Impaired Glucose Tolerance In Rats Research Articles

Metformin Influence on the Intestinal Microbiota and Organism of Rats with Metabolic Syndrome.

Metformin is a first-line drug for DM2 treatment and prevention, but its complex effect on impaired glucose tolerance (IGT), including its influence on myocardial resistance to ischemia-reperfusion injury, is not completely studied. We aimed to evaluate the influence of metformin on the intestinal microbiota (IM), metabolism, and functional and morphological characteristics of myocardium in rats with IGT. IGT was modelled in SPF Wistar rats with a high-fat diet and streptozotocin and nicotinamide injection. Rats were divided into three groups: IGT (without treatment), IGT MET (metformin therapy), and CRL (without IGT induction and treatment). IGT group was characterized by: higher body weight, increased serum glucose and total cholesterol levels, atherogenic coefficient, impairment in the functional parameters of the isolated heart during perfusion, and larger myocardium infarction (MI) size in comparison with the CRL group. IM of IGT rats differed from that of CRL: an increase of Bacteroides, Acinetobacter, Akkermansia, Roseburia, and a decrease of Lactobacillus genera representation. Metformin therapy led to the diminishing of metabolic syndrome (MS) symptoms, which correlated with IM restoration, especially with the growth of Akkermansia spp. and decline of Roseburia populations and their influence on other members of IM. The obtained results allow us to consider from a new point of view the expediency of probiotic A. muciniphila use for MS treatment.

Effect of Type 2 Diabetes and Impaired Glucose Tolerance on Digestive Enzymes and Glucose Absorption in the Small Intestine of Young Rats.

The reactions of intestinal functional parameters to type 2 diabetes at a young age remain unclear. The study aimed to assess changes in the activity of intestinal enzymes, glucose absorption, transporter content (SGLT1, GLUT2) and intestinal structure in young Wistar rats with type 2 diabetes (T2D) and impaired glucose tolerance (IGT). To induce these conditions in the T2D (n = 4) and IGT (n = 6) rats, we used a high-fat diet and a low dose of streptozotocin. Rats fed a high-fat diet (HFD) (n = 6) or a standard diet (SCD) (n = 6) were used as controls. The results showed that in T2D rats, the ability of the small intestine to absorb glucose was higher in comparison to HFD rats (p < 0.05). This was accompanied by a tendency towards an increase in the number of enterocytes on the villi of the small intestine in the absence of changes in the content of SGLT1 and GLUT2 in the brush border membrane of the enterocytes. T2D rats also showed lower maltase and alkaline phosphatase (AP) activity in the jejunal mucosa compared to the IGT rats (p < 0.05) and lower AP activity in the colon contents compared to the HFD (p < 0.05) and IGT (p < 0.05) rats. Thus, this study provides insights into the adaptation of the functional and structural parameters of the small intestine in the development of type 2 diabetes and impaired glucose tolerance in young representatives.

Identifying potential therapeutic targets of Tang-Yi-Ping for the treatment of impaired glucose tolerance: a tandem mass tag-labeled quantitative proteomic analysis.

BackgroundThis study uses the tandem mass tag (TMT)-labeled quantitative proteomic analysis to identify potential therapeutic protein targets of a Chinese prescription called Tang-Yi-Ping (TYP) for the treatment of impaired glucose tolerance (IGT) in rats.MethodsA total of 31 specific-pathogen free (SPF) male Wistar rats were used in our study. Ten were randomly selected as a control group, while 21 received a high-sugar and high-fat diet combined with an intraperitoneal injection of streptozotocin to establish IGT subjects. After eliminating 2 rats without successful modeling, 19 were randomly divided into a TYP group (n=9) and IGT model group (n=10). The TYP group was given a TYP decoction of 6.36 mg/kg−1/d−1. After 8 weeks of intervention, blood glucose-related indicators were measured, and cell morphology was observed by hematoxylin and eosin (HE) staining. TMT-labeled proteomic analysis was applied to detect the differentially expressed proteins (DEPs) in the pancreases of the three groups. The intersection of the DEPs in both the TYP group and IGT model group underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify the related biological functions and signal transduction pathways. Finally, western blot (WB) was used to verify the TMT proteomics results.ResultsTYP can effectively reduce blood glucose and improve islet morphology in IGT rats. We identified a total of 16 potential therapeutic protein targets of TYP, 4 of which were upregulated, while 12 were downregulated, including Rbp4, Fam3b, Flot2, etc. [fold change (FC) >1.1, P<0.05]. The significant signal transduction pathways included arginine and proline metabolism, glyceride metabolism, glycerophospholipid metabolism, mTOR, Wnt, and insulin signaling pathways.ConclusionsFor anti-IGT therapy, we found TYP regulates 16 protein targets, multiple biological functions, and multiple signal transduction pathways. This study thus makes a significant contribution to identifying new potential therapeutic targets for treating IGT.

Berberine Slows the Progression of Prediabetes to Diabetes in Zucker Diabetic Fatty Rats by Enhancing Intestinal Secretion of Glucagon-Like Peptide-2 and Improving the Gut Microbiota.

BackgroundBerberine is a plant alkaloid that has multiple beneficial effects against intestine inflammation. In our previous study, we have found that berberine also possesses an antidiabetic effect. However, whether berberine is useful in the prevention of type 2 diabetes mellitus (T2DM) through its effect on intestine endocrine function and gut microbiota is unclear.AimTo investigate the effects of berberine in the prevention of T2DM, as well as its effects on intestine GLP-2 secretion and gut microbiota in ZDF rats.MethodsTwenty Zucker Diabetic Fatty (ZDF) rats were fed a high-energy diet until they exhibited impaired glucose tolerance (IGT). The rats were then divided into two groups to receive berberine (100 mg/kg/d; berberine group) or vehicle (IGT group) by gavage for 3 weeks. Five Zucker Lean (ZL) rats were used as controls. Fasting blood glucose (FBG) was measured, an oral glucose tolerance test was performed, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated. Intestinal expression of TLR-4, NF-κB, TNF-α, mucin, zona occludens-1 (ZO-1) and occludin were assessed (immunohistochemistry). Plasma levels and glutamine-induced intestinal secretion of glucagon-like peptide-1 (GLP-1) and GLP-2 were measured (enzyme-linked immunosorbent assay). The plasma lipopolysaccharide (LPS) level was measured. Fecal DNA extraction, pyrosequencing, and bioinformatics analysis were performed.ResultsAfter 3 weeks of intervention, diabetes developed in all rats in the IGT group, but only 30% of rats in the berberine group. Treatment with berberine was associated with reductions in food intake, FBG level, insulin resistance, and plasma LPS level, as well as increases in fasting plasma GLP-2 level and glutamine-induced intestinal GLP-2 secretion. Berberine could increase the goblet cell number and villi length, and also reverse the suppressed expressions of mucin, occludin, ZO-1 and the upregulated expressions of TLR-4, NF-κB and TNF-α induced in IGT rats (P<0.05). Berberine also improved the structure of the gut microbiota and restored species diversity.ConclusionBerberine may slow the progression of prediabetes to T2DM in ZDF rats by improving GLP-2 secretion, intestinal permeability, and the structure of the gut microbiota.

Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance

Impaired glucose tolerance (IGT) increases cardiovascular risk and can enlarge myocardial infarction (MI) incidence and severity. There is lack of information about cardioprotective potential of glucose-lowering drugs in IGT. We aimed to evaluate the sustainability of myocardium to ischemia–reperfusion injury in diabetic and IGT rats and to study cardioprotective action of metformin and liraglutide. Type 2 diabetes mellitus (DM) and IGT were modelled in Wistar rats by high-fat diet and streptozotocin + nicotinamide. 4 weeks after rats were divided into 4 groups: DM (without treatment) (n = 4), IGT (without treatment) (n = 4), IGT + MET (metformin 200 mg/kg per os once daily 8 weeks) (n = 4), IGT + LIRA (liraglutide 0.06 mg/kg s.c. once daily for 8 weeks) (n = 4). Control (n = 6) and high-fat diet (n = 8) groups were made for comparison. After 8 weeks ischemia–reperfusion injury in isolated hearts was performed. Hemodynamic parameters were evaluated and MI size was measured by staining of myocardium slices in triphenyltetrazolium chloride solution. Blood glucose level was measured during the study. Both IGT and DM led to similar worsening of hemodynamic parameters during ischemia–reperfusion period, in comparison with control group. MI size in IGT (56.76 (51.58; 69.07) %) and DM (57.26 (45.51; 70.08) %) groups was significantly larger than that in control group (42.98 (33.26; 61.84) %) and did not differ between each other. MI size in high-fat diet group (56.98 (47.11; 62.83) %) was as large as in IGT and DM groups (p > 0.05). MI size in IGT + MET (42.11 (38.08; 71.96) %) and IGT + LIRA (42.50 (31.37; 60.40) %) was smaller than in both DM and IGT groups (p < 0.05 for multiple comparison). Myocardium damage size did not differ in IGT + MET and IGT + LIRA groups (p > 0.05). Only LIRA, but not MET administration to IGT rats led to ischemic contracture reduction. Glycemic control was similarly satisfactory in IGT, IGT + MET, IGT + LIRA groups. Thus, IGT and DM have similarly pronounced negative influence on hemodynamics and MI size in rat transient global ischemia ex vivo. Obesity development also has negative impact on the MI size. Both MET and LIRA have infarct-limiting effect independent on their influence on glucose level. LIRA, but not MET, diminishes ischemic contracture in IGT rats.

Effect of transcutaneous auricular vagus nerve stimulation on hyperglycemia and insulin receptors expression in impaired glucose tolerance rats

To explore the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on blood glucose regulation and the expression of insulin receptors (INR) of hypothalamus, liver and skeletal muscle tissues in impaired glucose tolerance (IGT) rats, so as to reveal its mechanisms underlying improvement of IGT. Thirty-six male Wistar rats were randomly divided into control, model, transcutaneous auricular none-vagus nerve stimulation (tnVNS), and taVNS groups (n=9 in each group). The IGT model was established by feeding the rats with high-fat and high-sugar diet for 5 weeks, and subsequent intraperitoneal injection of a dose of streptozotocin (20 mg/kg). Transcutaneous electrostimulation (2 mA, 2 Hz/15 Hz) was applied to auricular concha (taVNS) or auricular margin (tnVNS), respectively. The treatment was conducted for 30 min once daily for 4 weeks. The body weight, fasting plasma glucose (FPG), 2 h plasma glucose (2 h PG) were recorded every week. The contents of plasma insulin (INS), glucagon (GC), glycosylated hemoglobin (GHbA1c) were detected by using enzyme linked immunosorbent assay (ELISA). The expression levels of INR in hypothalamus, liver and skeletal muscle tissues were detected by Western blot. After modeling, the rats' body weight, the contents of FPG, 2 h PG, GC and GHbA1c were significantly up-regulated (P<0.001, P<0.05, P<0.01), and the content of INS and expression of INR in hypothalamus, liver and skeletal muscle tissues were significantly down-regulated in the model group compared with the control group (P<0.001, P<0.01, P<0.05). Following the treatment, the increased FPG, 2 h PG, GC, and the decreased INS and INR expression of hypothalamus, liver and skeletal muscle tissues were apparently reversed in the taVNS group relevant to the model group (P<0.001, P<0.01, P<0.05). Compared with the tnVNS group, the FPG and 2 h PG contents were considerable decreased, and the content of INS and INR expression of hypothalamus and liver were obviously increased in the taVNS group (P<0.001, P<0.05, P<0.01). taVNS can improve the blood glucose and insulin sensitivity in IGT rats, which may contribute to its effectiveness in up-regulating the expression of INR in hypothalamus, liver and skeletal muscle tissues.

Cinnamon Attenuated Long-Term IGT-Induced Retinal Abnormalities via Regulation of Glucose Homeostasis in Neonatal Streptozotocin Induced Rat Model.

Diabetic retinopathy (DR) is one of the major causes of blindness all over the world. According to the previous studies, impaired glucose tolerance (IGT) has been linked to retinal dysfunction/vascular damage. Decreased retinal function is an initial event of early DR. Although the biochemical and molecular events are not fully understood, glial activation, angiogenesis and oxidative stress are some of the pathways associated with early retinal abnormalities. Since IGT is associated with development of retinal dysfunction/vascular damage; as a preventive strategy, we have studied beneficial effect of Cinnamon as a hypoglycaemic agent on long-term IGT induced retinal abnormalities using neonatal streptozotocin (nSTZ) rat model. Control, IGT rats were maintained on AIN-93M diet alone and another set of IGT rats were maintained on AIN-93M diet with 3% Cinnamon for 8months. At the end of the study, untreated IGT rats developed retinal functional abnormalities as assessed by electroretinogram (ERG) and the retinal structure did not alter as assessed by H&E staining. Further, increase in expressions of GFAP, VEGF and decreased expression of rhodopsin in untreated IGT rat retinas. 4-HNE, a marker of oxidative stress was also elevated in IGT state. Supplementation of Cinnamon to IGT rats had lowered fasting and postprandial glucose levels and also prevented retinal functional abnormalities. Further, Cinnamon protected photoreceptor cell damage, suppressed glial activation, angiogenesis and oxidative stress as there was an improved rhodopsin expression, inhibited elevated expressions of GFAP, VEGF and 4-HNE respectively. In conclusion, Cinnamon attenuated IGT induced retinal abnormalities probably through its hypoglycemic property.

Effects of Light-at-Night on the Rat Liver – A Role for the Autonomic Nervous System

Exposure to light at night (LAN) has been associated with serious pathologies, including obesity, diabetes and cancer. Recently we showed that 2 h of LAN impaired glucose tolerance in rats. Several studies have suggested that the autonomic nervous system (ANS) plays an important role in communicating these acute effects of LAN to the periphery. Here, we investigated the acute effects of LAN on the liver transcriptome of male Wistar rats. Expression levels of individual genes were not markedly affected by LAN, nevertheless pathway analysis revealed clustered changes in a number of endocrine pathways. Subsequently, we used selective hepatic denervations [sympathetic (Sx), parasympathetic (Px), total (Tx, i.e., Sx plus Px), sham] to investigate the involvement of the ANS in the effects observed. Surgical removal of the sympathetic or parasympathetic hepatic branches of the ANS resulted in many, but small changes in the liver transcriptome, including a pathway involved with circadian clock regulation, but it clearly separated the four denervation groups. On the other hand, analysis of the liver metabolome was not able to separate the denervation groups, and only 6 out of 78 metabolites were significantly up- or downregulated after denervations. Finally, removal of the sympathetic and parasympathetic hepatic nerves combined with LAN exposure clearly modulated the effects of LAN on the liver transcriptome, but left most endocrine pathways unaffected.Conclusion: One-hour light-at-night acutely affects the liver transcriptome. Part of this effect is mediated via the nervous innervation, as a hepatectomy modulated and reduced the effect of LAN on liver transcripts.

Interesterified soybean oil promotes weight gain, impaired glucose tolerance and increased liver cellular stress markers

Interesterified fats have largely replaced hydrogenated vegetable fat, which is rich in trans fatty acids, in the food industry as an economically viable alternative, generating interest to study their health effects. The aim of this study was to evaluate the effect that interesterification of oils and fat has on lipid-induced metabolic dysfunction, hepatic inflammation and ER stress. Five week-old male Wistar rats were randomly divided into three experimental groups, submitted to either normocaloric and normolipidic diet containing 10% of lipids from unmodified soybean oil (SO) or from interesterified soybean oil (ISO), and one more group submitted to a high fat diet (HFD) containing 60% of fat from lard as a positive control, for 8 or 16 weeks. Metabolic parameters and hepatic gene expression were evaluated. The HFD consumption led to increased body mass, adiposity and impaired glucose tolerance compared to SO and ISO at both time points of diet. However, the ISO group showed an increased body mass gain, retroperitoneal WAT mass, fasting glucose, and impaired glucose tolerance during ipGTT at 16 weeks compared to SO. Moreover, at 8 weeks, hepatic gene expression of Atf3 and Tnf were increased in the ISO group compared to the SO group. Thus, replacement of natural fat with interesterified fat on a normocaloric and normolipidic diet negatively modulated metabolic parameters and resulted in impaired glucose tolerance in rats.

Improvement of oral contraceptive-induced glucose dysregulation and dyslipidemia by valproic acid is independent of circulating corticosterone

Context: Cardiometabolic disorders are rapidly becoming major public health challenges. Valproic acid (VPA) is a widely prescribed anticonvulsant drug. Objective: We hypothesized that treatment with VPA would improve the regulation of glucose and atherogenic dyslipidemia through reduction in circulating corticosterone. Methods: Female Wistar rats recieved (p.o.) combined oral contraceptive (COC) containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and valproic acid (VPA; 20 mg) for 8 weeks. Results: Treatment with COC led to elevated fasting blood glucose, insulin, corticosterone, triglycerides (TG), TG/HDL-cholesterol ratio, insulin resistance (IR) and impaired glucose tolerance. VPA significantly attenuated the alterations induced by COC treatment, but did not affect the corticosterone level. However, VPA treatment led to significant increases in plasma insulin, corticosterone, atherogenic lipids and impaired glucose tolerance in rats not treated with COC. Conclusion: The findings in this study suggest that VPA mitigates against the development of COC-induced insulin resistance and dyslipidemia independent of elevated circulating corticosterone.

Knockdown of neuropeptide Y in the dorsomedial hypothalamus reverses high-fat diet-induced obesity and impaired glucose tolerance in rats.

Neuropeptide Y (NPY) in the dorsomedial hypothalamus (DMH) plays an important role in the regulation of energy balance. While DMH NPY overexpression causes hyperphagia and obesity in rats, knockdown of NPY in the DMH via adeno-associated virus (AAV)-mediated RNAi (AAVshNPY) ameliorates these alterations. Whether this knockdown has a therapeutic effect on obesity and glycemic disorder has yet to be determined. The present study sought to test this potential using a rat model of high-fat diet (HFD)-induced obesity and insulin resistance, mimicking human obesity with impaired glucose homeostasis. Rats had ad libitum access to rodent regular chow (RC) or HFD. Six weeks later, an oral glucose tolerance test (OGTT) was performed for verifying HFD-induced glucose intolerance. After verification, obese rats received bilateral DMH injections of AAVshNPY or the control vector AAVshCTL, and OGTT and insulin tolerance test (ITT) were performed at 16 and 18 wk after viral injection (23 and 25 wk on HFD), respectively. Rats were killed at 26 wk on HFD. We found that AAVshCTL rats on HFD remained hyperphagic, obese, glucose intolerant, and insulin resistant relative to lean control RC-fed rats receiving DMH injection of AAVshCTL, whereas these alterations were reversed in NPY knockdown rats fed a HFD. NPY knockdown rats exhibited normal food intake, body weight, glucose tolerance, and insulin sensitivity, as seen in lean control rats. Together, these results demonstrate a therapeutic action of DMH NPY knockdown against obesity and impaired glucose homeostasis in rats, providing a potential target for the treatment of obesity and diabetes.

Fasting for 3 days during the suckling-weaning transient period in male rats induces metabolic abnormalities in the liver and is associated with impaired glucose tolerance in adulthood.

Recent studies suggest that nutritional status during developmental periods is associated with subsequent development of metabolic abnormalities. In this study, we examined whether malnutrition by fasting for 3 days during the suckling-weaning transient period induces subsequent development of metabolic abnormalities in rats. Male Sprague-Dawley rats were fasted for 3 days during the suckling-weaning transient period. They are subsequently fed a high-fat, high-sucrose (HF) or low-fat, high-starch (LF) diet for 14 weeks from 17 weeks of age, and the liver and blood samples were collected for measuring mRNA and protein levels of metabolic genes and blood concentrations of glucose and insulin, respectively. Fasting for 3 days during the suckling-weaning transient period induced impaired glucose tolerance in rats fed the LF diet in adulthood. Liver triglycerides in rats fed the HF diet in adulthood increased to 140 % in rats fasted for 3 days during the suckling-weaning transient period compared with those non-fasted. Furthermore, liver expression of FBP1 and ACCα genes in adult rats fed the LF diet increased to 125 and 145 %, respectively, in rats fasted for 3 days during the suckling-weaning transient period compared to non-fasted rats. PEPCK1 protein expression levels in rats fed the LF diet were higher in rats fasted for 3 days during the suckling-weaning transient period than in non-fasted rats. Fasting for 3 days in rats during the suckling-weaning transient period enhances metabolic abnormalities in animals fed a HF or LF diet in adulthood by confounding metabolism of lipid and sugar in the liver.

Adipose tissue hypoxia and low-grade inflammation: a possible mechanism for ethanol-related glucose intolerance?

The exact mechanism of ethanol's effects on glucose tolerance has not been well determined. The present study focuses for the first time on hypoxia and low-grade inflammation in adipose tissue (AT). In the in vivo experiments, twenty-four male Wistar rats were randomly allocated into control and ethanol feeding groups. Ethanol-treated rats received edible ethanol once a day at a total dosage of 5 g/kg per d, and the controls received distilled water. Ethanol volumes were adjusted every week. At the end of 8 weeks, we carried out an oral glucose tolerance test. Blood and AT were collected for measuring hypoxia-inducible factor-1α (HIF-1α), GLUT1, TNF-α, IL-6, leptin and vascular endothelial growth factor (VEGF). In the in vitro experiments, differentiated OP9 adipocytes were incubated with 100 mm of ethanol for 48 h; the media and cells were then collected for measuring HIF-1α, GLUT1, TNF-α and IL-6. The results showed that long-term ethanol consumption impaired glucose tolerance in rats. Ethanol consumption had little influence on body weight, but both epididymal and perirenal AT were markedly enlarged in the ethanol-treated rats as compared to the controls. Visceral adipose tissue (VAT) had accumulated, and the protein levels of HIF-1α and GLUT1, the indicators of hypoxia in rat epididymal AT and OP9 adipocytes, were elevated. Secondary to the AT hypoxia, the levels of inflammation-related adipokines, such as TNF-α, IL-6, leptin and VEGF, were increased. Based on these findings, we conclude that VAT hypoxia and low-grade inflammation might be a new mechanism in the treatment of ethanol-related diabetes.

Influence of Dihydromyricetin on Lowering Blood Glucose Concentration and Reducing Early Kidney Damage in Imparied Glucose Tolerance Rats

Diabetic nephropathy (DN) is a common complication of diabetes and it is related to irreversible kidney damages and chronic renal failure. Impaired glucose tolerance (IGT) is an early stage in the development of diabetes and DN. Early detection of IGT and treatment of its associated early kidney damage can effectively prevent the development of DN. In this paper, the influence of dihydromyricetin (DHM) on lowering blood glucose concentration and reducing early kidney damage in IGT rats was studied. Animal model of IGT rats was built by two week intragastric injection of D-galactose and treated with eight weeks of intragastric injection of DHM at two dose levels. The concentrations of fasting blood glucose (FBG), two-hour postprandial blood glucose (2hBG), insulin levels, contents of microalbuminuia (mAlb) and blood urea nitrogen (BUN), and activities of lactate dehydrogenase (LDH) in kidney were analysed and compared with those in control groups. Experimental results indicated that DHM treatment can significantly lower the levels of two-hour postprandial blood glucose and insulin, decrease the content of mAlb and the activities of LDH in kidney, but does not influence the level of BUN. The study suggested that DHM can effectively improve the states of IGT rats and provide a protective effect against early kidney damage.

The Fruiting Bodies, Submerged Culture Biomass, and Acidic Polysaccharide Glucuronoxylomannan of Yellow Brain Mushroom Tremella mesenterica Modulate the Immunity of Peripheral Blood Leukocytes and Splenocytes in Rats with Impaired Glucose Tolerance

The prevalence of diabetes mellitus (DM), a chronic disease with hyperglycemia and impaired immune function, is increasing worldwide. Progression from impaired glucose tolerance (IGT) to type 2 DM has recently become a target for early intervention. The fruiting bodies (FB) and submerged culture mycelium (CM) of Tremella mesenterica, an edible and medicinal mushroom, have been demonstrated to have antihyperglycemic and immunomodulatory activities in type 1 DM rats. Herein, we investigated the effects of acidic polysaccharide glucuronoxylomannan (GX) extracted from CM on the immunocyte responses. Male Wistar rats were injected with streptozotocin (65 mg/kg) plus nicotinamide (200 mg/kg) for the induction of IGT, and gavaged daily with vehicle, FB, CM, or GX (1 g/kg/day). Rats injected with saline and gavaged vehicle were used as controls. Two weeks later, peripheral blood leukocytes (PBLs) and splenocytes were collected. Ingestion of FB, CM, and GX significantly decreased blood glucose levels in the postprandial period and in oral glucose tolerance test, and partially reversed T-splenocytic proliferation in IGT rats. CM significantly decreased T-helper lymphocytes in the PBLs and B-splenocytes. In addition, FB, CM, and GX significantly reversed the IGT-induced decreases in tumor necrosis factor-α production; GX significantly increased interleukin-6 production in T-lymphocytes in the PBLs and splenocytes; and CM and GX significantly reversed IGT-induced decrease in interferon-γ production in T-lymphocytes in the spleen. In conclusion, FB, CM, and acidic polysaccharide GX of T. mesenterica may increase T-cell immunity via the elevation of proinflammatory and T-helper cytokine production in rats with impaired glucose tolerance.

Probiotic Lactobacillus casei Zhang ameliorates high-fructose-induced impaired glucose tolerance in hyperinsulinemia rats

To evaluate the preventive and therapeutic effects of Lactobacilluscasei Zhang on impaired glucose tolerance (IGT) by using fructose-induced hyperinsulinemia rats. Rats were fed 25 % fructose solution for hyperinsulinemia with L.casei Zhang for prevention or therapy. Serum levels of insulin, glucagon-like peptide-2 (GLP-2), osteocalcin, malondialdehyde (MDA), total intestinal bile acids and hepatic glycogen contents were determined by assay kits. The major bacteria from feces and liver expression of adiponectin receptor 2 (AdipoR2), liver X receptor-α (LXR-α), peroxisome proliferator-activated receptor gamma (PPAR-γ) and vitamin K epoxide reductase complex subunit 1 mRNA were assessed by RT-PCR. Pancreas injury was evaluated by histological analysis. Lactobacilluscasei Zhang significantly increased numbers of Lactobacillus and Bifidobacterium and decreased Clostridium in the intestine (p < 0.01). Meanwhile, liver glycogen contents were significantly decreased (p < 0.05). In preventive group, accompanied by significantly lower insulin and GLP-2 levels (p < 0.05), L.casei Zhang prevented rats from an increase in oral glucose tolerance area under curve (AUC) which was significant in hyperinsulinemia group (p < 0.05). In therapeutic group, L.casei Zhang administration possessed improved glucose tolerance (p < 0.05), which were associated with increased osteocalcin level (p < 0.01), improved intestinal bile acids secretion (p = 0.060), decreased serum MDA levels (p < 0.05) and upregulation of LXR-α, PPAR-γ and AdipoR2 gene expression, as well as an increase in Bacteroides fragilis (p < 0.05). Lactobacilluscasei Zhang administration exert both preventive and ameliorative effect on oral glucose tolerance AUC in IGT rats but may be via different mechanisms. L.casei Zhang could prevent rats from increased AUC through GLP-2 lowering, while the ameliorative effect in high-fructose-fed post-adolescent rats may be via B. fragilis enriched vitamin K2-dependent osteocalcin mechanism in which AdipoR2, LXR-α and PPAR-γ signaling were involved.

Assessment of Bridelia ferruginea benth for its therapeutic potential in pregnancy-induced impaired glucose tolerance in rats

Background : Pregnancy induced diabetes also known as gestational diabetes develops during pregnancy. Pregnancy is an insulin resistant state that may induce impaired glucose tolerance and often gestational diabetes in susceptible women. Gestational diabetes causes serious problems to the mother and the baby. Therefore, the use of herbal remedies such as Bridelia ferruginea with the potential ability to improve glucose tolerance during pregnancy will definitely improve pregnancy outcome in gestational diabetes. Aim : This paper presents an evaluation of possible therapeutic potential of B. ferruginea in gestational diabetes by assessing the anti-glycaemic effects of the plant’s aqueous extracts on pregnancy-induced glucose intolerance in rats. Materials and Methods : Adult virgin, timed-pregnant and non-pregnant rats were subjected to brief ether anaesthesia after 18-hour overnight fasting period to allow for oro-gastric administration of glucose load at 3.0g/kg body weight as 30% solution. The oral glucose load was given at an administration volume of 1.0ml/100g bw. Results : Oral glucose tolerance test showed that pregnancy induced glucose intolerance in the rats. However, B. ferruginea caused a reduction in glycaemic response to glucose challenge and an increased glucose tolerance in rats that had pregnancy-induced glucose intolerance. Thus, diabetogenic effect of pregnancy was ameliorated by oral administration of aqueous extracts of B. ferruginea to pregnant albino rats. Keywords : Gestational diabetes, pregnancy-induced diabetes, hypoglycaemic, glycaemic response, glucose tolerance.

Clofibrate‐Induced Reduction of Plasma Branched‐Chain Amino Acid Concentrations Impairs Glucose Tolerance in Rats

It has been reported that branched-chain amino acid (BCAA) administration stimulates glucose uptake into muscles and whole body glucose oxidation in rats. The authors examined the effect of decreased plasma BCAA concentrations induced by clofibrate treatment on glucose tolerance in rats. Since clofibrate, a drug for hyperlipidemia (high serum triglyceride concentration), is a potent inhibitor of the branched-chain α-keto acid dehydrogenase kinase, clofibrate treatment (0.2 g/kg body weight) activated the hepatic branched-chain α-keto acid dehydrogenase complex, resulting in decreased plasma BCAA concentrations by 30% to 50% from the normal level. An intraperitoneal glucose tolerance test was conducted after clofibrate administration, and the results showed that peak plasma glucose concentration and the area under the curve of glucose concentration during the intraperitoneal glucose tolerance test were significantly higher in clofibrate-treated rats than in control rats. This impaired glucose tolerance in the clofibrate-treated rats was ameliorated by administration of BCAAs (0.45 g/kg body weight, leucine:isoleucine:valine = 2:1:1), which kept plasma BCAA concentrations at normal levels during the intraperitoneal glucose tolerance test. These results suggest that plasma BCAAs play an important role in maintaining normal glucose tolerance in rats.

The combination of Pitavastain and ischemic postconditioning attenuates myocardial ischemic/reperfusion injury in impaired glucose tolerance rat in vivo

Background and ObjectivesMyocardial ischemia-reperfusion injury (MIRI) can be alleviated by ischemia post-conditioning (IPC) and/or statin post-conditioning (SPC), and their combination. However, it is unclear how the cardio-protection works in impaired...

Berberine reduces insulin resistance induced by dexamethasone in theca cells in vitro

Theca cells with dexamethasone-induced insulin resistance showed defective glucose uptake and excessive testosterone production, both of which were effectively antagonized by berberine. Therefore, insulin-resistant theca cells may contribute to the pathogenesis of hyperandrogenism in polycystic ovary syndrome.