Intestinal Glucose Transport Research Articles

Do Compensatory Changes Occur in Intestinal Glucose Transport Following Gastric Bypass in Type 2, Diabetic Rats

Although there is a considerable amount of evidence in the literature showing that Rouen‐en‐Y‐Gastric Bypass (RYGB) in particular, is very effective in resolving Type 2, Diabetes (T2D), a very fundamental question that has not yet been addressed is how transmural glucose transport is modified across the newly configured anatomy of the upper intestinal segments following RYGB? Thus, the objective of the study was to examine potential adaptations in glucose transport across the Roux Limb and distal ileum of ZDF (Zucker Diabetic Fatty) and ZLC (Zucker Lean Control) rats following RYGBUnidirectional glucose fluxes were measured in Ussing chambers under symmetrical, short‐circuited conditions in vitro ~ 10 weeks following the surgical procedure. Segments that were removed included ~ 4 cm of proximal Roux Limb measured from the stomach pouch insertion point; a segment ~ 4 cm at the location measured 35 cm from the ileo‐caecal valve and representing the “predestined” Roux limb in control rats; and a similar size segment immediately proximal to the ileocaecal valve which is the most distal ileum that is not reconfigured in any animal. Using radio‐labeled [14C]‐3‐0‐methylglucose, unidirectional fluxes of glucose were measured across paired adjacent tissues from the mucosal to serosal bath, Jms (absorptive component) and in the opposite direction from serosal to mucosal, Jsm (secretory component) over a 45 min time period. The overall net transport of glucose (Jnet) was determined by subtracting the two unidirectional fluxes. Both the short‐circuit current (Isc) and the transepithelial voltage generated by the tissue is recorded at 15 min intervals and tissue conductance (GT) is calculated from these electrical parameters using Ohm's Law.Major changes in glucose fluxes occurred in obese ZDF/RYGB rats compared to ZDF controls in both of the intestinal segments examined. The unidirectional glucose fluxes are dramatically reduced in RYGB rats and the direction of net glucose transport is reversed across the Roux Limb. It is also notable that tissue conductance of the Roux Limb is reduced by ~ 48% (from GT of 12.0 ± 2.2 mS.cm‐2 in n=8 “predestined” Roux Limb tissues to GT = 6.2 ± 1.3 mS.cm‐2, n=6 Roux Limb tissues) consistent with the lowering (~40% in Jms and ~95% in Jsm) of both unidirectional glucose fluxes indicating an adaptive change in overall tissue permeability. A significant reduction (~82%) occurred in net glucose absorption across the ZDF/RYGB distal ileum (which is not surgically re‐configured) largely via a 64% reduction in Jms. The “predestined” Roux limb of the lean ZLC rats supports a very robust net absorption of glucose that is completely abolished in the reconfigured ZLC/RYGB limb and the unidirectional fluxes were greatly diminished (~90% in Jms and ~70% in Jsm) as was GT from 14.5 ± 2.8 mS.cm‐2 in n=4 “predestined” Roux Limb tissues to GT = 8.0 ± 1.1 mS.cm‐2, n=4 Roux Limb tissues) which is a very similar response to that observed in the obese ZDF rats. There were also major alterations in glucose fluxes across the distal ileum of the lean ZLC/RYGB rats which supported a robust net secretion compared to a net absorption in the lean ZLC controls and no change in GT. To our knowledge, these are the first measurements of intestinal glucose transport in ZDF rats with/without RYGB. In conclusion, we are proposing that altered intestinal handling of glucose may be contributing to the resolution of T2D post RYGB.Support or Funding InformationDK089000

Inclusion of 100% Concord grape juice reduces glucose release following in vitro digestion of a model carbohydrate rich meal

Growing evidence suggest that phenolics from fruits and juices including 100% grape juice (GJ) may impact glucose homeostasis by independently inhibiting carbohydrate digestion and modulating intestinal glucose transport. However, the extent to which these effects are extendable to 100% GJ in the context of interaction within a meal remains unclear. To determine the influence of 100% GJ from purple American grapes (V. labrusca; Concord) on starch digestion and intestinal glucose release from a meal, GJ was combined (5 and 10% w/w) with a milk and cornstarch‐based pudding (MSP) providing protein and complex carbohydrates simulating a meal. This combination was introduced to an in vitro digestion model mimicking oral, gastric and small intestinal digestion. Phenolic bioaccessibility and extent of glucose release from starch were assessed following digestion. Concord GJ is rich in phenolic acids and flavonoids (806 to 845 μM total phenolics) including catechin, quercetin and isorhameritin, as well as anthocyanins (80 to 103 μM total anthocyanins) with cyanidin and delphinidin most abundant. Co‐digestion of GJ with MSP did not significantly impact bioaccessibility of total phenolics suggesting the food matrix did not impact digestive stability and ultimate bioaccessibility in the GI tract. Total glucose content in final digesta was decreased by 12% following co‐digestion of MSP with 10% Concord GJ (~55 μM phenolics) compared to sugar match control. No significant effect was observed from 5% Concord GJ. GJ phenolic extracts also demonstrated modest inhibition of a‐amylase at 500 μM phenolics (3.4–8.8%) and of glucoamylase activity at 300 and 500 μM phenolics (4.9 and 9.3%, respectively). Combined these data suggest that consumption of 100% GJ, compared to a sugar sweetened beverage, with a carbohydrate‐rich meal may delay digestive release of glucose in the upper GI through inhibition of glucoamylase leading to a modest reduction in glycemic response from a meal.Support or Funding InformationFunding support by Welch Foods

Oat β-glucan depresses SGLT1- and GLUT2-mediated glucose transport in intestinal epithelial cells (IEC-6)

Oat β-glucan consumption is linked to reduced risk factors associated with diabetes and obesity by lowering glycemic response and serum level of low-density lipoproteins. The purpose of this study was to identify the mechanism of action of oat β-glucan at the interface between the gut wall and the lumen responsible for attenuating glucose levels. We proposed that viscous oat β-glucan acts as a physical barrier to glucose uptake in normally absorptive gut epithelial cells IEC-6 by affecting the expression of intestinal glucose transporters. Concentration and time-dependent changes in glucose uptake were established by using a nonmetabolizable glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose. The effectiveness of nutrient transport in IEC-6 cells was shown by significant differences in glucose uptake and corresponding transporter expression. The expressions of glucose transporters sodium-glucose–linked transport protein 1 (SGLT1) and glucose transporter 2 (GLUT2) increased with time (0-60 minutes) and glucose levels (5-25 mmol/L). The suppression of glucose uptake and SGLT1 and GLUT2 expression by increasing concentrations (4-8 mg/mL) of oat β-glucan demonstrated a direct effect of the physical properties of oat β-glucan on glucose transport. These results affirmed oat β-glucan as a dietary agent for minimizing postprandial glucose and showed that modulating the activity of the key intestinal glucose transporters with oat β-glucan could be an effective way of lowering blood glucose levels in patients with diabetes.

Chlorogenic Acid Maintains Glucose Homeostasis through Modulating the Expression of SGLT-1, GLUT-2, and PLG in Different Intestinal Segments of Sprague-Dawley Rats Fed a High-Fat Diet

ObjectiveTo reveal the effects and related mechanisms of chlorogenic acid (CGA) on intestinal glucose homeostasis. MethodsForty male Sprague-Dawley rats were randomly and equally divided into four groups: normal chow (NC), high-fat diet (HFD), HFD with low-dose CGA (20 mg/kg, HFD-LC), and HFD with high-dose CGA (90 mg/kg, HFD-HC). The oral glucose tolerance test was performed, and fast serum insulin (FSI) was detected using an enzyme-linked immunosorbent assay. The mRNA expression levels of glucose transporters (Sglt-1 and Glut-2) and proglucagon (Plg) in different intestinal segments (the duodenum, jejunum, ileum, and colon) were analyzed using quantitative real-time polymerase chain reaction. SGLT-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using immunofluorescence. ResultsAt both doses, CGA ameliorated the HFD-induced body weight gain, maintained FSI, and increased postprandial 30-min glucagon-like peptide 1 secretion. High-dose CGA inhibited the HFD-induced elevation in Sglt-1 expression. Both CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal segments. ConclusionAn HFD can cause a glucose metabolism disorder in the rat intestine and affect body glucose homeostasis. CGA can modify intestinal glucose metabolism by regulating the expression of intestinal glucose transporters and Plg, thereby controlling the levels of blood glucose and insulin to maintain glucose homeostasis.

Nutrient-intake-level-dependent regulation of intestinal development in newborn intrauterine growth-restricted piglets via glucagon-like peptide-2

The objective of the present study was to investigate the intestinal development of newborn intrauterine growth-restricted (IUGR) piglets subjected to normal nutrient intake (NNI) or restricted nutrient intake (RNI). Newborn normal birth weight (NBW) and IUGR piglets were allotted to NNI or RNI levels for 4 weeks from day 8 postnatal. IUGR piglets receiving NNI had similar growth performance compared with that of NBW piglets. Small intestine length and villous height were greater in IUGR piglets fed the NNI than that of piglets fed the RNI. Lactase activity was increased in piglets fed the NNI compared with piglets fed the RNI. Absorptive function, represented by active glucose transport by the Ussing chamber method and messenger RNA (mRNA) expressions of two main intestinal glucose transporters, Na+-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), were greater in IUGR piglets fed the NNI compared with piglets fed the RNI regimen. The apoptotic process, characterized by caspase-3 activity (a sign of activated apoptotic cells) and mRNA expressions of p53 (pro-apoptotic), bcl-2-like protein 4 (Bax) (pro-apoptotic) and B-cell lymphoma-2 (Bcl-2) (anti-apoptotic), were improved in IUGR piglets fed the NNI regimen. To test the hypothesis that improvements in intestinal development of IUGR piglets fed NNI might be mediated through circulating glucagon-like peptide-2 (GLP-2), GLP-2 was injected subcutaneously to IUGR piglets fed the RNI from day 8 to day 15 postnatal. Although the intestinal development of IUGR piglets fed the RNI regimen was suppressed compared with those fed the NNI regimen, an exogenous injection of GLP-2 was able to bring intestinal development to similar levels as NNI-fed IUGR piglets. Collectively, our results demonstrate that IUGR neonates that have NNI levels could improve intestinal function via the regulation of GLP-2.

Sodium-Glucose Cotransporter Inhibitors: Effects on Renal and Intestinal Glucose Transport: From Bench to Bedside.

Type 2 diabetes is a chronic disease with disabling micro- and macrovascular complications that lead to excessive morbidity and premature mortality. It affects hundreds of millions of people and imposes an undue economic burden on populations across the world. Although insulin resistance and insulin secretory defects play a major role in the pathogenesis of hyperglycemia, several other metabolic defects contribute to the initiation/worsening of the diabetic state. Prominent among these is increased renal glucose reabsorption, which is maladaptive in patients with diabetes. Instead of an increase in renal glucose excretion, which could ameliorate hyperglycemia, there is an increase in renal glucose reabsorption, which helps sustain hyperglycemia in patients with diabetes. The sodium-glucose cotransporter (SGLT) 2 inhibitors are novel antidiabetes agents that inhibit renal glucose reabsorption and promote glucosuria, thereby leading to reductions in plasma glucose concentrations. In this article, we review the long journey from the discovery of the glucosuric agent phlorizin in the bark of the apple tree through the animal and human studies that led to the development of the current generation of SGLT2 inhibitors.

Effect of White Kidney Beans (Phaseolus vulgaris L. var. Beldia) on Small Intestine Morphology and Function in Wistar Rats.

The chronic ingestion of raw or undercooked kidney beans (Phaseolus vulgaris L.) causes functional and morphological derangement in various tissues. The major objectives of this study were to investigate the gavage effects of a raw Beldia bean variety that is widely consumed in Tunisia, on the small intestine morphology and jejunal absorption of water, electrolytes, and glucose in Wistar rats. Twenty young male rats were randomly divided into two groups of 10 rats. The first group served as the control and was gavaged with 300 mg of a rodent pellet flour suspension (RPFS), whereas the second experimental group was challenged with 300 mg of a Beldia bean flour suspension (BBFS) for 10 days. Histological studies were performed using light and electron microcopy. The intestinal transport of water, sodium, potassium, and glucose was studied by perfusing the jejunal loops of the small bowels in vivo. The feeding experiments indicated that BBFS did not affect weight gain. Histomorphometric analyses showed that the villus heights, crypt depths, and crypt/villus ratios in the jejunum and ileum were greater in the BBFS-fed rats than controls. Electron microscopy studies demonstrated that the rats exposed to RPFS exhibited intact intestinal tracts; however, the BBFS-treated rats demonstrated intestinal alterations characterized by abnormal microvillus architectures, with short and dense or long and slender features, in addition to the sparse presence of vesicles near the brush border membrane. BBFS administration did not significantly affect glucose absorption. However, significant decreases were observed in water and electrolyte absorption compared with the uptake of the controls. In conclusion, raw Beldia beans distorted jejunum morphology and disturbed hydroelectrolytic flux.

Involvement of the Niacin Receptor GPR109a in the LocalControl of Glucose Uptake in Small Intestine of Type 2Diabetic Mice.

Niacin is a popular nutritional supplement known to reduce the risk of cardiovascular diseases by enhancing high-density lipoprotein levels. Despite such health benefits, niacin impairs fasting blood glucose. In type 2 diabetes (T2DM), an increase in jejunal glucose transport has been well documented; however, this is intriguingly decreased during niacin deficient state. In this regard, the role of the niacin receptor GPR109a in T2DM jejunal glucose transport remains unknown. Therefore, the effects of diabetes and high-glucose conditions on GPR109a expression were studied using jejunal enterocytes of 10-week-old m+/db and db/db mice, as well as Caco-2 cells cultured in 5.6 or 25.2 mM glucose concentrations. Expression of the target genes and proteins were quantified using real-time polymerase chain reaction (RT-PCR) and Western blotting. Glucose uptake in Caco-2 cells and everted mouse jejunum was measured using liquid scintillation counting. 10-week T2DM increased mRNA and protein expression levels of GPR109a in jejunum by 195.0% and 75.9%, respectively, as compared with the respective m+/db control; high-glucose concentrations increased mRNA and protein expression of GPR109a in Caco-2 cells by 130.2% and 69.0%, respectively, which was also confirmed by immunohistochemistry. In conclusion, the enhanced GPR109a expression in jejunal enterocytes of T2DM mice and high-glucose treated Caco-2 cells suggests that GPR109a is involved in elevating intestinal glucose transport observed in diabetes.

Aqueous Extract of Nypa fruticans Wurmb. Vinegar Alleviates Postprandial Hyperglycemia in Normoglycemic Rats.

Nypa fruticans Wurmb. vinegar, commonly known as nipa palm vinegar (NPV) has been used as a folklore medicine among the Malay community to treat diabetes. Early work has shown that aqueous extract (AE) of NPV exerts a potent antihyperglycemic effect. Thus, this study is conducted to evaluate the effect of AE on postprandial hyperglycemia in an attempt to understand its mechanism of antidiabetic action. AE were tested via in vitro intestinal glucose absorption, in vivo carbohydrate tolerance tests and spectrophotometric enzyme inhibition assays. One mg/mL of AE showed a comparable outcome to the use of phloridzin (1 mM) in vitro as it delayed glucose absorption through isolated rat jejunum more effectively than acarbose (1 mg/mL). Further in vivo confirmatory tests showed AE (500 mg/kg) to cause a significant suppression in postprandial hyperglycemia 30 min following respective glucose (2 g/kg), sucrose (4 g/kg) and starch (3 g/kg) loadings in normal rats, compared to the control group. Conversely, in spectrophotometric enzymatic assays, AE showed rather a weak inhibitory activity against both α-glucosidase and α-amylase when compared with acarbose. The findings suggested that NPV exerts its anti-diabetic effect by delaying carbohydrate absorption from the small intestine through selective inhibition of intestinal glucose transporters, therefore suppressing postprandial hyperglycemia.

Extracts and flavonoids from onion inhibit the intestinal sodium-coupled glucose transporter 1 (SGLT1) in vitro but show no anti-hyperglycaemic effects in vivo in normoglycaemic mice and human volunteers

Extracts and flavonoids from onion are described as having anti-diabetic activities. We here demonstrate that an onion extract and individual flavonoids thereof diminish glucose uptake mediated by the intestinal glucose transporter SGLT1 when expressed in oocytes and studied in mouse intestinal segments in vitro. Strongest inhibition of SGLT1 was observed for quercetin-4′-O-glucoside (Q4′glc) in oocytes but with only moderate inhibition in jejunal segments of mice. An oral glucose tolerance test (OGTT) performed in obese/hyperglycaemic mice revealed that the onion extract to reduce blood glucose increases significantly. However, an OGTT performed in healthy volunteers after administration of the onion extract failed to reveal an effect on glucose and insulin levels. Despite its capability to inhibit intestinal glucose uptake via SGLT1 in vitro and in mice in vivo, the onion extract did not alter blood glucose levels during an OGTT in human volunteers and this may predominantly be due to a dosing effect.

Ontogenic Changes of Villus Growth, Lactase Activity, and Intestinal Glucose Transporters in Preterm and Term Born Calves with or without Prolonged Colostrum Feeding.

Oral glucose supply is important for neonatal calves to stabilize postnatal plasma glucose concentration. The objective of this study was to investigate ontogenic development of small intestinal growth, lactase activity, and glucose transporter in calves (n = 7 per group) that were born either preterm (PT; delivered by section 9 d before term) or at term (T; spontaneous vaginal delivery) or spontaneously born and fed colostrum for 4 days (TC). Tissue samples from duodenum and proximal, mid, and distal jejunum were taken to measure villus size and crypt depth, protein concentration of mucosa and brush border membrane vesicles (BBMV), total DNA and RNA concentration of mucosa, mRNA expression and activity of lactase, and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1) and facilitative glucose transporter 2 (GLUT2) in mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and immunochemical localization of GLUT2 in the enterocytes were determined. Villus height in distal jejunum was lower in TC than in T. Crypt depth in all segments was largest and the villus height/crypt depth ratio in jejunum was smallest in TC calves. Concentration of RNA was highest in duodenal mucosa of TC calves, but neither lactase mRNA and activity nor SGLT1 and GLUT2 mRNA and protein expression differed among groups. Localization of GLUT2 in the apical membrane was greater, whereas in the basolateral membrane was lower in TC than in T and PT calves. Our study indicates maturation processes after birth for mucosal growth and trafficking of GLUT2 from the basolateral to the apical membrane. Minor differences of mucosal growth, lactase activity, and intestinal glucose transporters were seen between PT and T calves, pointing at the importance of postnatal maturation and feeding for mucosal growth and GLUT2 trafficking.

Potato Phenolics Modulate Rate of Glucose Transport in a Caco‐2 Human Intestinal Cell Model

Potatoes are a rich source of phenolic compounds. While there is evidence for beneficial effects of some phenolics to modulate carbohydrate digestion and glycemic response, the effects of potato phenolics on these responses is not known. The objectives of this study were to characterize the phenolic profile of fresh potatoes (purple, red, or white; 2 varieties each) and finished potato chips and to examine the potential for potato phenolic extracts (PPE) to modulate starch digestion and intestinal glucose transport. We hypothesized that PPEs would inhibit in vitro α‐amylase and α‐glucosidase activity and decrease rate of d7‐glucose transport in a Caco‐2 human intestinal cell model. PPEs were found to be rich in anthocyanins (98, 11 and 0 mg/100 g dw) and chlorogenic acids (519, 425 and 157 mg/100 g dw) for purple, red and white varieties respectively. While no significant effects were observed on starch digestion, PPEs (from whole potato and peel) were found to significantly (p<0.05) decrease the rate of glucose transport over a 60 min period by 4.50‐83.89% (3.0µmoles/min for d7‐glucose control relative to 0.48‐2.21 µmoles/min for PPEs). Furthermore, PPEs at 100 μM were found to decrease 60 min transport of d7‐glucose by 11.81‐83.64% relative to d7‐glucose controls. These results suggest that potato phenolics merit further consideration as bioactive agents that may affect rate of intestinal glucose transport. Funding provided by Pepsico Global R&D.

Glucose transporters: cellular links to hyperglycemia in insulin resistance and diabetes.

Abnormal expression and/or function of mammalian hexose transporters contribute to the hallmark hyperglycemia of diabetes. Due to different roles in glucose handling, various organ systems possess specific transporters that may be affected during the diabetic state. Diabetes has been associated with higher rates of intestinal glucose transport, paralleled by increased expression of both active and facilitative transporters and a shift in the location of transporters within the enterocyte, events that occur independent of intestinal hyperplasia and hyperglycemia. Peripheral tissues also exhibit deregulated glucose transport in the diabetic state, most notably defective translocation of transporters to the plasma membrane and reduced capacity to clear glucose from the bloodstream. Expression of renal active and facilitative glucose transporters increases as a result of diabetes, leading to elevated rates of glucose reabsorption. However, this may be a natural response designed to combat elevated blood glucose concentrations and not necessarily a direct effect of insulin deficiency. Functional foods and nutraceuticals, by modulation of glucose transporter activity, represent a potential dietary tool to aid in the management of hyperglycemia and diabetes.

The effect of oat β‐glucan on in vitro glucose diffusion and glucose transport in rat small intestine

Many previous studies have reported the role of oat β-glucan (OBG) in the reduction of postprandial glucose, and hypothesised that OBG may form a protective layer along the intestinal wall, acting as a viscous barrier to decrease glucose transportation. This study examined whether the molecular weight (MW) and concentration of OBG affected the diffusion of glucose in vitro. The effect of OBG on glucose transportation in vitro and sodium-potassium adenosine triphosphatase (Na(+)/K(+)-ATPase) activity in the everted small intestines of normal rats was also examined. In vitro, higher MWs and concentrations of OBG increased the inhibitory effects on glucose diffusion and glucose adsorption. The transport of glucose by glucose transporters and Na(+)/K(+)-ATPase activity in the small intestinal mucosa of rats were significantly lower following the addition of OBG than those in the absence of OBG at the same time-points throughout glucose transportation (P < 0.05). In the OBG-treated group, the Na(+)/K(+)-ATPase activity decreased with increasing OBG MW. However, as the concentration of OBG in the solution increased, the Na(+)/K(+)-ATPase activity in the small intestine increased due to stronger gastrointestinal motility. We also found that higher MWs of OBG had a greater inhibitory effect on intestinal disaccharidase activities in vitro. Oat β-glucan is able to adsorb glucose molecules, inhibit glucose transport, decrease the concentration of available glucose and suppress disaccharidase activities in the small intestine.

Effects of Salmon Nasal Cartilage Proteoglycan on Plasma Glucose Concentration and Active Glucose Transport in the Small Intestine

Recently, proteoglycan was purified from the nasal cartilage of salmon. Although several physiological effects have been reported, the effect of salmon nasal cartilage proteoglycan (salmon PG) on glucose metabolism remains unclear. We studied the effect of salmon PG on rat plasma glucose levels. Oral administration of 1% salmon PG significantly attenuated the increase in portal plasma glucose levels following an oral glucose tolerance test (OGTT). Additionally 1% salmon PG delayed the increase in peripheral glucose concentration induced by the OGTT. Mucosal administration of 1% salmon PG significantly decreased active glucose transport using the everted jejunal sac method. Furthermore, transmural potential difference (ΔPD) measurements using the everted jejunum revealed that 1% salmon PG significantly decreased glucose-dependent and phlorhizin (inhibitor of sodium-glucose co-transporter 1; SGLT1)-sensitive ΔPD. These results suggest that salmon PG decreases glucose absorption via SGLT1 in the jejunum, thereby attenuating the increase in portal and peripheral plasma glucose levels in rats.

The impact of heat stress on intestinal function and productivity in grow-finish pigs

Heat stress is a physiological condition when animals can no longer regulate their internal euthermic temperature. When livestock such as pigs are subjected to this environmental stress, it can be detrimental to performance, health and well-being, and if severe enough even death. Growing pigs are particularly susceptible to heat stress and one of the major organs first affected by heat stress is the gastrointestinal tract. As a result, reductions in appetite, intestinal function and integrity and increased risk of endotoxemia can modify post-absorptive metabolism and tissue accretion. These changes in intestinal integrity may be a result of altered expression of tight junction proteins, increased circulating endotoxin concentrations and markers of cellular stress (heat shock and hypoxia response), which is evident as early on as 2 h after heat-stress onset. Due to restricted blood flow, the ileum is more severely affected compared with the colon. Interestingly, many of the negative effects of heat stress on intestinal integrity appear to be similar to those observed with pigs reared under reduced nutrient and caloric intakes. Altogether, these depress pig performance and health, and extend days to market. Despite this impact on the gastrointestinal tract, under heat-stress conditions, intestinal glucose transport pathways are upregulated. This review discussed how heat stress (directly and indirectly via reduced feed intake) affects intestinal integrity and how heat stress contributes to decreased growth performance in growing pigs.

Estriol blunts postprandial blood glucose rise in male rats through regulating intestinal glucose transporters.

Despite increased total food intake in healthy, late-stage pregnant women, their peak postprandial blood sugar levels are normally much lower than the levels seen in healthy nonpregnant women. In this study, we sought to determine whether estriol (E3), an endogenous estrogen predominantly produced during human pregnancy, contributes to the regulation of the postprandial blood glucose level in healthy normal rats. In vivo studies using rats showed that E3 blunted the speed and magnitude of the blood glucose rise following oral glucose administration, but it did not appear to affect the total amount of glucose absorbed. E3 also did not affect insulin secretion, but it significantly reduced the rate of intestinal glucose transport compared with vehicle-treated animals. Consistent with this finding, expression of the sodium-dependent glucose transporter 1 and 2 was significantly downregulated by E3 treatment in the brush-border membrane and basolateral membrane, respectively, of enterocytes. Most of the observed in vivo effects were noticeably stronger with E3 than with 17β-estradiol. Using differentiated human Caco-2 enterocyte monolayer culture as an in vitro model, we confirmed that E3 at physiologically relevant concentrations could directly inhibit glucose uptake via suppression of glucose transporter 2 expression, whereas 17β-estradiol did not have a similar effect. Collectively, these data showed that E3 can blunt the postprandial glycemic surge in rats through modulating the level of intestinal glucose transporters.

Obesity and the gastrointestinal tract: you are what you eat.

Obesity represents a complex multifactorial syndrome that develops from interactions among genetic and environmental factors and is a leading cause of illness and death. The prevalence of obesity in the United States has increased dramatically since 1975. Although often ignored, the gastrointestinal tract, and the gastrointestinal regulatory peptides in particular, constitutes an ideal starting point for defining and investigating obesity as it represents the route by which all nutrients are ingested, processed, and absorbed. Another important factor to consider when evaluating the etiology of obesity is the capacity for all animals to store nutrients. Insulin is the most potent anabolic hormone, and it appears to have evolved from the need to maximize energy efficiency, obviating the requirement to continuously forage for food. Organisms expressing this important peptide possessed a distinct survival advantage and flourished. During the course of evolution, insulin biosynthesis translocated from the intestine to pancreatic islets, which necessitated a messenger from the intestine to complete the "enteroinsular axis." The eventual development of glucose-dependent insulinotropic polypeptide (GIP) and other incretins fulfilled this requirement. GIP appears to offer an additional survival benefit by not only stimulating intestinal glucose transport and maximally releasing insulin to facilitate nutrient storage but also by its insulin-mimetic properties, including enhanced uptake of glucose by adipocytes. This physiological redundancy offered by insulin and GIP ensured the survival of organisms during times when food was scarce. As food is no longer scarce, at least in the West, this survival advantage appears to have contributed to the current obesity epidemic.

Acute activation of cannabinoid receptors by anandamide reduces gastrointestinal motility and improves postprandial glycemia in mice.

The endocannabinoid system (ECS) is associated with an alteration of glucose homeostasis dependent on cannabinoid receptor-1 (CB1R) activation. However, very little information is available concerning the consequences of ECS activation on intestinal glucose absorption. Mice were injected intraperitoneally with anandamide, an endocannabinoid binding both CB1R and CB2R. We measured plasma glucose and xylose appearance after oral loading, gastrointestinal motility, and glucose transepithelial transport using the everted sac method. Anandamide improved hyperglycemia after oral glucose charge whereas glucose clearance and insulin sensitivity were impaired, pointing out some gastrointestinal events. Plasma xylose appearance was delayed in association with a strong decrease in gastrointestinal transit, while anandamide did not alter transporter-mediated glucose absorption. Interestingly, transit was nearly normalized by coinjection of SR141716 and AM630 (CB1R and CB2R antagonist, respectively), and AM630 also reduced the delay of plasma glucose appearance induced by anandamide. When gastric emptying was bypassed by direct glucose administration in the duodenum, anandamide still reduced plasma glucose appearance in wild-type but not in CB1R(-/-) mice. In conclusion, our findings demonstrated that acute activation of intestinal ECS reduced postprandial glycemia independently on intestinal glucose transport but rather inhibiting gastric emptying and small intestine motility and strongly suggest the involvement of both CB1R and CB2R.

Clostridium ramosum promotes high-fat diet-induced obesity in gnotobiotic mouse models.

ABSTRACTThe intestines of obese humans and mice are enriched with Erysipelotrichi, a class within the Firmicutes. Clostridium ramosum, a member of the Erysipelotrichi, is associated with symptoms of the metabolic syndrome in humans. To clarify the possible obesogenic potential of this bacterial species and to unravel the underlying mechanism, we investigated the role of C. ramosum in obesity development in gnotobiotic mice. Mice were associated with a simplified human intestinal (SIHUMI) microbiota of eight bacterial species, including C. ramosum, with the SIHUMI microbiota except C. ramosum (SIHUMIw/oCra), or with C. ramosum only (Cra) and fed a high-fat diet (HFD) or a low-fat diet (LFD). Parameters related to the development of obesity and metabolic diseases were compared. After 4 weeks of HFD feeding, the mouse groups did not differ in energy intake, diet digestibility, gut permeability, and parameters of low-grade inflammation. However, SIHUMI and Cra mice fed the HFD gained significantly more body weight and body fat and displayed higher food efficiency than SIHUMIw/oCra mice fed the HFD. Gene expression of glucose transporter 2 (Glut2) in jejunal mucosa and of fatty acid translocase (CD36) in ileal mucosa was significantly increased in the obese SIHUMI and Cra mice compared with the less obese SIHUMIw/oCra mice. The data demonstrate that the presence of C. ramosum in SIHUMI and Cra mice enhanced diet-induced obesity. Upregulation of small intestinal glucose and fat transporters in these animals may contribute to their increased body fat deposition.