM),3 and its prevention and management represents a priority for pediatric primary care providers. This underscores the need for evidence-based interventions for children and adolescents with obesity, including pharmacotherapy.4 Metformin is US Food and Drug Administration (FDA) approved for use in children 10 years of age and older with T2DM and has been used off label to achieve weight loss in children. In the current issue of Pediatrics , Masarwa et al5 present a systematic review of the safety and efficacy of metformin use from randomized controlled trials (RCTs) in children and adolescents. The authors demonstrated that metformin therapy resulted in modest benefits in reduction of BMI in those with obesity. Among the 14 RCTs in which BMI was reported, metformin was modestly efficacious at decreasing BMI (range of mean changes: −2.70 to 1.30) compared with a placebo (−1.12 to 1.90). As pointed out by the authors, the results across the studies were heterogeneous, with 11 RCTs suggesting that it decreased BMI, whereas 3 RCTs revealed an increase in BMI. Among the 7 RCTs in which a BMI z score was reported, metformin consistently resulted in a decrease … Address correspondence to Vandana Raman, MD, Division of Endocrinology, Department of Pediatrics, University of Utah School of Medicine, 81 N Mario Capecchi Dr, Salt Lake City, UT 84113. E-mail: vana.raman{at}hsc.utah.edu

Kandungan Fenolik dan Flavonoid Total Daun Macaranga hispida (Blume) Mull. Arg sebagai Kandidat Obat Antidiabetes

Diabetes Mellitus (DM) is one of the non communicable diseases (NCDs) with the largest number of deaths in the world. The Macaranga hispida (Blume) Mull. Arg is a source of phenolic compounds. Phenolic is grouped as polyphenols group that widely functioned as antidiabetic. The α-glucosidase enzyme plays a role in the forming of glycoproteins and glycolipids. The α-glucosidase enzyme can be used for antidiabetic activity assay because of its capability on breaking down carbohydrate into glucose in the human small intestine. This study aimed to determine phenolic content, total flavonoid content, and antidiabetic activity of M. hispida leaves extract and its fraction. The extract and fraction were tested for the phenolic levels using Folin-Ciocalteau method, the total flavonoid using alumunium chloride method, and the antidiabetic activity using α-glukosidase method. The yield of methanolic extract of the Macaranga hispida was 10.23%. Phenolic content of the ethyl acetate fraction from the methanolic extract was 8.411 mg, equivalent to gallic acid/100 mg extract. Total flavonoid content was 6.14 ± 0.31b/b μg/mL. Antidiabetic activity assay of the extract and the fractions of Macaranga hispida resulted the highest antidiabetic activity (IC50) was in the ethyl acetate fraction with IC50 value 21.91 μg / mL.

Effects of Standard vs Energy-Dense Formulae on Gastric Retention, Energy Delivery, and Glycemia in Critically Ill Patients.

Energy-dense formulae are often provided to critically ill patients with enteral feed intolerance with the aim of increasing energy delivery, yet the effect on gastric emptying is unknown. The rate of gastric emptying of a standard compared with an energy-dense formula was quantified in critically ill patients. Mechanically ventilated adults were randomized to receive radiolabeled intragastric infusions of 200 mL standard (1 kcal/mL) or 100 mL energy-dense (2 kcal/mL) enteral formulae on consecutive days in this noninferiority, blinded, crossover trial. The primary outcome was scintigraphic measurement of gastric retention (percentage at 120 minutes). Other measures included area under the curve (AUC) for gastric retention and intestinal energy delivery (calculated from gastric retention of formulae over time), blood glucose (peak and AUC), and intestinal glucose absorption (using 3-O-methyl-D-gluco-pyranose [3-OMG] concentrations). Comparisons were undertaken using paired mixed-effects models. Data presented are mean ± SE. Eighteen patients were studied (male/female, 14:4; age, 55.2 ± 5.3 years). Gastric retention at 120 minutes was greater with the energy-dense formula (standard, 17.0 ± 5.9 vs energy-dense, 32.5 ± 7.1; difference, 12.7% [90% confidence interval, 0.8%-30.1%]). Energy delivery (AUC120 , 13,038 ± 1119 vs 9763 ± 1346 kcal/120 minutes; P = 0.057), glucose control (peak glucose, 10.1 ± 0.3 vs 9.7 ± 0.3 mmol/L, P = 0.362; and glucose AUC120 8.7 ± 0.3 vs 8.5 ± 0.3 mmol/L.120 minutes, P = 0.661), and absorption (3-OMG AUC120 , 38.5 ± 4.0 vs 35.7 ± 4.0 mmol/L.120 minutes; P = .508) were not improved with the energy-dense formula. In critical illness, administration of an energy-dense formula does not reduce gastric retention, increase energy delivery to the small intestine, or improve glucose absorption or glucose control; instead, there is a signal for delayed gastric emptying.

Phospholipase C signal mediated the glucose-induced changes of glucose absorption and lipid accumulation in the intestinal epithelial cells of yellow catfish Pelteobagrus fulvidraco.

In present study, we explored the effects and the underlying mechanisms of phospholipase C (PLC) mediating glucose-induced changes in intestinal glucose transport and lipid metabolism by using U-73122 (a PLC inhibitor). We found that glucose incubation activated the PLC signal and U-73122 pre-incubation alleviated the glucose-induced increase in plcb2, plce1 and plcg1 mRNA expression. Meanwhile, U-73122 pre-treatment blunted the glucose-induced increase in sodium/glucose co-transporters 1/2 mRNA and protein expressions. U-73122 pre-treatment alleviated the glucose-induced increase in TAG content, BODIPY 493/503 fluorescence intensity, lipogenic enzymes (glucose 6-phospate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), malic enzyme and fatty acid synthase (FAS)) activity and the mRNA expressions of lipogenic genes and related transcription factors (6pgd, g6pd, fas, acca, srebp1 and carbohydrate response element-binding protein (chrebp)) in intestinal epithelial cells of yellow catfish. Further research found that U-73122 pre-incubation mitigated the glucose-induced increase in the ChREBP protein expression and the acetylation level of ChREBP in HEK293T cells. Taken together, these data demonstrated that the PLC played a major role in the glucose-induced changes of glucose transport and lipid metabolism and provide a new perspective for revealing the molecular mechanism of glucose-induced changes of intestinal glucose absorption, lipid deposition and metabolism.

Artocarpus lacucha Extract and Oxyresveratrol Inhibit Glucose Transporters in Human Intestinal Caco-2 Cells.

Reduction of intestinal glucose absorption might result from either delayed carbohydrate digestion or blockage of glucose transporters. Previously, oxyresveratrol was shown to inhibit α-glucosidase, but its effect on glucose transporters has not been explored. The present study aimed to assess oxyresveratrol-induced inhibition of the facilitative glucose transporter 2 and the active sodium-dependent glucose transporter 1. An aqueous extract of Artocarpus lacucha, Puag Haad, which is oxyresveratrol-enriched, was also investigated. Glucose transport was measured by uptake into Caco-2 cells through either glucose transporter 2 or sodium-dependent glucose transporter 1 according to the culture conditions. Oxyresveratrol (40 to 800 µM) dose-dependently reduced glucose transport, which appeared to inhibit both glucose transporter 2 and sodium-dependent glucose transporter 1. Puag Haad at similar concentrations also inhibited these transporters but with greater efficacy. Oxyresveratrol and Puag Haad could help reduce postprandial hyperglycemic peaks, which are considered to be most damaging in diabetics.

Inhibition of mitochondrial function by metformin increases glucose uptake, glycolysis and GDF-15 release from intestinal cells

Even though metformin is widely used to treat type2 diabetes, reducing glycaemia and body weight, the mechanisms of action are still elusive. Recent studies have identified the gastrointestinal tract as an important site of action. Here we used intestinal organoids to explore the effects of metformin on intestinal cell physiology. Bulk RNA-sequencing analysis identified changes in hexose metabolism pathways, particularly glycolytic genes. Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates. Metformin caused mitochondrial dysfunction and metformin’s effects on 2D-cultures were phenocopied by treatment with rotenone and antimycin-A, including upregulation of GDF15 expression, previously linked to metformin dependent weight loss. Gene expression changes elicited by metformin were replicated in 3D apical-out organoids and distal small intestines of metformin treated mice. We conclude that metformin affects glucose uptake, glycolysis and GDF-15 secretion, likely downstream of the observed mitochondrial dysfunction. This may explain the effects of metformin on intestinal glucose utilisation and food balance.

Hypothalamic detection of macronutrients via multiple gut-brain pathways

Food intake is tightly regulated by complex and coordinated gut-brain interactions. Nutrients rapidly modulate activity in key populations of hypothalamic neurons that regulate food intake, including hunger-sensitive agouti-related protein (AgRP)-expressing neurons. Because individual macronutrients engage specific receptors in the gut to communicate with the brain, we reasoned that macronutrients may utilize different pathways to reduce activity in AgRP neurons. Here, we revealed that AgRP neuron activity in hungry mice is inhibited by site-specific intestinal detection of different macronutrients. We showed that vagal gut-brain signaling is required for AgRP neuron inhibition by fat. In contrast, spinal gut-brain signaling relays the presence of intestinal glucose. Further, we identified glucose sensors in the intestine and hepatic portal vein that mediate glucose-dependent AgRP neuron inhibition. Therefore, distinct pathways are activated by individual macronutrients to inhibit AgRP neuron activity.

Chemosensing in enteroendocrine cells: mechanisms and therapeutic opportunities.

Enteroendocrine cells (EECs) are scattered chemosensory cells in the intestinal epithelium that release hormones with a wide range of actions on intestinal function, food intake and glucose homeostasis. The mechanisms by which gut hormones are secreted postprandially, or altered by antidiabetic agents and surgical interventions are of considerable interest for future therapeutic development. EECs are electrically excitable and express a repertoire of G-protein coupled receptors that sense nutrient and nonnutrient stimuli, coupled to intracellular Ca2+ and cyclic adenosine monophosphate. Our knowledge of EEC function, previously developed using mouse models, has recently been extended to human cells. Gut hormone release in humans is enhanced by bariatric surgery, as well as by some antidiabetic agents including sodium-coupled glucose transporter inhibitors and metformin. EECs are important potential therapeutic targets. A better understanding of their chemosensory mechanisms will enhance the development of new therapeutic strategies to treat metabolic and gastrointestinal diseases.