Inhibition Of Glucose Absorption Research Articles

The impact of sulphated polysaccharides from Ecklonia maxima on carbohydrate hydrolyzing enzymes, muscle glucose uptake and intestinal glucose absorption ex vivo

Ecklonia maxima is a rich source of bioactive compounds and has been shown to exhibit several biological activities. However, the antidiabetic potential of sulphated polysaccharide (SP) from E. maxima is yet to be fully explored. This study characterised crude and purified SPs from E. maxima using Fourier-transform infrared Spectroscopy, Ultra Performance liquid chromatography-diode array detector (UPLC-DAD) and Nuclear magnetic resonance spectroscopy. The antidiabetic potential of the SPs was assessed via their effect on carbohydrate hydrolysing enzymes (α-amylase and α-glucosidase), glucose uptake in psoas muscles and intestinal glucose absorption ex vivo. The SPs revealed the presence of glucose, galactose, xylose and galacturonic acid. The crude and purified SPs exhibited strong inhibitory effects on α-amylase and α-glucosidase activity. The SPs significantly increased glucose uptake into yeast cells and psoas muscles. The crude and purified SPs significantly reduced intestinal glucose absorption compared to metformin. The SPs displayed notable potential for glucose uptake in yeast cells and psoas muscle and inhibition of glucose absorption in small intestine. The antidiabetic mechanisms of the SPs could be linked to inhibition of α-amylase and α-glucosidase, reduction of intestinal glucose absorption and increase in glucose uptake into the muscles. SPs from E. maxima exhibit strong antidiabetic potentials and can be explored for the management of type-2 diabetes.

Exploring the potential use of Caenorhabditis elegans as an animal model for evaluating chemical-induced intestinal dysfunction

Evaluating intestinal toxicity is crucial for identifying and preventing the harmful effects of environmental chemicals. Owing to the limitations of existing models in evaluating intestinal toxicity, the development of alternative models is urgently needed. This study explored the potential use of the nematode Caenorhabditis elegans as a model animal for assessing chemical-induced intestinal dysfunction. Changes in intestinal permeability and nutrient absorption in C. elegans individuals exposed to four intestine-disrupting chemicals (sodium dodecyl sulfate (SDS), dextran sulfate sodium (DSS), lipopolysaccharide (LPS) and ethanol) were examined using dye stain assays, an enzymatic photometric assay, and fluorescent probe uptake assays. Additionally, epigallocatechin-3-gallate (EGCG), an intestine-protecting phytochemical, was chosen to prevent ethanol-induced intestinal damage. The results indicated that SDS, DSS, LPS, and ethanol compromised the intestinal barrier in C. elegans. SDS had no effect on glucose absorption, but LPS, DSS, and ethanol inhibited or tended to inhibit glucose absorption. SDS, DSS, LPS, and ethanol reduced fatty acid absorption. LPS increased peptide absorption at a low dose but decreased it at a high dose; SDS, DSS, and ethanol attenuated peptide absorption. EGCG protected against the disruption of the intestinal barrier that was induced by ethanol treatment. These results suggest that C. elegans is a suitable surrogate model animal for evaluating chemical-induced intestinal dysfunction. These findings also provide new insights into the effects of SDS, DSS, LPS, and ethanol on intestinal function and highlight the potential of EGCG as a natural dietary intervention to protect individuals who use excess alcohol from intestinal injury.

Antidiabetic Potential of Nypa fruticans Fronds: Inhibition of α-Amylase, α-Glucosidase, and Glucose Absorption In Vivo

Background: Diabetes mellitus (DM) results from insulin resistance or impaired insulin secretion, leading to hyperglycemia, which, in advanced stages, causes macrovascular and microvascular complications. Effective management of postprandial hyperglycemia is critical to reducing these complications. Inhibition of carbohydrate hydrolyzing enzymes such as α-amylase and α-glucosidase offers a therapeutic approach for controlling postprandial glucose levels. While acarbose is a known inhibitor of these enzymes, its long-term use can cause gastrointestinal side effects. Therefore, alternative treatments, such as medicinal plants, are being explored. This study focuses on the antidiabetic potential of the Nipah frond (Nypa fruticans Wurmb), a traditional remedy, which is believed to inhibit glucose absorption and carbohydrate degradation. Methods; Nipah frond powder was extracted using ethanol through maceration. Phytochemical screening was conducted to detect bioactive compounds, and in vivo and in vitro assays were performed to evaluate antidiabetic properties. The inverted intestinal pouch technique assessed glucose absorption, while the Oral Glucose Tolerance Test (OGTT) was conducted on male Wistar rats. Enzyme inhibition assays for α-amylase and α-glucosidase were carried out to measure the extract's effectiveness in inhibiting carbohydrate degradation. Results: In vitro tests demonstrated that the ethanol extract exhibited inhibitory activity against both α-amylase and α-glucosidase enzymes, with IC50 values of 38.493 ± 0.900 ppm and 40.401 ± 0.558 ppm, respectively. In vivo studies using the everted sac technique showed that the extract reduced glucose absorption by 74.10% compared to the control group, similar to acarbose. In the OGTT, administration of 1000 mg/kg BW of Nipah frond extract significantly reduced postprandial glucose levels, with an area under the curve (AUC) comparable to glibenclamide. Conclusion: The ethanol extract of Nypa fruticans fronds demonstrated significant antidiabetic activity by inhibiting α-amylase and α-glucosidase, reducing glucose absorption, and suppressing postprandial hyperglycemia in vivo.

Bitter Phytochemicals Acutely Lower Blood Glucose Levels by Inhibition of Glucose Absorption in the Gut

Bitter Phytochemicals Acutely Lower Blood Glucose Levels by Inhibition of Glucose Absorption in the Gut

Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors: Antidiabetics Medications for Treating Diabetes

Type 2 diabetes (T2D) is a progressive disease, and most patients need to treat with monotherapy and combinations of oral hypoglycaemic drugs. At present about 500 million people worldwide are suffering from T2D. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a novel antidiabetic drug class that mediates epithelial glucose transport at the renal proximal tubules, inhibiting glucose absorption that result in glycosuria, modest weight loss and improve glycaemic control with a low risk of hypoglycaemia. These are used by T2D patients together with diet and exercise, either alone or in combination with other diabetes medicines. The main side-effects of SGLT-2 inhibitors are urinary tract and genital infections, as well as euglycemic diabetic ketoacidosis. Some other probable adverse effects are lower limb amputations, risk of bone fractures, Fournier gangrene, male bladder cancer, female breast cancer, orthostatic hypotension, and acute kidney injury. This mini review explains aspects of SGLT-2 inhibitors with treatment procedures and side-effects.

Solid-state fermentation of green lentils by Lactiplantibacillus plantarum leads to formation of distinct peptides that are absorbable and enhances DPP-IV inhibitory activity in an intestinal Caco-2 cell model.

Food-derived bioactive compounds mimicking the effects of incretin therapies offer promising opportunities for combination therapies with functional foods, where food matrix interactions, gastrointestinal enzyme activity, and in situ bioactivity should be key considerations. In this study, green lentils were solid-state fermented with Lactiplantibacillus plantarum ATCC8014, in vitro digested and exposed to brush border enzymes of a Caco-2 cell monolayer. Intestinal absorption of peptides and DPP-IV inhibitory activity were then investigated. LC-MS/MS profiles showed that peptides mainly originated from parental proteins of the vicilin, convicilin and legumin families. Fermentation led to the formation of more hydrophobic peptides when compared to the unfermented flour and up to 33.6% of them were transported to the basolateral side of a Caco-2 cell monolayer. Peptides with more than 22 amino acids and with a mass greater than 2000 Da were minimally transported. 73 peptides were uniquely identified in the basolateral fraction suggesting that they resulted from the activity of the brush border enzymes. The DPP-IV activity of Caco-2 cells grown as a polarized monolayer was decreased by 37.3% when exposed to in vitro digested 72 h-fermented lentil flour and 10% when exposed to the unfermented one. Inhibition of DPP-IV in the basolateral fluids was improved in a dose-dependent manner and reached 7.9% when 500 mg mL-1 of in vitro digested 72 h fermented lentil flour was used. Glucose absorption and uptake were minimally affected, suggesting that the previously observed hypoglycemic properties of lentils are likely due to activity on DPP-IV rather than on the inhibition of glucose absorption.

Insulin secretory actions of polyphenols of Momordica charantia regulate glucose homeostasis in alloxan-induced type 2 diabetic rats

Abstract Objective Momordica charantia, commonly known as bitter gourd, is traditionally used as remedies for various diseases including diabetes. The main objective of this study is to investigate the in vitro and in vivo insulinotropic and antidiabetic effects of an 80% ethanolic extract of M. charantia (EEMC) fruit, as well as the underlying molecular mechanism involved and preliminary phytochemical screening. Methods The insulin secretion was measured using clonal pancreatic BRIN-BD11 β-cells and isolated mouse islets. The ability of EEMC to inhibit carbohydrate digestive enzymes and glucose absorption and to scavenge free radicals was assessed via starch digestion, glucose diffusion, and 2,2-diphenyl-1-picrylhydrazyl assay methods. The effects of EEMC on a variety of metabolic parameters were evaluated in alloxan-induced type 2 diabetic rats, including lipid profile. Finally, a preliminary phytochemical screening was conducted to identify the active phytoconstituents. Key findings EEMC increased insulin release through the KATP-dependent/cyclic adenosine monophosphate pathway, which depolarizes the β-cell membrane and elevates intracellular calcium. It also inhibited glucose absorption and free radicals, suggesting its potential to delay gastric emptying, attenuate oxidative stress, and reduce inflammatory cytokines. In vivo studies showed that EEMC improves oral glucose tolerance, food intake, fasting blood glucose, plasma insulin, and lipids and promotes intestinal motility. The active phytoconstituents in EEMC, such as flavonoids, alkaloids, tannins, saponins, steroids, and glycosides, are likely responsible for these effects. Conclusion The antihyperglycemic properties of EEMC indicate that it might be a promising candidate for diabetes management. However, additional study into the application of M. charantia in type 2 diabetes is essential.

Elucidation of anti-hyperglycemic activity of Psidium guajava L. leaves extract on streptozotocin induced neonatal diabetic Long-Evans rats

BackgroundPsidium guajava L (Guava) belongs to the Myrtaceae family and has been claimed to possess several pharmacological properties including antidiabetic. ObjectiveThis study was designed to evaluate the anti-hyperglycemic activity of P guajava L leaves aqueous extract on neonatal streptozotocin-induced type 2 diabetic model rats. MethodsStreptozotocin was induced (90 mg/kg) intraperitoneally to 48 h old Long Evans rat pups. After three months, 18 male type-2 diabetic model rats were confirmed by OGTT (FG > 7 mmol/L). Therefore, experimental rats were divided into three groups 2) Diabetic water control (10 ml/kg), 3) Gliclazide treated (20 mg/kg), and 4) Extract treated group (1.25g/kg)] Six normal female rats comprised group 1 [Non-diabetic water control (10 ml/kg)]. All rats were treated orally with their respective treatment for 28 consecutive days. Blood samples were collected on 0 days (by tail cut method) and the end day (by cardiac puncture) of the experiment. The anti-hyperglycemic activity was evaluated by measuring fasting glucose, serum insulin, lipid profile, hepatic glycogen content, and intestinal glucose absorption by standard methods. ResultsThe serum glucose level of extract treated group was decreased by 16% as well as significantly (p<0.05) increased the serum insulin level (M±SD, 0 day vs 28thday; 0.319 ± 0.110 vs 0.600 ± 0.348, μg/L). Moreover, the extract-treated group also significantly (p<0.05) enhanced liver glycogen content and inhibited glucose absorption from the upper intestine. Besides, a significant (p < 0.05) reduction of LDL-cholesterol level was found in the extract-treated group (M±SD, 55 ± 33 vs 14 ± 9, mg/dl) compared with baseline values where other groups did not show any statistically remarkable changes. ConclusionCurrent study concludes that P guajava leaves aqueous extract enhances insulin secretion from pancreatic beta-cells and promotes glycogen synthesis in the liver. The extract also inhibits glucose absorption from the upper intestine and improves dyslipidemia to some extent. Therefore, possesses the potential for drug development against T2DM.

In Silico Screening and Identification of Antidiabetic Inhibitors Sourced from Phytochemicals of Philippine Plants against Four Protein Targets of Diabetes (PTP1B, DPP-4, SGLT-2, and FBPase).

Current oral medications for type 2 diabetes target a single main physiological mechanism. They either activate or inhibit receptors to enhance insulin sensitivity, increase insulin secretion, inhibit glucose absorption, or inhibit glucose production. In advanced stages, combination therapy may be required because of the limited efficacy of single-target drugs; however, medications are becoming more costly, and there is also the risk of developing the combined side effects of each drug. Thus, identifying a multi-target drug may be the best strategy to improve treatment efficacy. This study sees the potential of 2657 Filipino phytochemicals as a source of natural inhibitors against four targets of diabetes: PTP1B, DPP-4, SGLT-2, and FBPase. Different computer-aided drug discovery techniques, including ADMET profiling, DFT optimization, molecular docking, MD simulations, and MM/PBSA energy calculations, were employed to elucidate the stability and determine the binding affinity of the candidate ligands. Through in silico methods, we have identified seven potential natural inhibitors against PTP1B, DPP-4, and FBPase, and ten against SGLT-2. Eight plants containing at least one natural inhibitor of each protein target were also identified. It is recommended to further investigate the plants' potential to be transformed into a safe and scientifically validated multi-target drug for diabetes therapies.

Food Polyphenols and Type II Diabetes Mellitus: Pharmacology and Mechanisms.

Type II diabetes mellitus and its related complications are growing public health problems. Many natural products present in our diet, including polyphenols, can be used in treating and managing type II diabetes mellitus and different diseases, owing to their numerous biological properties. Anthocyanins, flavonols, stilbenes, curcuminoids, hesperidin, hesperetin, naringenin, and phenolic acids are common polyphenols found in blueberries, chokeberries, sea-buckthorn, mulberries, turmeric, citrus fruits, and cereals. These compounds exhibit antidiabetic effects through different pathways. Accordingly, this review presents an overview of the most recent developments in using food polyphenols for managing and treating type II diabetes mellitus, along with various mechanisms. In addition, the present work summarizes the literature about the anti-diabetic effect of food polyphenols and evaluates their potential as complementary or alternative medicines to treat type II diabetes mellitus. Results obtained from this survey show that anthocyanins, flavonols, stilbenes, curcuminoids, and phenolic acids can manage diabetes mellitus by protecting pancreatic β-cells against glucose toxicity, promoting β-cell proliferation, reducing β-cell apoptosis, and inhibiting α-glucosidases or α-amylase. In addition, these phenolic compounds exhibit antioxidant anti-inflammatory activities, modulate carbohydrate and lipid metabolism, optimize oxidative stress, reduce insulin resistance, and stimulate the pancreas to secrete insulin. They also activate insulin signaling and inhibit digestive enzymes, regulate intestinal microbiota, improve adipose tissue metabolism, inhibit glucose absorption, and inhibit the formation of advanced glycation end products. However, insufficient data are available on the effective mechanisms necessary to manage diabetes.

The antidiabetic effect of methanolic extract of Holarrhena pubescens seeds is mediated through multiple mechanisms of action

Holarrhena pubescens is widely used in Indian and Chinese medicine in the treatment of diabetes. The current work determined the oral hypoglycemic and antidiabetic effects of seed extract in rats. The probable mechanism of action was evaluated in-vitro by α - glucosidase inhibition, glucose metabolism in insulinoma (INS-1) cells to reflect secretion of insulin, and protein glycation inhibition. Its potential for herb-drug interaction was evaluated in the cytochrome P450 3A4 (CYP3A4) inhibition assay. The seed extract increased serum insulin levels and reduced serum blood glucose levels in the oral glucose tolerance test. It also reduced the serum glucose levels in streptozocin-induced diabetes. The extract also inhibited α –glucosidase enzyme activity and demonstrated that it can increase the secretion of insulin from INS to 1-rat insulinoma cell line cells in-vitro in a concentration-dependent manner. However, it had a very weak inhibitory effect on protein glycation and it did not affect the activity of CYP3A4. The results of the study showed that H. pubescens seed extract increases insulin secretion and inhibits glucose absorption both in-vivo and in-vitro with a weak protein glycation inhibitory effect. The herb is devoid of CYP3A4 inhibitory effect indicating that it may not have pharmacokinetic interaction with the drug metabolized by this enzyme.

A novel purgative mechanism of multiflorin A involves changing intestinal glucose absorption and permeability

BackgroundMultiflorin A (MA) is a potential active ingredient of traditional herbal laxative, Pruni semen, with unusual purgative activity and an unclear mechanism, and inhibiting intestinal glucose absorption is a promising mechanism of novel laxatives. However, this mechanism still lacks support and a description of basic research. PurposeThis study aimed to determine the main contribution of MA to the purgative activity of Pruni semen and elucidate the effect intensity, characteristics, site, and mechanism of MA in mice, and determine the novel mechanism of traditional herbal laxatives from the perspective of intestinal glucose absorption. MethodsWe induced diarrhoea in mice by administering Pruni semen and MA, and the defecation behaviour, glucose tolerance, and intestinal metabolism were analysed. The effects of MA and its metabolite on peristalsis of the intestinal smooth muscle were evaluated using an intestinal motility assay in vitro. Intestinal tight junction proteins, aquaporins, and glucose transporters expression were analysed using immunofluorescence; gut microbiota and faecal metabolites were analysed using 16S rRNA and liquid chromatography-mass spectrometry. ResultsMA administration (20 mg/kg) induced watery diarrhoea in over half of the experimental mice. The activity of MA in lowering peak postprandial glucose levels was synchronous with purgative action, with the acetyl group being the active moiety. MA was metabolised primarily in the small intestine, where it decreased sodium-glucose cotransporter-1, occludin, and claudin1 expression, then inhibited glucose absorption, resulting in a hyperosmotic environment. MA also increased the aquaporin3 expression to promote water secretion. Unabsorbed glucose reshapes the gut microbiota and their metabolism in the large intestine and the increasing gas and organic acid promoted defecation. After recovery, the intestinal permeability and glucose absorption function returned, and the abundance of probiotics such as Bifidobacterium increased. ConclusionThe purgative mechanism of MA involves inhibiting glucose absorption, altering permeability and water channels to promote water secretion in the small intestine, and regulating gut microbiota metabolism in the large intestine. This study is the first systematic experimental study on the purgative effect of MA. Our findings provide new insight into the study of novel purgative mechanisms.

Inhibition of Gluconeogenesis by Boldine in the Perfused Liver: Therapeutical Implication for Glycemic Control.

The alkaloid boldine occurs in the Chilean boldo tree (Peumus boldus). It acts as a free radical scavenger and controls glycemia in diabetic rats. Various mechanisms have been proposed for this effect, including inhibited glucose absorption, stimulated insulin secretion, and increased expression of genes involved in glycemic control. Direct effects on glucose synthesis and degradation were not yet measured. To fill this gap, the present study is aimed at ensuring several metabolic pathways linked to glucose metabolism (e.g., gluconeogenesis) in the isolated perfused rat liver. In order to address mechanistic issues, energy transduction in isolated mitochondria and activities of gluconeogenic key enzymes in tissue preparations were also measured. Boldine diminished mitochondrial ROS generation, with no effect on energy transduction in isolated mitochondria. It inhibited, however, at least three enzymes of the gluconeogenic pathway, namely, phosphoenolpyruvate carboxykinase, fructose-bisphosphatase-1, and glucose 6-phosphatase, starting at concentrations below 50 μM. Consistently, in the perfused liver, boldine decreased lactate-, alanine-, and fructose-driven gluconeogenesis with IC50 values of 71.9, 85.2, and 83.6 μM, respectively. Conversely, the compound also increased glycolysis from glycogen-derived glucosyl units. The hepatic ATP content was not affected by boldine. It is proposed that the direct inhibition of hepatic gluconeogenesis by boldine, combined with the increase of glycolysis, could be an important event behind the diminished hyperglycemia observed in boldine-treated diabetic rats.

Annona muricata: Comprehensive Review on the Ethnomedicinal, Phytochemistry, and Pharmacological Aspects Focusing on Antidiabetic Properties

Plants have played an important role over the centuries in providing products that have been used to help combat ailments and diseases. Many products originating from fresh, dried-plant materials, or extracts are utilized as community remedies in traditional practices or even in modern medicine. The Annonaceae family contains different types of bioactive chemical properties, such as alkaloids, acetogenins, flavonoids, terpenes, and essential oil, meaning the plants in this family are potential therapeutic agents. Belonging to the Annonaceae family, Annona muricata Linn. has recently attracted the attention of scientists for its medicinal value. It has been utilized as a medicinal remedy since ancient times to treat and improve various diseases, for example, diabetes mellitus, hypertension, cancer, and bacterial infections. This review, therefore, highlights the important characteristic and therapeutic effect of A. muricata along with future perspectives on its hypoglycemic effect. The most-common name is soursop, referring to its sour and sweet flavors, while in Malaysia, this tree is commonly called 'durian belanda'. Furthermore, A. muricata contains a high content of phenolic compounds in the roots and leaves. In vitro and in vivo studies have shown that A. muricata has the pharmacological effects of anti-cancer, anti-microbial, antioxidant, anti-ulcer, anti-diabetic, anti-hypertensive, and wound healing. With regard to its anti-diabetic effect, mechanisms of inhibiting glucose absorption via α-glucosidase and α-amylase activity inhibition, increasing glucose tolerance and glucose uptake by peripheral tissues, and stimulating insulin release or acting like insulin were deeply discussed. There is still a significant research gap, and future studies are required to conduct detailed investigations and gain a better molecular understanding of A. muricata's anti-diabetic potential, especially by using the metabolomics approach.

Herbal tea, a novel adjuvant therapy for treating type 2 diabetes mellitus: A review

Type 2 diabetes mellitus (T2DM) is a metabolic, endocrine disease characterized by persistent hyperglycemia. Several studies have shown that herbal tea improves glucose metabolism disorders in patients with T2DM. This study summarizes the published randomized controlled trials (RCTs) on herbal tea as a adjuvant therapy for treating T2DM and found that herbal teas have potential add-on effects in lowering blood glucose levels. In addition, we discussed the polyphenol contents in common herbal teas and their possible adverse effects. To better guide the application of herbal teas, we further summarized the hypoglycemic mechanisms of common herbal teas, which mainly involve: 1) improving insulin resistance, 2) protecting islet β-cells, 3) anti-inflammation and anti-oxidation, 4) inhibition of glucose absorption, and 5) suppression of gluconeogenesis. In conclusion, herbal tea, as a novel adjuvant therapy for treating T2DM, has the potential for further in-depth research and product development.

Metabolism toxicity and susceptibility of decabromodiphenyl ether (BDE-209) exposure on BRL cells with insulin resistance.

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance (IR) and has attracted worldwide attention due to its high prevalence. As a typical persistent organic pollutant, decabromodiphenyl ether (BDE-209) has been detected in food and human samples, and the concentration trends increase year by year. In addition, it has been proved to have the potential to increase the risk of IR, but it is rarely reported whether it could aggravate IR in T2DM. Therefore, in this study, the IR-BRL (buffalo rat liver cells with IR) model was applied to study the metabolism toxicity and susceptibility of BDE-209. Results showed that BDE-209 could inhibit glucose absorption and increase the levels of serum total cholesterol (TC) and triglyceride (TG), ultimately leading to the disorder of glucolipid metabolism in IR-BRL cells. Besides, it also could cause cell damage by increasing the levels of aspartate transaminase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) in cells. Moreover, its potential mechanisms were to: (1) affect the transport of glucose, synthesis of glycogen and fatty acid via IRS-1/GLUT4 and IRS-1/PI3K/AKT/GSK-3β pathways; (2) impact the proliferation and differentiation by regulating the expression of Mek1/2, Erk1/2, and mTOR proteins and genes. Furthermore, susceptibility analysis showed that there was a significant synergism interaction between IR and BDE-209, which suggested that IR-BRL cells were more susceptible to the metabolism toxicity induced by BDE-209.

Pharmacology of α-spinasterol, a phytosterol with nutraceutical values: A review.

α-Spinasterol is a phytosterol found in various edible and non-edible plant sources. The edible plant materials containing α-spinasterol include spinach leaves, cucumber fruits, seeds of pumpkin and watermelon, argan seed oil, cactus pear seed oil and Amaranthus sp. It is a bioavailable nutraceutical, and it can cross the blood-brain barrier. It possesses several important pharmacological properties such as anti-diabetes mellitus, antiinflammation, hypolipidemic, antiulcer, neuroprotection, anti-pain and antitumour activities. For this review, literature search was made focusing on the pharmacological properties of α-spinasterol using PubMed and Google Scholar data bases. Recent studies show the promising antidiabetic properties of α-spinasterol. Its anti-diabetic mechanisms include enhancement of insulin secretion, reduction in insulin resistance, anti-diabetic nephropathy, increase in glucose uptake in muscle cells and inhibition of glucose absorption from intestine. Besides, it is a safe antiinflammatory agent, and its antiinflammatory mechanisms include inhibition of cyclooxygenases, antagonism of TRPV1 receptor and attenuation of proinflammatory cytokines and mediators. It is a promising and safe nutraceutical molecule for human health care. Food supplements, value-added products and nutraceutical formulations can be developed with α-spinasterol for the management of diabetes, chronic inflammatory diseases and improving general health. This review provides all scattered pharmacological studies on α-spinasterol in one place and highlights its immense value for human health care.

Opposing roles of the entero-pancreatic hormone urocortin-3 in glucose metabolism in rats

Aim/hypothesisUrocortin-3 (UCN3) is a glucoregulatory peptide produced in the gut and pancreatic islets. The aim of this study was to clarify the acute effects of UCN3 on glucose regulation following an oral glucose challenge and to investigate the mechanisms involved.MethodsWe studied the effect of UCN3 on blood glucose, gastric emptying, glucose absorption and secretion of gut and pancreatic hormones in male rats. To supplement these physiological studies, we mapped the expression of UCN3 and the UCN3-sensitive receptor, type 2 corticotropin-releasing factor receptor (CRHR2), by means of fluorescence in situ hybridisation and by gene expression analysis.ResultsIn rats, s.c. administration of UCN3 strongly inhibited gastric emptying and glucose absorption after oral administration of glucose. Direct inhibition of gastrointestinal motility may be responsible because UCN3’s cognate receptor, CRHR2, was detected in gastric submucosal plexus and in interstitial cells of Cajal. Despite inhibited glucose absorption, post-challenge blood glucose levels matched those of rats given vehicle in the low-dose UCN3 group, because UCN3 concomitantly inhibited insulin secretion. Higher UCN3 doses did not further inhibit gastric emptying, but the insulin inhibition progressed resulting in elevated post-challenge glucose and lipolysis. Incretin hormones and somatostatin (SST) secretion from isolated perfused rat small intestine was unaffected by UCN3 infusion; however, UCN3 infusion stimulated secretion of somatostatin from delta cells in the isolated perfused rat pancreas which, unlike alpha cells and beta cells, expressed Crhr2. Conversely, acute antagonism of CRHR2 signalling increased insulin secretion by reducing SST signalling. Consistent with these observations, acute drug-induced inhibition of CRHR2 signalling improved glucose tolerance in rats to a similar degree as administration of glucagon-like peptide-1. UCN3 also powerfully inhibited glucagon secretion from isolated perfused rat pancreas (perfused with 3.5 mmol/l glucose) in a SST-dependent manner, suggesting that UCN3 may be involved in glucose-induced inhibition of glucagon secretion.Conclusions/interpretationOur combined data indicate that UCN3 is an important glucoregulatory hormone that acts through regulation of gastrointestinal and pancreatic functions.Graphical abstract

SGLT2 Inhibitors in Type 2 Diabetes Mellitus and Heart Failure-A Concise Review.

The incidence of both diabetes mellitus type 2 and heart failure is rapidly growing, and the diseases often coexist. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new antidiabetic drug class that mediates epithelial glucose transport at the renal proximal tubules, inhibiting glucose absorption—resulting in glycosuria—and therefore improving glycemic control. Recent trials have proven that SGLT2i also improve cardiovascular and renal outcomes, including reduced cardiovascular mortality and fewer hospitalizations for heart failure. Reduced preload and afterload, improved vascular function, and changes in tissue sodium and calcium handling may also play a role. The expected paradigm shift in treatment strategies was reflected in the most recent 2021 guidelines published by the European Society of Cardiology, recommending dapagliflozin and empagliflozin as first-line treatment for heart failure patients with reduced ejection fraction. Moreover, the recent results of the EMPEROR-Preserved trial regarding empagliflozin give us hope that there is finally an effective treatment for patients with heart failure with preserved ejection fraction. This review aims to assess the efficacy and safety of these new anti-glycemic oral agents in the management of diabetic and heart failure patients.

Gas Chromatography-Mass Spectrometry Analysis and α-Glucosidase Inhibitory Activity of n-Hexane Extract of Bilajang Bulu (Merremia Vitifolia) Leaves

One of the most effective treatments for diabetes mellitus is to inhibit α-glucosidase, which inhibits glucose absorption by the epithelium membrane of the small intestine. In South Sulawesi, Indonesia, Merremia vitifolia is used as a traditional medicine for the treatment of diabetes. The aims of this study are to (1) assess the extract's ability to inhibit α - glucosidase and (2) identify volatile organic compounds in n-hexane of Merremia vitifolia extract. Extraction was conducted by maceration. The inhibitory activity of quercetin towards α-glucosidase has the IC50 = 2.53 ± 0.16 µg/mL, and by n-Hexane extract of Merremia vitifolia leaves has the IC50 = 14.4 ± 1.52 µg/mL. Then, n-Hexane extract of Merremia vitifolia leaves has strong α-glucosidase inhibitory activity. The compounds that have been identified based on Gas Chromatography-Mass Spectrometry (GC-MS) analysis with similarity index ≥ 89% which are caryophyllene (0.94%), (E)-β-famesene (4.72%), neophytadiene (9.78%), phytol (65.94%), 9,12,15-octadecatrienoic acid (6.71%), 1,5-cyclodecadiene (6.76%), squalene (4.48%), stigmasterol (4.08%), γ-sitosterol (10.20%), Serratol (23.12%), vitamin E (2.78%) and lup-20(29)-en-3-one (21.04%). Based on a literature study, the presence of phytol, neophytadiene, β-caryophyllene, stigmasterol, γ-sitosterol, and lup-20(29)-en-3-one have contributed to the strong α-glucosidase inhibitory activity of n-Hexane extract of Merremia vitifolia leaves.