Glucose Tolerance In Rats Research Articles

Characterization of Turner Syndrome-associated diabetes mellitus.

Diabetes mellitus (DM) risk factors in Turner Syndrome (TS) may include autoimmunity, obesity, beta-cell dysfunction, genetic predisposition and insulin resistance (IR). Evaluate glucose tolerance and DM risk factors in adults with TS. A single centre study with two phases. To determine the prevalence of DM and to assess diabetes risk markers comparing women with TS with and without impaired glucose tolerance (IGT). Tertiary referral center, University College Hospitals. 106 Women with TS (age range 18-70 years) undergoing annual health surveillance. Participants underwent oral glucose tolerance tests (OGTT), with additional samples for autoimmunity and genetic analysis. Glucose tolerance, insulin, autoimmune and single nucleotide polymorphism (SNP) profile. OGTT screening showed that those without a previous DM diagnosis, 72.7% had normal glucose tolerance, 19.5% had IGT, and 7.6% were newly diagnosed with DM. OGTT identified more cases of DM than HbAc1 sampling alone. Women with IGT or DM were older, with higher body mass index and IR. No association was found between autoimmune markers GAD, IA-2 and ZnT8, risk karyotypes or selected SNPs and DM. In DM cases, GAD positivity was associated with requirement for insulin therapy. The median age of onset of the diagnosis of DM was 36 years (range 11-56). In the spectrum of DM subtypes, TS-associated DM lies between type 1 and type 2 DM with features of both. Key factors include weight and IR. Assessing C-peptide or GAD antibodies may aid future insulin requirement.

Small intestinal CaSR-dependent and CaSR-independent protein sensing regulates feeding and glucose tolerance in rats.

Proteins activate small intestinal calcium sensing receptor (CaSR) and/or peptide transporter 1 (PepT1) to increase hormone secretion1-8, but the effect of small intestinal protein sensing and the mechanistic potential of CaSR and/or PepT1 in feeding and glucose regulation remain inconclusive. Here we show that, in male rats, CaSR in the upper small intestine is required for casein infusion to increase glucose tolerance and GLP1 and GIP secretion, which was also dependent on PepT1 (ref. 9). PepT1, but not CaSR, is required for casein infusion to lower feeding. Upper small intestine casein sensing fails to regulate feeding, but not glucose tolerance, in high-fat-fed rats with decreased PepT1 but increased CaSR expression. In the ileum, a CaSR-dependent but PepT1-independent pathway is required for casein infusion to lower feeding and increase glucose tolerance in chow-fed rats, in parallel with increased PYY and GLP1 release, respectively. High fat decreases ileal CaSR expression and disrupts casein sensing on feeding but not on glucose control, suggesting an ileal CaSR-independent, glucose-regulatory pathway. In summary, we discover small intestinal CaSR- and PepT1-dependent and -independent protein sensing mechanisms that regulate gut hormone release, feeding and glucose tolerance. Our findings highlight the potential of targeting small intestinal CaSR and/or PepT1 to regulate feeding and glucose tolerance.

Single anastomosis duodeno-ileal bypass with sleeve gastrectomy generates sustained improvement of glycemic control compared with sleeve gastrectomy in the diet-induced obese rat model.

Bariatric surgery has become a recognized and effective procedure for treating obesity and type 2 diabetes (T2D). Our objective was to directly compare the caloric intake-independent effects of sleeve gastrectomy (SG) and single anastomosis duodenoileal bypass with SG (SADI-S) on glucose tolerance in rats with diet-induced obesity (DIO) and to elucidate the differences between bariatric surgery and caloric restriction.A total of 120 adult male Wistar rats with DIO and insulin resistance were randomly assigned to surgical (sham operation, SG, and SADI-S) and dietary (pair-feeding the amount of food eaten by animals undergoing the SG or SADI-S surgeries) interventions. Body weight and food intake were weekly monitored, and 6weeks after interventions, fasting plasma glucose, oral glucose and insulin tolerance tests, plasma insulin, adiponectin, GIP, GLP-1, and ghrelin levels were determined.The body weight of SADI-S rats was significantly (p < 0.001) lower as compared to the sham-operated, SG, and pair-fed groups. Furthermore, SADI-S rats exhibited decreased whole body fat mass (p < 0.001), lower food efficiency rates (p < 0.001), and increased insulin sensitivity, as well as improved glucose and lipid metabolism compared to that of the SG and pair-fed rats.SADI-S was more effective than SG, or caloric restriction, in improving glycemic control and metabolic profile, with a higher remission of insulin resistance as well as long-term weight loss.

Influence of maternal hyperglycemia on rat daughters and granddaughters

This study evaluated the influence of maternal diabetes on the reproductive outcomes of adult daughters during full-term pregnancy in rats. The local ethics committee approved all experimental protocols. The adult female pups of nondiabetic (control – CP) and diabetic (DP) mothers were subjected to mating with healthy male rats for reproductive analysis. On day 17 of pregnancy, both groups underwent an oral glucose tolerance test (OGTT) to evaluate glucose tolerance. At the end of pregnancy, the rats were anesthetized for laparotomy and exposure of maternal organs. Uterine horns, ovaries, fetuses, and placentas were weighed to classify fetal weight and placental efficiency. P&lt;0.05 was considered a statistically significant limit, and Pearson's correlation was used. Higher maternal fasting blood glucose was correlated with a lower number of live fetuses and, consequently, with a lower litter weight. Thus, maternal fasting glucose during pregnancy is a relevant biomarker related to the poor reproductive outcome of daughters of rats. Furthermore, these findings show the detrimental effects of fetal programming induced by maternal diabetes in adulthood in the subsequent generation.

Impact of Plant-Derived Dietary Fibers on Energy and Glucose Homeostasis

The gut microbiota contributes to the development of metabolic disease, and it is well known that diet shapes the gut microbiota, emphasizing the need to better understand how diet impacts metabolic disease via alterations in the gut microbiota. Dietary fiber intake is linked with improvements in metabolic homeostasis in humans, and specific fibers beneficially alter the gut microbiota, promote weight loss, and improve glucose homeostasis. In a previous study, we found that specific plant-based flours, including wheat and barley, supplemented into a high-fat diet (HFD) reduced body weight and adiposity and improved glucose tolerance in rats. However, whether this was due to specific fibers within the flours remains unknown. To test the impact of various dietary fibers on energy and glucose homeostasis, we supplemented HFD-fed mice with 5 different fibers (beta-pectin, beta-glucan, wheat dextrin, resistant starch, or cellulose as a control) at 10% (w/w) for 18 weeks (n=12/group), measuring body weight, adiposity, indirect calorimetry, and glucose tolerance. We found that only beta-glucan supplementation in a HFD decreased adiposity and body weight gain and improved oral glucose tolerance compared to HFD with cellulose, while all other dietary fibers failed to improve metabolic homeostasis. Supplementation with beta-glucan increased energy expenditure and locomotor activity in mice compared to HFD-cellulose. Despite a lack of metabolic effect for most dietary fibers, all fibers supplemented into a HFD shifted the cecal microbiota composition and exhibited increased SCFA levels. However, only beta-glucan supplemented mice specifically exhibited an increase in Ileibacterium relative abundance, as well as higher cecal butyrate levels compared to HFD-cellulose. These findings demonstrate that beta-glucan is a promising therapeutic option for diet-induced obesity and glucose tolerance, possibly via increased energy expenditure. Future studies will investigate the role of the gut microbiota and butyrate in the metabolic improvements observed with beta-glucan supplementation in HFD-feeding. USDA National Institute of Food and Agriculture This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Rosa canina L. improves learning and memory-associated cognitive impairment by regulating glucose levels and reducing hippocampal insulin resistance in high-fat diet/streptozotocin-induced diabetic rats

Ethnopharmacological relevanceRecent studies claim that Type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) overlap in several common pathological pathways which from neuronal damage to impaired memory performance. It is known that the use of Rosa canina L. (R. canina) as medicine in folk medicine dates back to ancient times and is used in the treatment of nervous diseases in Persian medicine. However, the effect of R. canina on diabetes-related cognitive decline and memory impairment has not yet been studied. Aim of the studyWe evaluated the impact of T2DM on AD-like alterations and examined the molecular mechanism of a possible effect of R. canina on cognitive alterations in diabetic rats. Materials&methodsR. canina ethanol extract was obtained by maceration method. This study was performed with male Sprague-Dawley rats fed with a high-fat diet (HFD) for 8 weeks, low-dose streptozotocin (STZ; 35 mg/kg IP) injection for 4 weeks, and R. canina (250 mg/kg; per oral) and metformin (400 mg/kg; per oral) administration for 4 weeks. The weight and blood glucose of rats were measured weekly. To evaluate glucose tolerance area under the curve (AUC) was calculated by performing an oral glucose tolerance test. Then the rats were subjected to behavioural tests, and their hippocampus and cortex tissues were obtained for biochemical and morphological analyses. ResultsR. canina could manage glucose responsiveness by reducing post-prandial blood glucose levels, preventing weight loss, and raising serum insulin levels in T2DM-induced rats. Behavioural tests showed that R. canina significantly improves diabetes-related cognitive decline in recall and long-term memory. Treatment with R. canina significantly reversed HFD/STZ-induced increases in insulin, amyloid-β, amyloid precursor protein levels, and acetylcholinesterase activity in the prefrontal cortex and hippocampus. Furthermore, histological analyzes revealed the protection of R. canina against neuronal disruption in the cortical and hippocampal CA3 region caused by chronic hyperglycemia. ConclusionAnalyzed collectively, these results suggest that R. canina can correct T2DM-related cognitive decline may be attributed to insulin pathway modulation, prevention of amyloid deposition, and increased cholinergic transmission.

Limonin mitigates cardiometabolic complications in rats with metabolic syndrome through regulation of the IRS-1/GLUT4 signalling pathway

Limonin is a natural triterpenoid isolated from citrus fruit. In the present study, we examined the effects of limonin on cardiometabolic alterations in diet-induced metabolic syndrome. Metabolic syndrome was induced in rats by feeding them a high-fat (HF) diet plus 15% fructose in drinking water for 16 weeks. They were treated with limonin (50 or 100 mg/kg) (n = 8/group) for the final 4 weeks. Increases in body weight (BW), fasting blood glucose (FBG), serum insulin, total cholesterol (TC), blood pressure (BP), liver fat accumulation, and adipocyte hypertrophy, as well as oral glucose tolerance in rats with metabolic syndrome were alleviated by limonin treatment (p < 0.05). Limonin improved ejection fraction and left ventricular (LV) hypertrophy, and reduced angiotensin converting enzyme (ACE) activity and angiotensin II (Ang II) concentration in rats with metabolic syndrome (p < 0.05). It also reduced plasma tumour necrosis factor (TNF)-α, interleukin (IL)− 6, leptin, malonaldehyde (MDA), and superoxide generation, and increased catalase activity in rats with metabolic syndrome compared to controls (p < 0.05). Downregulation of insulin receptor substrate 1 (IRS-1) and glucose transporter type 4 (GLUT4) protein expression in epididymal fat pads and cardiac, liver, and gastrocnemius tissues was present in metabolic syndrome, and these were restored by limonin treatment (p < 0.05). In conclusion, limonin shows a potential effect in alleviating symptoms and improving cardiometabolic disorders. These beneficial effects are linked to the reduction of the renin-angiotensin system, inflammation, oxidative stress, and improvement of IRS-1/GLUT4 protein expression in the target tissue.

CARBOHYDRATES METABOLISM IN THE BLOOD OF RATS WITH IMPAIRED GLUCOSE TOLERANCE UNDER LONG TERM MELATONIN INJECTIONS.

The aim: To determine the influence of melatonin on the glucose level and content of malondialdehyde, activities of pyruvate kinase and glucose-6-phosphate dehydrogenase enzymes in the blood; histochemical features of glycogen distribution in liver of rats with impaired glucose tolerance. Materials and methods: Diabetes in rats was induced by intra-abdominal injection of a 5% solution of alloxan monohydrate at the rate of 170 mg/kg of body weight. Four days after animals were divided into rats with impaired glucose tolerance and melatonin-group with impaired glucose tolerance (5 mg/ kg «Sigma» USA, daily and intraperitoneal for 42 days starting from 5th day). Impaired glucose tolerance was determined by measurement of glucose profiles - fasting <5.6 mmol/l; postprandial (2h post-load) 7.8 - 11.0 mmol/l. Histochemical examination of the liver was performed according to the standard method of PAS-reaction staining. Statistical analysis was performed using Statistica 10 StatSoft Inc. Results: Pyruvate kinase activity in erythrocytes and optical density of glycogen in hepatocytes of animals with impaired glucose tolerance decreased on 18% and 11%, activity of glucose-6-phosphate dehydrogenase and content of malondialdehyde increased on 35% and 23%, respectively compared with the control. We have reached the recovery of the pyruvate kinase and normalization of glucose-6-phosphate dehydrogenase activities, malondialdehyde levels, glucose profiles in the blood as well as glycogen distribution in the liver caused by melatonin injections. Conclusions: We have determined that long term melatonin injections did better glucose tolerance in rats.

Antidiabetic Effect of Millet Bran Polysaccharides Partially Mediated via Changes in Gut Microbiome.

Diabetes is a type of metabolic disease associated with changes in the intestinal flora. In this study, the regulatory effect of millet bran on intestinal microbiota in a model of type 2 diabetes (T2DM) was investigated in an effort to develop new approaches to prevent and treat diabetes and its complications in patients. The effect of purified millet bran polysaccharide (MBP) with three different intragastric doses (400 mg/kg, 200 mg/kg, and 100 mg/kg) combined with a high-fat diet was determined in a streptozotocin (STZ)-induced model of T2DM. By analyzing the changes in indicators, weight, fasting blood sugar, and other bio-physiological parameters, the changes in gut microbiota were analyzed via high-throughput sequencing to establish the effect of MBP on the intestinal flora. The results showed that MBP alleviated symptoms of high-fat diet-induced T2DM. A high dosage of MBP enhanced the hypoglycemic effects compared with low and medium dosages. During gavage, the fasting blood glucose (FBG) levels of rats in the MBP group were significantly reduced (p &lt; 0.05). The glucose tolerance of rats in the MBP group was significantly improved (p &lt; 0.05). In diabetic mice, MBP significantly increased the activities of CAT, SOD, and GSH-Px. The inflammatory symptoms of liver cells and islet cells in the MBP group were alleviated, and the anti-inflammatory effect was partially correlated with the dose of MBP. After 4 weeks of treatment with MBP, the indices of blood lipid in the MBP group were significantly improved compared with those of the DM group (p &lt; 0.05). Treatment with MBP (400 mg/kg) increases the levels of beneficial bacteria and decreases harmful bacteria in the intestinal tract of rats, thus altering the intestinal microbial community and antidiabetic effect on mice with T2DM by modulating gut microbiota. The findings suggest that MBP is a potential pharmaceutical supplement for preventing and treating diabetes.

Oral administration of zein-based nanoparticles reduces glycemia and improves glucose tolerance in rats

The aim was to evaluate the effect of zein-based nanoparticles on the glucose homeostasis, following oral administration to Wistar rats. For this purpose, bare nanoparticles (NP, with tropism for the upper intestinal regions) and poly(ethylene glycol)-coated nanoparticles (NP-PEG), with the capability to reach the ileum and cecum of animals, were evaluated. Both formulations were spherical in shape, displaying sizes around 200 nm and a negative surface zeta potential. The oral administration of a single dose of these nanoparticles to animals (50 mg/kg) induced a significant decrease of the glycemia, compared control rats and in animals treated with the free protein (p < 0.001). Moreover, these nanoparticles improved the glycemic control against an intraperitoneal glucose tolerance test; particularly NP-PEG. These findings would be due to an increased release of glucagon-like peptide-1 (GLP-1) by l-cells, which are more abundant in distal regions of the intestine. In fact, the GLP-1 blood levels of animals treated with nanoparticles were significantly higher than controls (about 40 % and 60 % for NP and NP-PEG groups, respectively). This higher capability of NP-PEG, with respect to NP, to increase the release of GLP-1 and control glycemia would be related to its ability to reach the distal areas of the small intestine.

Inulin reduces visceral adipose tissue mass and improves glucose tolerance through altering gut metabolites

AimInulin, a soluble dietary fiber, is a source of energy for the host while the metabolites, such as short-chain fatty acids (SCFAs), produced in the gut through bacterial fermentation exerts the anti-obesity effect. In this study, we aimed to apply a metabolomics approach and clarify the role of this soluble dietary fiber on glucose and lipid metabolism under the calorie-matched condition.Materials and methodsEight-week-old male C57BL/6J mice were fed a high-fat/high-sucrose based diet containing maltodextrin or inulin for 12 weeks through calorie-matched pair feeding. We evaluated glucose tolerance, and energy expenditure using indirect calorimetry, comprehensive metabolites in the content of jejunum, feces, and portal vein serum using gas chromatography-mass spectrometry, and histological changes in the adipose tissue.ResultsThe inulin group exhibited reduced visceral adipose tissue and smaller size of visceral adipocyte. It also exhibited improved glucose tolerance and an increase in energy expenditure. Reflecting the results of fermentation, the metabolomics analysis revealed an increase in the succinic acid and SCFA contents in both feces and portal vein serum in the inulin group.ConclusionsInulin altered the gut metabolites and reduced visceral adipose tissue, thereby resulting in improved glucose tolerance.

Structurally-engineered fatty acid 1024 (SEFA-1024) improves diet-induced obesity, insulin resistance, and fatty liver disease.

Obesity is a global epidemic that drives morbidity and mortality through cardiovascular disease, diabetes, and non-alcoholic fatty liver disease (NAFLD). No definitive therapy has been approved to improve glycemic control and treat NAFLD in obese patients. Here, we investigated a semi-synthetic, long chain, structurally-engineered fatty acid-1024 (SEFA-1024), as a treatment for obesity-induced hyperglycemia, insulin-resistance, and fatty liver disease in rodent models. A single dose of SEFA-1024 was administered to evaluate glucose tolerance and active glucagon-like peptide 1 (GLP-1) in lean rats in the presence and absence of a DPP-4 inhibitor. The effects of SEFA-1024 on weight loss and glycemic control were assessed in genetic (ob/ob) and environmental (high-fat diet) murine models of obesity. Liver histology, serum liver enzymes, liver lipidomics, and hepatic gene expression were also assessed in the high-fat diet murine model. SEFA-1024 reversed obesity-associated insulin resistance and improved glycemic control. SEFA-1024 increased active GLP-1. In a long-term model of diet-induced obesity, SEFA-1024 reversed excessive weight gain, hepatic steatosis, elevated liver enzymes, hepatic lipotoxicity, and promoted fatty acid metabolism. SEFA-1024 is an enterohepatic-targeted, eicosapentaenoic acid derivative that reverses obesity-induced dysregulated glucose metabolism and hepatic lipotoxicity in genetic and dietary rodent models of obesity. The mechanism by which SEFA-1024 works may include increasing aGLP-1, promoting fatty acid oxidation, and inhibiting hepatic triglyceride formation. SEFA-1024 may serve as a potential treatment for obesity-related diabetes and NAFLD.

Antidiabetic activity and metabolite profiles of ascidian Halocynthia roretzi

• Consumption of ascidian of H. roretzi tissues significantly improves the glucose tolerance in diabetic rats. • Consumption of ascidian H. roretzi tissue significantly reduces plasma cholesterol and triglyceridesin levels in diabetic rats. • Ascidian H. roretzi tissue is a rich source of amino acid, unsaturated fatty acids, vitamins, and bioactive compounds. • Ascidian H. roretzi tissue contain 11 anti-diabetes molecules and high levels of natural astaxanthin. Halocynthia roretzi has been cultured and utilized as a nutritious seafood in Southeastern Asia for many years because of its abundance active molecules. Here, we reported that feeding of H. roretzi tissues resulted in improving oral glucose tolerance in rats. To screen the active components, we identified 950 chemical compounds from H. roretzi metabolome. Furthermore, 11 molecules with the activity of regulating blood glucose and lipids were selected based on structural identity. Among them, two natural products, hesperetin and astaxanthin were selected for further quantitative detection. The results showed that concentrations of hesperetin and astaxanthin in the tissues of H. roretzi were calculated to be 13.7 ± 9.5 and 167.9 ± 48.4 µg/100 g, respectively. The high content of astaxanthin in H. roretzi indicates its potential roles and functions in anti-diabetes activity. Taken together, our results showed that H. roretzi could be used as a functional food supplement for regulating lipid/glucose metabolism.

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

Antihyperglycemic Effect of Lavandula pedunculata: In Vivo, In Vitro and Ex Vivo Approaches.

Lavandula pedunculata (Mill.) Cav. (LP) is one of lavender species traditionally used in Morocco to prevent or cure diabetes, alone or in the form of polyherbal preparations (PHP). Therefore, the primary objective of this study was to test the antihyperglycemic effect of the aqueous extract of LP, alone and in combination with Punica granatum L. (PG) and Trigonella foenum-graecum L. (FGK). The secondary objective was to explore some mechanisms of action on the digestive functions. The antihyperglycemic effect of the aqueous extract of LP, alone and in combination with PG and FGK, was studied in vivo using an oral glucose tolerance test (OGTT). In addition, LP extract was tested on the activities of some digestive enzymes (pancreatic α-amylase and intestinal α-glucosidase) in vitro and on the intestinal absorption of glucose ex vivo using a short-circuit current (Isc) technique. Acute and chronic oral administration of LP aqueous extract reduced the peak of the glucose concentration (30 min, p < 0.01) and the area under the curve (AUC, p < 0.01). The effect of LP + PG was at the same amplitude to that of the positive control Metformin (MET). LP aqueous extract inhibited the pancreatic α-amylase with an IC50 almost identical to acarbose (0.44 ± 0.05 mg/mL and 0.36 ± 0.02 mg/mL, respectively), as well as the intestinal α-glucosidase, (IC50 = 131 ± 20 µg/mL) and the intestinal glucose absorption (IC50 = 81.28 ± 4.01 µg/mL) in concentration-dependent manners. LP aqueous extract exhibited potent actions on hyperglycemia, with an inhibition on digestive enzymes and glucose absorption. In addition, the combination with PG and FGK enhanced oral glucose tolerance in rats. These findings back up the traditional use of LP in type 2 diabetes treatment and the effectiveness of the alternative and combinative poly-phytotherapy (ACPP).

Coffee Pulp, a By-Product of Coffee Production, Modulates Gut Microbiota and Improves Metabolic Syndrome in High-Carbohydrate, High-Fat Diet-Fed Rats.

Waste from food production can be re-purposed as raw material for usable products to decrease industrial waste. Coffee pulp is 29% of the dry weight of coffee cherries and contains caffeine, chlorogenic acid, trigonelline, diterpenes and fibre. We investigated the attenuation of signs of metabolic syndrome induced by high-carbohydrate, high-fat diet in rats by dietary supplementation with 5% freeze-dried coffee pulp for the final 8 weeks of a 16-week protocol. Coffee pulp decreased body weight, feed efficiency and abdominal fat; normalised systolic blood pressure, left ventricular diastolic stiffness, and plasma concentrations of triglycerides and non-esterified fatty acids; and improved glucose tolerance in rats fed high-carbohydrate, high-fat diet. Further, the gut microbiota was modulated with high-carbohydrate, high-fat diet and coffee pulp supplementation and 14 physiological parameters were correlated with the changes in bacterial community structures. This study suggested that coffee pulp, as a waste from the coffee industry, is useful as a functional food for improving obesity-associated metabolic, cardiovascular and liver structure and function, and gut microbiota.

Intramuscular Injection of miR-1 Reduces Insulin Resistance in Obese Mice.

The role of microRNAs in metabolic diseases has been recognized and modulation of them could be a promising strategy to treat obesity and obesity-related diseases. The major purpose of this study was to test the hypothesis that intramuscular miR-1 precursor replacement therapy could improve metabolic parameters of mice fed a high-fat diet. To this end, we first injected miR-1 precursor intramuscularly in high-fat diet-fed mice and evaluated glucose tolerance, insulin sensitivity, and adiposity. miR-1-treated mice did not lose weight but had improved insulin sensitivity measured by insulin tolerance test. Next, using an in vitro model of insulin resistance by treating C2C12 cells with palmitic acid (PA), we overexpressed miR-1 and measured p-Akt content and the transcription levels of a protein related to fatty acid oxidation. We found that miR-1 could not restore insulin sensitivity in C2C12 cells, as indicated by p-Akt levels and that miR-1 increased expression of Pgc1a and Cpt1b in PA-treated cells, suggesting a possible role of miR-1 in mitochondrial respiration. Finally, we analyzed mitochondrial oxygen consumption in primary skeletal muscle cells treated with PA and transfected with or without miR-1 mimic. PA-treated cells showed reduced basal respiration, oxygen consumption rate-linked ATP production, maximal and spare capacity, and miR-1 overexpression could prevent impairments in mitochondrial respiration. Our data suggest a role of miR-1 in systemic insulin sensitivity and a new function of miR-1 in regulating mitochondrial respiration in skeletal muscle.

Annona muricata L. extract decreases intestinal glucose absorption and improves glucose tolerance in normal and diabetic rats

Introduction: Poorly controlled hyperglycemia causes numerous health complications. Postprandial hyperglycemia is an important indicator of diabetic status. The aim of this research was to evaluate the effect of Annona muricata L. extract on the in vitro intestinal glucose absorption in diabetic rats and in vivo antihyperglycemic activity in both normal and diabetic rats. Methods: Phytochemical screening of the aqueous extract from the leaves of A. muricata was carried out. Albino rats were randomly assigned into normal and diabetic groups. Each group was divided into three subgroups: control (vehicle), experimental (A. muricata), and standard (Metformin) groups, to determine antihyperglycemic activity at different times after glucose overload. The everted intestinal sac technique was used to study intestinal glucose absorption in diabetic rats. Results: Aqueous leaf extract of Peruvian A. muricata exhibited statistically significant (P &lt; 0.05) in vivo antihyperglycemic activity in both normal and diabetic rats when compared to the control group. The magnitude of the effect was similar to metformin treatment. Moreover, the aqueous leaf extract of A. muricata significantly diminished in vitro intestinal glucose absorption, with a magnitude similar to metformin treatment. Phytochemical analysis of the aqueous extract revealed the presence of tannins, flavonoids, alkaloids, and leucoanthocyanidins, among others. Conclusion: This study reveals that A. muricata aqueous extract is able to reduce in vitro intestinal glucose absorption and improve oral glucose tolerance in rats.

Gliquidone ameliorates hepatic insulin resistance in streptozotocin-induced diabetic Sur1−/− rats

Gliquidone was suggested to exert hypoglycemic effect through enhancing hepatic insulin sensitivity. However, inadequate in vivo evidences make this statement controversial. The aim of the present study was to clarify the insulin-sensitizer role of gliquidone in liver and muscle, so as to confirm its extra-pancreatic effects in vivo. TALEN technique was used to create Sur1 knockout (Sur1−/−) rats. Diabetic Sur1−/− rat models were established by high-fat diet combined with streptozotocin, and which were randomly divided into three groups: gliquidone, metformin and saline, treated for 8 weeks. Fasting blood glucose (FBG) and body mass were tested each week. IPGTT, IPITT and hyperinsulinemic-euglycemic clamp tests were used to evaluate glucose tolerance and insulin sensitivity, respectively. Key mediators of glucose metabolism in liver and skeletal muscle and the activity of AKT and AMPK in these tissues were further analyzed. We found that gliquidone decreased FBG and increased insulin sensitivity without increasing insulin secretion in diabetic Sur1−/− rats. Further exploration implied that gliquidone mainly increased hepatic glycogen storage and decreased gluconeogenesis, which were accompanied with activation of AKT, but not enhanced muscle GLUT4 expression. However, both these effects were still weaker than that of metformin. These results suggested that gliquidone could exerts an extra-pancreatic hypoglycemic effect by improving insulin sensitivity, which might be largely attributes to its additional insulin sensitizer role in hepatic glucose metabolism.

Bitter melon fruit extract enhances intracellular ATP production and insulin secretion from rat pancreatic β-cells.

Bitter melon (Momordica charantia L.) has been shown to have various health-promoting activities, including antidiabetic and hypoglycaemic effects. Improvement in insulin sensitivity and increase in glucose utilisation in peripheral tissues have been reported, but the effect on insulin secretion from pancreatic β-cells remains unclear. In this study, we investigated the effect of bitter melon fruit on insulin secretion from β-cells and the underlying mechanism. The green fruit of bitter melon was freeze-dried and extracted with methanol. The bitter melon fruit extract (BMFE) was fractionated using ethyl acetate (fraction A), n-butanol (fraction B) and water (fraction C). Insulin secretory capacity from INS-1 rat insulinoma cell line and rat pancreatic islets, as well as glucose tolerance in rats by oral glucose tolerance test (OGTT), was measured using BMFE and fractions. ATP production in β-cells was also examined. BMFE augmented insulin secretion from INS-1 cells in a dose-dependent manner. The significant augmentation of insulin secretion was independent of the glucose dose. Fraction A (i.e. hydrophobic fraction), but not fractions B and C, augmented insulin secretion significantly at the same level as that by BMFE. This finding was also observed in pancreatic islets. In OGTT, BMFE and fraction A decreased blood glucose levels and increased serum insulin levels after glucose loading. The decrease in blood glucose levels was also observed in streptozotocin-induced diabetic rats. In addition, BMFE and fraction A increased the ATP content in β-cells. We concluded that hydrophobic components of BMFE increase ATP production and augment insulin secretion from β-cells, consequently decreasing blood glucose levels.