Postprandial Blood Glucose Elevation Research Articles

Regular Intermittent Aerobic Exercise Reduces Arterial Stiffness Associated with Postprandial Hyperglycemia in Middle-Aged and Older Individuals

Hardening of arterial walls associated with elevated postprandial blood glucose levels increases the risk of cardiovascular disease; however, the impact of intermittent aerobic training on reducing arterial stiffness is unknown. The aim of this study was to examine the chronic effects of intermittent aerobic exercise on arterial stiffness during hyperglycemia in middle-aged adults: 30 healthy middle-aged adults were randomly assigned to an 8-week intermittent aerobic training group (n = 15, jogging or running, 30 min/run, 3 times/week, 65% reserve heart rate) and a control group (n = 15, no training). Pulse wave velocity (PWV) of carotid-femoral (cf) and brachial-ankle (ba), heart rate, blood pressure, and blood glucose was measured before a 75 g oral glucose tolerance test (OGTT) and 30, 60, and 90 min after the test, before the exercise intervention, and 4 and 8 weeks after intervention. The baPWV and blood glucose levels before the intervention were elevated at 30, 60, and 90 min in both groups compared to levels before the 75 g OGTT (p < 0.01). The baPWV and blood glucose levels after 4 and 8 weeks of intervention were unchanged in the training group compared to that before the 75 g OGTT, but increased at 30, 60, and 90 min in the control group compared to that before the 75 g OGTT (p < 0.01). The baPWV and blood glucose levels at 30 and 60 min after the 75 g OGTT after 4 and 8 weeks of intervention were lower in the training group than in the control group (p < 0.01). These results indicate that intermittent aerobic exercise training may reduce the acute increase in arterial stiffness after hyperglycemia.

Exploring the Blood Glucose-Lowering Potential of the Umami Peptides LADW and EEAEGT Derived from Tuna Skeletal Myosin: Perspectives from α-Glucosidase Inhibition and Starch Interaction.

This study aimed to explore the potential of umami peptides for lowering blood glucose. Molecular docking results showed that the peptides LADW and EEAEGT bound to the active amino acid residues of α-glucosidase via hydrogen bonds and Van der Waals forces, a finding supported by an independent gradient model (IGM). Molecular dynamics (MD) simulations demonstrated that the peptides LADW and EEAEGT can decelerate the outward expansion of α-glucosidase and reduce amino acid fluctuations at the active site. In vitro findings indicated that the peptides LADW and EEAEGT showed potent inhibitory activity against α-glucosidase, with IC50 values of 4.40 ± 0.04 and 6.46 ± 0.22 mM, respectively. Furthermore, MD simulation and morphological observation results also revealed that LADW and EEAEGT alter starch structure and form weak interactions with starch through intermolecular hydrogen bonding, leading to the inhibition of starch hydrolysis. Peptides inhibit the ability of starch to produce reducing sugars after simulated gastrointestinal digestion, providing additional evidence of the inhibition of starch hydrolysis by the added peptides. Taken together, these findings suggest that consuming the umami peptides LADW and EEAEGT may alleviate postprandial blood glucose elevations via inhibiting α-glucosidase and starch hydrolysis.

Effect of dietary fiber-enriched brown rice crackers on suppressing elevation of blood glucose level

Background: Rice crackers are composed of carbohydrates refined from rice and enjoyed as a snack in Japan. Most rice crackers are crafted from white rice, and the potential postprandial blood glucose rise following their consumption may pose a clinical concern. Brown rice contains more dietary fiber than white rice and has been reported to suppress elevations of blood glucose. Dietary fiber-enhanced brown rice crackers have a significantly higher dietary fiber content than regular brown rice crackers and can be expected to suppress blood glucose elevations more reliably.Methods: We conducted a crossover trial in humans using white rice crackers and dietary fiber-enhanced brown rice crackers to investigate the effect of dietary fiber-enhanced brown rice crackers on postprandial blood glucose elevations. Participants ingested the 100 g rice crackers with 200 mL water for 10 min, and blood was collected from the fingertip at 7 time points: baseline, and at 15, 30, 45, 60, 90, and 120 min after ingestion of the rice cracker. The primary outcome measure was the blood glucose levels, and the secondary outcome measure was the incremental area under curve of blood glucose.Results: Glucose levels and incremental areas under curve at 60 min and 120 min after intake were significantly lower with dietary fiber-enhanced brown rice crackers than with white rice crackers. Incremental area under curves at 60 min and 120 min after intake of rice crackers were also significantly lower in dietary fiber-enhanced brown rice crackers than white rice crackers.Conclusions: Ingesting dietary fiber-enhanced brown rice crackers instead of white rice crackers could be useful for achieving better glycemic control.Keywords: Brown rice crackers, Dietary fiber, Postprandial blood glucose

Pharmaceutical Food Science: Search for Bio-Functional Molecules Obtained from Natural Resources to Prevent and Ameliorate Lifestyle Diseases.

In this review, our resent pharmaceutical food science research for bio-functional molecules obtained from natural resources that contribute to i) suppression of postprandial blood glucose elevation and/or improvement of glucose tolerance and ii) reduction of visceral fat accumulation and improvement of lipid metabolism were summarized. Based on studies using MONOTORI science, salacinol (1), neokotalanol (4), and trans-tiliroside (20) have been approved or notified by the Consumer Affairs Agency in Japan as functional substances in food with health claims, Food for Specified Health Use and Food with Functional Claims.

Differences and similarities of albumins from japonica rice bran, japonica, indica, and javanica rice endosperm in the suppressive effect of postprandial blood glucose elevation

AbstractSuppression of rapid increase in blood glucose level using food components can prevent diabetes. To use functional food components from natural resources, information regarding the plant varieties and plant parts where the component exists is important for the effective extraction and the effective use of biological resources. We have previously found that proteins from the albumin fraction of rice endosperm are indigestible and adsorb glucose to suppress postprandial blood glucose elevation in vivo. However, the variety and location of this functional protein remain unknown. We investigated whether water‐soluble fraction from the endosperm of indica and javanica rice and red and middle bran of japonica rice contains functional albumin observed in the endosperm of japonica. Middle bran was found to possess an indigestible albumin with the same molecular weight as that in the endosperm of japonica and adsorb a large amount of glucose. Middle‐bran albumin suppressed postprandial blood glucose elevation after oral glucose loading in animal experiments, as well as the rice‐endosperm albumin. As middle bran is the outer layer of the endosperm, many functional components are distributed. Our study can aid the effective use of middle bran, which is predominantly discarded in the process of making rice wine, as a functional food material for the prevention of diabetes mellitus.

A “PAKU-PAKU KOUBO-KUN” containing yeast and mulberry extract postprandial glycemic control in healthy Japanese men and women: a randomized, placebo-controlled, crossover study

Objective: This study’s purpose was to verify the PAKU-PAKU KOUBO-KUN (PPKK) containing yeast and mulberry extract concentrate’s effects on suppressing elevated postprandial blood glucose (PBG).Methods: Two randomized, placebo-controlled, crossover studies (TRIAL-1 and TRIAL-2) were conducted. Both studies included healthy Japanese adults with a maximum PBG concentration (Cmax) in the range of 140–199 mg/dL. Study subjects were randomly assigned to take PPKK or placebo food. Then subjects consumed 200 g of cooked rice within 10 minutes of test food consumption. Blood glucose (BG) levels were evaluated before intervention, and 30 min, 60 min, 90 min, and 120 min after consumption. The main endpoint was the incremental area under the curve (IAUC) of PBG.Results: The analysis included 36 subjects in TRIAL-1 and 41 subjects in TRIAL-2. A combined analysis (n = 71) was conducted. Both individual studies and combined analysis showed that PPKK significantly reduced the IAUC of PBG. In particular, BG levels were significantly lower at 30 min, 60 min, and 90 min after intervention. No adverse effects were identified. Conclusions:These results indicated that PPKK moderated the increase in PBG and enhanced glucose metabolism.Trial registration: UMIN-CTR: UMIN000042445 and UMIN000045341Foundation: Mainichiegao Co., Ltd.Keywords: postprandial blood glucose, yeast, mulberry, prediabetes, glycemic control

Current and emerging medications for the management of obesity in adults.

Current and emerging medications for the management of obesity in adults.

Processing Alaska Pollock Protein (Theragra chalcogramma) into Kamaboko Protein Mitigates Elevated Serum Cholesterol and Postprandial Glucose Levels in Obese Zucker fa/fa Rats

Fish paste products such as kamaboko (KB) are traditional Japanese foods prepared from fish meat. The health-promoting properties of fish proteins and their lysates include improving glucose and lipid metabolism. Although the KB manufacturing process and quality have been examined, limited studies have reported the health-promoting function of KB. This study aimed to evaluate the effects of processing Alaska pollock protein (APP) into KB protein (KBP) on serum lipids levels and postprandial glucose tolerance. Obese male Zucker fa/fa rats were fed on different diets for 4 weeks as follows: APP group, fed on a diet in which APP constituted 25% of total protein intake; KBP group, fed on a diet with APP-processed protein as the protein source; control group, fed on a diet with 100% casein as the protein source. Compared with those in the control group, the serum total cholesterol (TC) level was reduced and the elevated postprandial blood glucose level was mitigated during the high-carbohydrate meal tolerance test in the APP and KBP groups. Further, KBP exerted significantly higher effects on serum TC levels and glucose tolerance than APP.

Physicochemical and functional properties of buckwheat (Fagpopyrum esculentum Moench) albumin

Buckwheat albumin is a promising functional food material that can suppress postprandial blood glucose elevation. Here, we studied the physicochemical and functional properties of buckwheat albumin such as thermal resistance, solubility, and emulsifying and foaming properties to evaluate its potential for application in various foods such as mayonnaise, ice cream, meringues and sponge cake. The denaturation temperature of buckwheat albumin was measured using Differential Scanning Calorimetry (DSC) with and without the addition of dithiothreitol (DTT), and solubility in the pH range of 3.0–6.0 was measured as protein concentration in supernatant before and after heating. Emulsifying and foaming properties of buckwheat albumin were also evaluated before and after hydrolysis by protease. Buckwheat albumin exhibited high thermal resistance with a denaturation temperature of 148.4 °C. However, the peak temperature of DSC thermogram decreased and denaturation enthalpy increased with DTT addition. High solubility was observed at pH 3.0–6.0, which was retained even after heating at 80 °C for 20 min. Furthermore, buckwheat albumin showed high emulsifying and foaming properties in the pH range 3.0–6.0. Although its emulsifying property was decreased on protease treatment, high foaming capacity was maintained even after hydrolysis. These findings suggested that buckwheat albumin can be widely used in various functional foods.

Suppression of postprandial blood glucose elevation by buckwheat (Fagpopyrum esculentum) albumin hydrolysate and identification of the peptide responsible to the function

The objective of this study is to evaluate the suppressive effect of buckwheat-albumin hydrolysate on postprandial hyperglycemia and identify the peptide responsible to the function. Buckwheat-albumin hydrolysate was prepared by using digestive enzymes and was orally administered to rats together with soluble starch. The blood was taken from the tail vein up to 90 min after oral administration to measure blood-glucose and plasma-insulin levels. The peptide with α-amylase inhibitory activity was purified from the buckwheat-hydrolysate by gel-filtration chromatography, α-amylase affinity chromatography, and high performance liquid chromatography (HPLC). The amino-acid sequence of the peptide was identified by a protein sequencer and was compared with that in the buckwheat-genome database. Buckwheat-albumin hydrolysate significantly suppressed the elevation of blood glucose level 15 min after starch administration. The amino-acid sequence of the peptide with α-amylase inhibitory activity was YVEPDCGNLGCCYHC in the parental protein of molecular mass 17.8 kDa and theoretical pI 4.77. The amino-acid sequence, molecular weight, and pI of the parental protein in buckwheat albumin were different from those of α-amylase inhibitor in wheat albumin. This study suggests that the novel α-amylase inhibitor identified in buckwheat albumin is a potential candidate for a functional food material to suppress postprandial blood glucose elevation.

Safety evaluation of a beverage containing mulberry leaf extract.

Mulberry leaf extract (MLE) has known as inhibits elevated postprandial blood glucose level in human. Then, we conducted a randomized, double-blind placebo-controlled parallel-group trial to evaluate safety when a green tea containing MLE is consumed 3 times a day, every day for 4 weeks. The participants (n = 48) were randomly allocated into 2 groups, an MLE beverage group and a control beverage group. The subjects were instructed to drink either a 500 mL green tea containing 550 mg MLE or a 500 mL green tea not containing MLE, 3 times a day, every day, for 4 weeks. No adverse reactions were observed over the 4 weeks trial, and no difference in the incidence of adverse events between the groups. These findings demonstrate that the consumption of a green tea containing 550 mg MLE 3 times a day for 4 weeks is safe for healthy adults.

Inhibitory Effect of Tangeretin and Cardamonin on Human Intestinal SGLT1 Activity In Vitro and Blood Glucose Levels in Mice In Vivo.

Rapid postprandial blood glucose elevation can cause lifestyle-related diseases, such as type II diabetes. The absorption of food-derived glucose is primarily mediated by sodium/glucose cotransporter 1 (SGLT1). Moderate SGLT1 inhibition can help attenuate postprandial blood glucose elevation and prevent lifestyle-related diseases. In this study, we established a CHO cell line stably expressing human SGLT1 and examined the effects of phytochemicals on SGLT1 activity. Among the 50 phytochemicals assessed, tangeretin and cardamonin inhibited SGLT1 activity. Tangeretin and cardamonin did not affect the uptake of L-leucine, L-glutamate, and glycyl-sarcosine. Tangeretin, but not cardamonin, inhibited fructose uptake, suggesting that the inhibitory effect of tangeretin was specific to the monosaccharide transporter, whereas that of cardamonin was specific to SGLT1. Kinetic analysis suggested that the suppression of SGLT1 activity by tangeretin was associated with a reduction in Vmax and an increase in Km, whereas suppression by cardamonin was associated with a reduction in Vmax and no change in Km. Oral glucose tolerance tests in mice showed that tangeretin and cardamonin significantly suppressed the rapid increase in blood glucose levels. In conclusion, tangeretin and cardamonin were shown to inhibit SGLT1 activity in vitro and lower blood glucose level in vivo.

The effect of perennial sow-thistle (Sonchus arvensis) leaf extract on blood glucose and plasma insulin levels of diabetic mice

Abstract. Haryta FS, Listyawati S, Pangastuti A. 2021. The effect of perennial sow-thistle (Sonchus arvensis) leaf extract on blood glucose and plasma insulin levels of diabetic mice. Cell Biol Dev 5: 63-69. The prevalence of diabetes mellitus (DM) has recently increased, thus encouraging drug exploration, especially from natural compounds. One of the potential medicinal plants to reduce blood glucose levels in people with diabetes mellitus is perennial sow-thistle (Sonchus arvensis). This study was conducted to determine the effect of perennial S. arvensis leaf extract on mice's blood glucose levels and plasma insulin levels induced by streptozotocin. This study used six treatment groups, namely: normal, positive control (acarbose 0.13 mg/20ggBW), negative control (aquadest), and treatment group of perennial S. arvensis leaf extract at doses of 50 mg/kgBW, 100 mg/kgBW, and 150 mg/kgBW. The treatments were done by oral administration daily for 14 days. Measurements of blood glucose levels and postprandial plasma insulin levels were measured at 0, 60, and 120 minutes. The test animals were monitored for 14 days, and fasting blood glucose levels were measured on the 7th and 14th days. Data analysis using one-way ANOVA, and if there is a significant difference, it is continued with Duncan's Range Test (DMRT). The results showed that perennial S. arvensis leaf extract could reduce postprandial blood glucose elevation and blood glucose levels in diabetic mice, which were monitored for 14 days. The most effective dose is 150 mg/kgBW. Perennial S. arvensis leaf extract increased postprandial plasma insulin levels at 60 minutes; the most effective dose is 50 mg/kgBW.

Alpha-amylase as molecular target for treatment of diabetes mellitus: A comprehensive review.

The alpha (α)-amylase is a calcium metalloenzyme that aids digestion by breaking down polysaccharide molecules into smaller ones such as glucose and maltose. In addition, the enzyme causes postprandial hyperglycaemia and blood glucose levels to rise. α-Amylase is a well-known therapeutic target for the treatment and maintenance of postprandial blood glucose elevations. Various enzymatic inhibitors, such as acarbose, miglitol and voglibose, have been found to be effective in targeting this enzyme, prompting researchers to express an interest in developing potent alpha-amylase inhibitor molecules. The review mainly focused on designing different derivatives of drug molecules such as benzofuran hydrazone, indole hydrazone, spiroindolone, benzotriazoles, 1,3-diaryl-3-(arylamino) propan-1-one, oxadiazole and flavonoids along with their target-receptor interactions, IC50 values and other biological activities.

The Effects of Gold Kiwifruit Intake Timing with or without Pericarp on Postprandial Blood Glucose Level.

The purpose of this study was to examine how gold kiwifruit pericarp (pericarp is defined as the skin of the fruit) consumption and the timing thereof affect the postprandial blood glucose profile. The study was conducted on twelve healthy volunteers (six men and six women). According to our results, the simultaneous intake of gold kiwifruit with bread and the prior intake of gold kiwifruit evidently suppressed the postprandial blood glucose elevation compared with exclusive bread intake. There was no significant difference in postprandial blood glucose changes between the ingestion of gold kiwifruit pericarp and pulp and that of gold kiwifruit pulp only. The highest postprandial blood glucose elevation was suppressed by 27.6% and the area under the blood glucose elevation curve by 29.3%, even with the exclusive ingestion of gold kiwifruit pulp. We predicted that the ingestion of both the pericarp and pulp of gold kiwifruit would reduce the postprandial blood glucose elevation to a greater extent than that of gold kiwifruit pulp only; however, there was no significant difference between the two. These results indicate that gold kiwifruit consumption significantly suppresses the postprandial blood glucose elevation regardless of pericarp presence or absence and the timing of ingestion.

Skin-related enzyme inhibitory activity by hydrolyzable polyphenols in water chestnut (Trapa natans) husk.

Water chestnut is a floating leaf plant native to Asia and Europe. Its fruit has long been used as an edible and herbal medicine. Water chestnut contains many polyphenols and its consumption can prevent lifestyle-related diseases because it has a suppressive effect on postprandial blood glucose elevation; however, its suitability as a cosmetic material is unknown. Therefore, this study aimed at investigating the antiaging effect of polyphenols contained in the husk of the devil water chestnut (Trapa natans). Six hydrolyzable polyphenols-1,6-di-O-galloyl-β-d-glucopyranose, 1,2,6-tri-O-galloyl-β-d-glucopyranose, 1,6-di-O-galloyl-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucopyranose (nobotanin D), eugeniin, 1,2,3,6-tetra-O-galloyl-β-d-glucopyranose, and trapain-were collected and isolated from the water chestnut husk. These polyphenols showed high antioxidant and antiglycation activities. In addition, inhibitory activities against hyaluronidase, elastase, and collagenase were observed. Especially, eugeniin and trapain, which have many gallic acids and a hexahydroxy-biphenyl group, showed high inhibitory activities. Thus, the polyphenols in water chestnut are beneficial for antiaging effects.

Effect of Lactobacillus rhamnosus GG fermented milk on elevated postprandial blood glucose levels in mice and humans

Effect of <i>Lactobacillus rhamnosus</i> GG fermented milk on elevated postprandial blood glucose levels in mice and humans

Lemongrass (Cymbopogon citratus) Ethanolic Extract Exhibited Activities That Inhibit -glucosidase Enzymes and Postprandial Blood Glucose Elevation

Lemongrass is a common ingredient in Indonesian traditional herbal medicine that potently inhibits carbohydrate hydrolysis. In this study, the in vitro α-glucosidase inhibitory (AGI) activity of lemongrass was compared with its in vivo activity to retard postprandial blood glucose elevation, and the bioactive compounds responsible for these activities were observed. Both water and ethanolic extracts of lemongrass (WLG and ELG, respectively) were tested in vitro for its inhibition of the sucrose and maltose hydrolyzing activities of rat intestinal glucosidase. ELG was observed to exert higher inhibitory activities (Sucrase IC50 = 8.74 mg/mL; Maltase IC50 = 18.93 mg/mL) than WLG. ELG was evaluated for its in vivo activity to retard blood glucose elevation in mice after sucrose, maltose, and glucose consumption. ELG was also fractionated using activity-guided chromatography, followed by liquid chromatography–mass spectrometry and high-performance liquid chromatography (HPLC). In vivo sugar tolerance test confirmed the AGI activity in a non-dose-dependent manner and showed potential additional mechanisms that may prevent postprandial hyperglycemia. The active principles were acquired in methanol-soluble fraction and purified using preparative thin-layer chromatography. HPLC analysis with commercial standards identified caffeic acid and kaempferol as the compounds responsible for the bioactivity of ELG. Results showed that lemongrass has the potential as herbal medicine ingredient in the management of diabetes.

The Antidiabetic Agent Acarbose Improves Anti-PD-1 and Rapamycin Efficacy in Preclinical Renal Cancer.

Simple SummaryAlthough immune-stimulatory and targeted therapies benefit many patients with metastatic kidney cancer, a sizeable proportion of patients fail to respond. Recent studies in mice demonstrate that nutrient-limiting dietary interventions can improve responses to chemotherapy. However, these studies did not investigate effects on metastasis, and the impact of these interventions on the response to immunotherapy or targeted therapies in kidney cancer is unknown. We therefore studied the effects of a glucose-limiting drug called acarbose, which is used to treat type 2 diabetes, in a spontaneously-metastasizing mouse model of kidney cancer. We found that acarbose slowed kidney cancer growth and promoted protective immune responses. In combination with either an immunotherapy or a targeted therapy used clinically to treat kidney cancer, acarbose led to improved treatment outcomes and reduced lung metastases. Our findings contribute to the emerging idea of using nutrition-based interventions to enhance responses to cancer treatments. Although immune checkpoint inhibitors and targeted therapeutics have changed the landscape of treatment for renal cell carcinoma (RCC), most patients do not experience significant clinical benefits. Emerging preclinical studies report that nutrition-based interventions and glucose-regulating agents can improve therapeutic efficacy. However, the impact of such agents on therapeutic efficacy in metastatic kidney cancer remains unclear. Here, we examined acarbose, an alpha-glucosidase inhibitor and antidiabetic agent, in a preclinical model of metastatic kidney cancer. We found that acarbose blunted postprandial blood glucose elevations in lean, nondiabetic mice and impeded the growth of orthotopic renal tumors, an outcome that was reversed by exogenous glucose administration. Delayed renal tumor outgrowth in mice on acarbose occurred in a CD8 T cell-dependent manner. Tumors from these mice exhibited increased frequencies of CD8 T cells that retained production of IFNγ, TNFα, perforin, and granzyme B. Combining acarbose with either anti-PD-1 or the mammalian target of rapamycin inhibitor, rapamycin, significantly reduced lung metastases relative to control mice on the same therapies. Our findings in mice suggest that combining acarbose with current RCC therapeutics may improve outcomes, warranting further study to determine whether acarbose can achieve similar responses in advanced RCC patients in a safe and likely cost-effective manner.

2078-P: APPL2 Deficiency Diminishes Glucose-Stimulated Insulin Secretion in Pancreatic Beta Cells

In response to elevated postprandial blood glucose, remodeling of F-actin enables exocytosis of insulin granules from pancreatic β cells. Dysregulation of F-actin remodeling contributes to defective glucose-stimulated insulin secretion (GSIS) in β cells and subsequent type 2 diabetes. The adaptor protein APPL1 potentiates GSIS and prevents β cell loss in diabetes, but the role of its close homolog APPL2 in β cell function remains unknown. Here we demonstrated that APPL2 controls GSIS by Rac1-mediated F-actin depolymerization via interaction with Rac GTPase activating protein 1 (RacGAP1). β-cell specific deletion of APPL2 induced defective GSIS and glucose intolerance in mice. Ex vivo study revealed a dramatic reduction in both first- and second-phase GSIS in islets, accompanied by a dysregulation of F-actin remodeling. Consistently, knockdown of APPL2 caused impaired glucose-induced F-actin remodeling and insulin secretion in INS-1E β cells. The defects were mainly due to the inactivation of Rac1- the key player controlling insulin granule secretion via F-actin remodeling. Ectopic expression of constitutively active Rac1 mutant rescued the defective GSIS and F-actin remodeling in APPL2 deficient β cells. Furthermore, we identified RacGAP1 as an interacting partner of APPL2. RacGAP1 interacted with and regulate activity of Rac1, and overexpression of RacGAP1 significantly suppressed glucose-induced F-actin depolymerization, whereas co-expression with APPL2 antagonized this suppressive effect. In addition, the defects in APPL2 knockdown β cells were largely reversed by simultaneous downregulation of RacGAP1 or co-expression of constitutively active Rac1 mutant. In summary, our study suggest that APPL2 potentiates GSIS by antagonizing the inhibitory effect of RacGAP1 on Rac1 activation and F-actin remodeling and insulin secretion in β cells, highlighting the importance of APPL2 in the regulation of GSIS in pancreatic β cells and glucose homeostasis. Disclosure H. Lin: None. Funding National Natural Science Foundation of China (81970675)