Increased Serum Insulin Research Articles

Comparative Effects of Extracts from Black Rice or Pathum Rice Combined with Cereals on Blood Glucose Levels, Serum Insulin Levels and Blood Chemistry in Diabetic Rats

Rice is one of the major cereal crops in several Asian countries. It contains a variety of nutrients and provides valuable health benefits. The antidiabetic activity of rice combined with cereals has not been studied. Therefore, the present study was carried out to determine and compare the effects of extracts from Black rice (BRE), Pathum rice (PTRE), Black rice combined with cereals (BRCE), and Pathum rice combined with cereals (PTRCE) on body weight, blood glucose levels, serum insulin levels and blood chemistry of Streptozotocin (STZ)-induced diabetic rats. The results revealed that BRCE exhibited the highest activity in reducing fasting blood glucose (FBG) levels and increasing serum insulin levels, and also recovered the lipid profiles, renal function and hepatic function resulting from STZ in the diabetic rats, followed by BRE, PTRCE and PTRE, respectively. Also, BRCE exhibited an activity with similar potential to Glibenclamide. The findings indicate that the rice extracts possess antidiabetic activity which exerts the activity by increasing serum insulin resulting in reduction of blood glucose. Rice combined with cereals provides better antidiabetic activity and could be a source of valuable antidiabetic materials. HIGHLIGHTS Extracts from Black rice and Pathum Thani fragrant rice exhibit antidiabetic activity in Streptozotocin-induced diabetic rats. Antidiabetic activity of the extracts from Black rice and Pathum Thani fragrant rice is due to an increase in insulin secretion. Black rice exhibits antidiabetic activity higher than Pathum Thani fragrant rice. Combination with cereals could enhance the antidiabetic activity of rice. The extracts from Black rice and Pathum Thani fragrant rice may be useful for the management of diabetes mellitus. GRAPHICAL ABSTRACT

Antihyperglycemic activity of a novel polyherbal formula (HF344), a mixture of fifteen herb extracts, for the management of type 2 diabetes: Evidence from in vitro, ex vivo, and in vivo studies

Antihyperglycemic effects of a novel polyherbal formula (HF344), comprising fifteen Thai herbal extracts, were elucidated for pharmacological mechanisms and potential for managing type 2 diabetes mellitus, by employing in vitro, ex vivo, and in vivo approaches. LC/MS analysis of HF344 extract revealed several phytoconstituents, with piperine identified as the major active compound. HF344 extract significantly enhanced insulin secretion in RINm5F cells in vitro and inhibited glucose uptake into the everted sacs of the mouse small intestine ex vivo in a concentration-dependent manner compared to the control (p < 0.05). It exhibited potent α-glucosidase inhibition in vitro, with an IC50 of 96.74 μg/mL. Moreover, HF344 extract upregulated mRNA levels of GLUT1 in L6 skeletal myoblasts, suggesting increased glucose uptake into skeletal muscle. In addition, in vivo antihyperglycemic effects were assessed in streptozotocin (STZ)-nicotinamide (NA)-induced diabetic mice. Acute oral toxicity testing confirmed the HF344 extract's safety, with an LD50 exceeding 2000 mg/kg. Oral administration of HF344 extract (500 and 1000 mg/kg) in STZ-NA-induced diabetic mice significantly reduced the area under the fasting blood glucose (FBG)-time curve (AUC) in the oral glucose tolerance test (OGTT) model and treatment for 28-day reduced the FBG levels as compared with control (p < 0.05). This was accompanied by increased serum insulin levels and improved insulin resistance. HF344 extract also demonstrated a concentration-dependent inhibitory effect on malondialdehyde (MDA) production in vitro, with an IC50 of 7.24 μg/mL. Oral treatment with HF344 extract decreased MDA production in the homogenized muscle ex vivo collected from STZ-NA-induced mice. Furthermore, pretreatment with HF344 extract effectively restored the survival of RINm5F cells from STZ-induced damage. These findings suggest that HF344 is a promising polyherbal formula for managing blood glucose levels, enhancing insulin production, and providing antioxidant benefits in T2DM. Further research is required to evaluate the clinical efficacy and safety profiles of HF344.

Sustained linagliptin administration: superior glycemic control and less pancreatic injury in diabetic rats

While linagliptin is the most potent dipeptidyl peptidase 4 inhibitor, its use is limited due to poor bioavailability and the potential risk of pancreatic injury. Here, we investigated whether the sustained weekly administration of linagliptin could provide better effect compared to frequent daily oral administration. Type 2 diabetes was induced by feeding rats a high fructose/fat/salt diet followed by STZ injection. Compared to the partial glycemic control achieved with daily oral linagliptin, a weekly subcutaneous injection containing about one-fourth of the oral dose produced superior glycemic control, as evidenced by the 4-week postprandial glucose follow-up and oral glucose tolerance test. This was confirmed by the significant increase in serum insulin in the case of the sustained linagliptin administration. Higher levels of the anti-inflammatory cytokine adiponectin and lower triglyceride levels were observed after sustained linagliptin administration compared with daily oral linagliptin. In addition, sustained linagliptin displayed a significant increase in β-cells’ insulin immunoreactivity when compared with daily linagliptin. More reduction in collagen deposition and caspase-3 immunoreactivity in pancreatic tissue were observed in sustained linagliptin compared with oral linagliptin. In conclusion, sustained linagliptin administration provided superior glycemic control, which seems to be mediated by more reduction in pancreatic injury.

Ameliorative activity of standardized Coccoloba uvifera leaves extract against streptozotocin-induced diabetic rats via activation of IRS-1/PI3K/AKT/GLUT2 pathway in liver

BackgroundCoccoloba uvifera L. (Family: Polygonaceae) known as sea grape is natively distributed in middle and south America. The aqueous leaf extract showed inhibitory activities against α-glucosidase and α-amylase in previous reports. Moreover, the hydroalcoholic leaves extract ameliorated hyperglycemia in the oral glucose tolerance test. Despite these promising results, the extracts used in these studies were not standardized, nor was their mechanism of action elucidated. The current study aims to standardize the ethanolic C. uvifera leaves extract (CU) using markers, and assess its ameliorative activity against diabetes and its hepatoprotective activity against diabetic complications.ResultsStandardized leaves’ ethanolic extract contained 0.09 ± 0.00057 and 0.23 ± 0.0011 mg/g gallic acid and rutin, respectively, as estimated by HPLC. Administration of CU (100, 200 and 400 mg/kg) for 6 weeks ameliorated DM manifestations in STZ-induced diabetic rats in a dose-dependent manner. The ethanolic extract reduced fasting blood glucose, increased serum insulin and reduced elevated liver enzymes. CU counteracted oxidative stress, promoted glucose metabolizing enzymes and reduced gluconeogenesis enzymes. The underlying mechanism involved increased expression of IR, IRS-1, IRS-2 and GLUT2 in liver tissue through activation of PI3K/AKT signaling. The histopathological study demonstrated reduced inflammation and hepatocyte degeneration.ConclusionCU could be used as a promising antidiabetic drug with hepatoprotective activity in diabetes hepatic complications. The standardized CU ethanolic extract should be further assessed clinically alone or in combination with other antidiabetic remedies.

Low sucrose diets protect long-term memory and EPA & DHA enriched diets alter insulin resistance in a mouse model of chemotherapy

Chemotherapy-related cognitive impairment (CRCI) and affective symptoms negatively impact quality of life in breast cancer survivors. The aim of this study was to determine the efficacy of high eicosapentaenoic acid + docosahexaenoic acid (EPA+DHA) and low sucrose diets to alleviate these symptoms in a mouse model of chemotherapy. Potential mechanisms involving insulin resistance were explored. We hypothesized that diets enriched in EPA+DHA and low amounts of sucrose would protect against the impact of chemotherapy on measures of CRCI. Female C57Bl/6 mice were randomized to 1 of 4 diets (2% kcal eicosapentaenoic acid + docosahexaenoic acid [EPA+DHA]/high or low sucrose, low omega-3/high or low sucrose) for 6 weeks and treated with two injections of doxorubicin-based chemotherapy or vehicle during week 2 and 4. Behavioral tests were performed 7 days after second injection. Chemotherapy increased serum insulin and decreased body weight, locomotion and exploratory behavior (all p < .05). Low sucrose consumption resulted in better long-term memory regardless of chemotherapy or vehicle injection (p < .05). 2% EPA+DHA consumption lessened insulin resistance (p < .05); however, controlling for body weight attenuated this effect (p = .08). There were no significant differences by diet or injection on liver lipid content; however, liver lipid content was positively correlated with insulin resistance scores (p < .05). Low sucrose diets may protect long-term memory during chemotherapy. The effect of EPA+DHA on insulin resistance and affective side effects during chemotherapy requires further investigation.

Disruption of insulin receptor substrate 2 (IRS2) causes non-obese type 2 diabetes with β-cell dysfunction in the golden (Syrian) hamster

Because of the advent of genome-editing technology, gene knockout (KO) hamsters have become attractive research models for diverse diseases in humans. This study established a new KO model of diabetes by disrupting the insulin receptor substrate-2 (Irs2) gene in the golden (Syrian) hamster. Homozygous KO animals were born alive but with delayed postnatal growth until adulthood. They showed hyperglycemia, high HbA1c, and impaired glucose tolerance. However, they normally responded to insulin stimulation, unlike Irs2 KO mice, an obese type 2 diabetes (T2D) model. Consistent with this, Irs2 KO hamsters did not increase serum insulin levels upon glucose administration and showed β-cell hypoplasia in their pancreas. Thus, our Irs2 KO hamster provide a unique T2D animal model that is distinct from the obese T2D models. This model may contribute to a better understanding of the pathophysiology of human non-obese T2D with β-cell dysfunction, the most common type of T2D in East Asian countries, including Japan.

Biochemical study of the effect of lead exposure in nonobese gasoline station workers and risk of hyperglycemia: A retrospective case-control study.

Evaluate the relationship between blood lead (Pb) levels and other biomedical markers and the risk of diabetes in gasoline station workers. The participants were separated into 2 groups: group A consisted of 26 workers from gasoline filling stations, while group B comprised 26 healthy individuals. Serum levels of malondialdehyde, IL-1β, visfatin, insulin, fasting blood sugar, and vitamin D were assessed. Mean Pb level was significantly higher in group A compared to group B (almost 2.9 times higher levels) (14.43 ± 1.01 vs 5.01 ± 1.41, µg/dL). The levels of visfatin (23.19 ± 0.96 vs 3.88 ± 0.58, ng/mL), insulin (22.14 ± 1.31 vs 11.26 ± 0.75, mU/L), fasting blood sugar (118.4 ± 26.1 vs 82.7 ± 9.2, gm/dL), malondialdehyde (6.40 ± 0.27 vs 1.62 ± 0.21, nmol/mL), and IL-1β (330.25 ± 10.34 vs 12.35 ± 1.43, pg/mL) were significantly higher in group A, meanwhile; vitamin D (11.99 ± 1.55 vs 35.41 ± 3.16, ng/mL) were significantly lower in group A. A positive association exists between blood Pb levels and increased inflammatory markers. Lead exposure increases serum insulin and fasting blood sugar, which suggests that it is diabetogenic and that increased inflammation is a possible cause.

Anti-depressant effect of Naringenin-loaded hybridized nanoparticles in diabetic rats via PPARγ/NLRP3 pathway

Naringenin (NAR) has various biological activities but low bioavailability. The current study examines the effect of Naringenin-loaded hybridized nanoparticles (NAR-HNPs) and NAR on depression induced by streptozotocin (STZ) in rats. NAR-HNPs formula with the highest in vitro NAR released profile, lowest polydispersity index value (0.21 ± 0.02), highest entrapment efficiency (98.7 ± 2.01%), as well as an acceptable particle size and zeta potential of 415.2 ± 9.54 nm and 52.8 ± 1.04 mV, respectively, was considered the optimum formulation. It was characterized by differential scanning calorimetry, examined using a transmission electron microscope, and a stability study was conducted at different temperatures to monitor its stability efficiency showing that NAR-HNP formulation maintains stability at 4 °C. The selected formulation was subjected to an acute toxicological test, a pharmacokinetic analysis, and a Diabetes mellitus (DM) experimental model. STZ (50 mg/kg) given as a single i.p. rendered rats diabetic. Diabetic rat groups were allocated into 4 groups: one group received no treatment, while the remaining three received oral doses of unloaded HNPs, NAR (50 mg/kg), NAR-HNPs (50 mg/kg) and NAR (50 mg/kg) + peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist, GW9662 (1mg/kg, i.p.) for three weeks. Additional four non-diabetic rat groups received: distilled water (normal), free NAR, and NAR-HNPs, respectively for three weeks. NAR and NAR-HNPs reduced immobility time in forced swimming test and serum blood glucose while increasing serum insulin level. They also reduced cortical and hippocampal 5-hydroxyindoeacetic acid, 3,4-Dihydroxy-phenylacetic acid, malondialdehyde, NLR family pyrin domain containing-3 (NLRP3) and interleukin-1beta content while raised serotonin, nor-epinephrine, dopamine and glutathione level. PPAR-γ gene expression was elevated too. So, NAR and NAR-HNPs reduced DM-induced depression by influencing brain neurotransmitters and exhibiting anti-oxidant and anti-inflammatory effects through the activation PPAR-γ/ NLRP3 pathway. NAR-HNPs showed the best pharmacokinetic and therapeutic results.

Ameliorative effect of lixisenatide on diabetic cardiovascular damage and its enhancement via ticagrelor co-administration in rats: possible role of eNOS and NrF₂ /HO-1 signaling.

In this study, we hypothesized that lixisenatide (LIX) and ticagrelor (TIC) could have a protective effect against type 2 diabetes mellitus (T2DM)-induced vascular damage. Furthermore, we explored the possible additional protective effect of co-administering LIX and TIC in the treatment regimen. Methods: 50 male rats were divided into five groups, each comprising 10 rats: C (control), D (T2DM rats), D + LIX (T2DM rats treated with LIX for 4 weeks), D + TIC (T2DM rats treated with TIC for 4 weeks), and D + LIX + TIC (T2DM rats treated with LIX + TIC for 4 weeks). Results: The D group showed an increase in body weight, blood glucose, hemostatic model assessment for insulin resistance (HOMA-IR), aorta reactive oxygen species (ROS), and nuclear factor kappa B (NF-κ B), along with a reduction in serum insulin, aorta superoxide dismutase (SOD), glutathione reduced (GSH), nuclear factor erythroid-2 (NrF₂), hemeoxygenase-1 (HO-1), and endothelial nitric oxide synthase (eNOS). Deterioration in the aorta histopathological condition, coupled with a noticeable impairment in vascular reactivity compared to the C group, was observed. A single administration of LIX showed a reduction in body weight, blood glucose, HOMA-IR, aorta ROS, and NF-κ B, accompanied by an increase in serum insulin, aorta SOD, GSH, NrF₂, HO-1, and eNOS. Amelioration in the aorta histopathological condition and improved vascular reactivity compared to the D group were reported. Similarly, a single administration of TIC showed a reduction in aorta ROS and NF-κ B, along with an increase in aorta SOD, GSH, NrF₂, HO-1, and eNOS. A slight amelioration was detected in the aorta histopathological condition, with improved vascular reactivity compared to the D group. The combined administration of LIX and TIC showed a reduction in aorta ROS and NF-κ B, along with an increase in aorta GSH, SOD, HO-1, and eNOS. This was combined with evident amelioration in the aorta histopathological condition and noticeable improvement in vascular reactivity compared to the single treatment with either LIX or TIC group. Conclusion: The present study introduces clear evidence that the administration of LIX and TIC can improve metabolic and vascular complications of T2DM through modulating eNOS and NrF₂ /HO-1 signaling. The combined administration of LIX and TIC produced more significant effects than a single treatment.

#411 Magnesium deficiency abrogates the activation of Insulin-like growth factor-1 signaling pathway in the kidney induced by DPP4 inhibitor

Abstract Background and Aims Dipeptidyl peptidase-4 (DPP-4) inhibitor could attenuate cisplatin nephrotoxicity dependent on the glucagon-like peptide-1 (GLP-1) signaling pathway [1]. We had previously reported that the use of a DPP-4 inhibitor might also attenuate cisplatin nephrotoxicity in diabetic cancer patients [2], and its renoprotective effect was lost under magnesium (Mg) deficiency [3]. However, it remains to be investigated how the GLP-1 signaling pathway changes after the treatment of a DPP-4 inhibitor under Mg deficiency. The purpose of this study was to examine the changes in the downstream pathway of the GLP-1 signaling pathway after the treatment of DPP-4 inhibitor under Mg deficiency. Method Sprague Dawley rats received a Mg-deficient diet for 7 days to induce Mg deficiency (low Mg group). Control diet was given to the normal Mg group. Oral administration of a DPP-4 inhibitor was injected 1 day before sacrifice. The changes in serum active GLP-1, insulin, insulin-like growth factor (IGF-1), and the expression of their receptor in the kidney were examined. In addition, the phosphorylation of insulin/IGF-1 receptors in the kidney were investigated. Results Serum active GLP-1 increased equally in both groups with DPP-4 inhibitor administration. Renal GLP-1 receptor expression was not observed in the renal tubules. Serum IGF-1 did not change with DPP-4 inhibitor administration in the normal Mg group but increased in the low Mg group. In normal Mg group, renal IGF-1 receptor expression tended to increase with DPP-4 inhibitor administration, and its phosphorylation increased significantly. In contrast, the expression and phosphorylation of the IGF-1 receptor did not change with DPP-4 inhibitor administration in the low Mg group. The increase in serum insulin with the DPP-4 inhibitor was enhanced in the low Mg group, compared to the normal Mg group. The expression and phosphorylation of the insulin receptor did not change with DPP-4 inhibitor administration in both groups. Conclusion DPP-4 inhibitor activated the renal IGF-1 signaling pathway, but this effect disappeared under Mg deficiency. Further investigation is needed to determine whether the renal protective effect of DPP-4 inhibitor is dependent on the IGF-1 signaling pathway.

Melatonin increases AKT and SOD gene and protein expressions in diabetic rats

Diabetes mellitus (DM) is a chronic metabolic disease marked by hyperglycemia due to insulin deficiency or insulin resistance leading to many chronic complications. It is thus important to manage diabetes effectively in order to prevent and or delay these complications. Melatonin is produced by the pineal gland and regulates the wake-sleep circadian rhythm. Existing evidence suggests that melatonin may be effective in the management of DM. However, the evidence on the mechanism of the beneficial effect melatonin as a treatment for DM is limited. In this study, we investigated the effect of melatonin treatment on blood glucose, insulin (INS), AKT and superoxide dismutase (SOD) gene levels in diabetic rats. Non-diabetic and diabetic rats were treated orally for 4 weeks with either 25 mg or 50 mg/kg body weight of melatonin. At the end of the study, pancreatic and liver tissues morphology, glucose homeostasis, serum insulin and SOD levels, hepatic gene and protein expression of SOD as protecting antioxidant enzyme and AKT as central element involved in PI3K/AKT insulin signaling pathway were estimated. Melatonin treated diabetic rats showed reduced hyperglycemia, and increased serum insulin and SOD levels. In addition, melatonin induced an increased gene and protein expression of SOD and AKT. In conclusion, melatonin may play a role in treating diabetic rats via stimulation of insulin secretion, insulin signaling and reduction in oxidative stress.

Changes in Lipid and Protein Peroxidation in Blood Serum and Respiratory Lungs Homogenate in Experimental Iodine Deficiency, Insulin Resistance and Their Combination

The relevance of the study is the prevalence of diet-induced metabolic disorders, in particular, iodine deficiency and insulin resistance. The aim of the study was to find out the features of lipids and proteins peroxidation in blood serum and lung tissue in rats with iodine deficiency, insulin resistance and their combination. Thyroid profile indicators, carbohydrate metabolism markers, proteins and lipids peroxidation were determined in animals kept on a standard diet (1st, control group), iodine-deficient diet (2nd group), under high-fructose feeding conditions (3rd group) and combination of iodine deprivation and the high-fructose diet (4th group). Indicators lipids and proteins free radical oxidation were determined in serum and homogenate of the pulmonary respiratory part. Iodine insufficient diet caused hypothyroid dysfunction, as evidenced by a decrease level of thyroid hormones and increase TSH in the blood serum of rats (2nd and 4th experimental groups). Increase in serum insulin and HOMA-IR index reflects the insulin resistance (3rd and 4th groups). Long-term iodine deprivation and a high-carbohydrate diet (three months) caused a violation of thyroid homeostasis and the development of insulin resistance, which are potentiated in their combination. Under such conditions oxidative stress develops, reflecting elevation of lipid and protein peroxidation products in blood serum (by 16,40-83,10 %, р&lt;0,05) and homogenate of the respiratory pulmonary section (by 39,61 % - 2,55 times, р&lt;0,05) according to the control. Increase the intensity of peroxidation in a combination of iodine-deficient and high-carbohydrate diets suggests a synergism of comorbid pathology and an increase in bronchopulmonary risks.

(−)-Epicatechin ameliorates type 2 diabetes mellitus by reshaping the gut microbiota and Gut–Liver axis in GK rats

As one of the most abundant plant polyphenols in the human diet, (−)-epicatechin (EC) can improve insulin sensitivity and regulate glucose homeostasis. However, the primary mechanisms involved in EC anti-T2DM benefits remain unclear. The present study explored the effects of EC on the gut microbiota and liver transcriptome in type 2 diabetes mellitus (T2DM) Goto–Kakizaki rats for the first time. The findings showed that EC protected glucose homeostasis, alleviated systemic oxidative stress, relieved liver damage, and increased serum insulin. Further investigation showed that EC reshaped gut microbiota structure, including inhibiting the proliferation of lipopolysaccharide (LPS)-producing bacteria and reducing serum LPS. In addition, transcriptome analysis revealed that the insulin signaling pathway may be the core pathway of the EC anti-T2DM effect. Therefore, EC may modulate the gut microbiota and liver insulin signaling pathways by the gut–liver axis to alleviate T2DM. As a diet supplement, EC has promising potential in T2DM prevention and treatment.

Nasogastric bolus administration of a protein-rich drink augments insulinaemia and aminoacidaemia but not whole-body protein turnover or muscle protein synthesis versus oral administration.

Nasogastric feeding of protein-rich liquids is a nutritional support therapy that attenuates muscle mass loss. However, whether administration via a nasogastric tube per se augments whole-body or muscle protein anabolism compared with oral administration is unknown. Healthy participants were administered a protein-rich drink (225 ml containing 21 g protein) orally (ORAL; n=13; age 21 ± 1 year; BMI 22.2 ± 0.6 kg·m-2) or via a nasogastric tube (NG; n=13; age 21 ± 1 yr; BMI 23.9 ± 0.9 kg·m-2) in a parallel group design, balanced for sex. L-[ring-2H5]-phenylalanine and L-[3,3-2H2]-tyrosine were infused to measure postabsorptive and postprandial whole-body protein turnover. Skeletal muscle biopsies were collected at -120, 0, 120 and 300 min relative to drink administration to quantify temporal myofibrillar fractional synthetic rates (myoFSR). Drink administration increased serum insulin and plasma amino acid concentrations, and to a greater extent and duration in NG versus ORAL (all interactions P<0.05). Drink administration increased whole-body protein synthesis (P<0.01), suppressed protein breakdown (P<0.001), and created positive net protein balance (P<0.001), but to a similar degree in ORAL and NG (interactions P>0.05). Drink administration increased myoFSR from the postabsorptive state (P<0.01), regardless of route of administration in ORAL and in NG (interaction P>0.05). Nasogastric bolus administration of a protein-rich drink induces insulinaemia and aminoacidaemia to a greater extent than oral administration, but the postprandial increase in whole-body protein turnover and muscle protein synthesis was equivalent between administration routes. Nasogastric administration is a potent intervention to increase postprandial amino acid availability. Future work should assess its utility in overcoming impaired sensitivity to protein feeding, such as that seen in ageing, disuse, and critical care.

Long-Term Administration of Omeprazole-Induced Hypergastrinemia and Changed Glucose Homeostasis and Expression of Metabolism-Related Genes.

PPIs, or proton pump inhibitors, are the most widely prescribed drugs. There is a debate regarding the relationship between long-term PPI use and the risk of type 2 diabetes mellitus (T2DM). A potential connection between T2DM and PPIs could be an elevated gastrin concentration. This study is aimed at investigating the long-term effects of PPI omeprazole (OZ) on glucose homeostasis and pancreatic gene expression profile in mice. Healthy adult male BALB/c mice were randomly divided into three equal groups (n = 10 in each one): (1) experimental mice that received OZ 20 mg/kg; (2) control mice that received 30 μl saline per os; (3) intact mice without any interventions. Mice were treated for 30 weeks. Glucose homeostasis was investigated by fasting blood glucose level, oral glucose tolerance test (GTT), insulin tolerance test (ITT), and basal insulin resistance (HOMA-IR). Serum gastrin and insulin concentration were determined by ELISA. Expressions of Sirt1, Pparg, Nfκb1 (p105), Nfe2l2, Cxcl5, Smad3, H2a.z, and H3f3b were measured by RT-PCR. The ROC analysis revealed an increase in fasting blood glucose levels in OZ-treated mice in comparison with control and intact groups during the 30-week experiment. A slight but statistically significant increase in glucose tolerance and insulin sensitivity was observed in OZ-treated mice within 30 weeks of the experiment. The mice treated with OZ exhibited significant increases in serum insulin and gastrin levels, accompanied by a rise in the HOMA-IR level. These animals had a statistically significant increase in Sirt1, Pparg, and Cxcl5 mRNA expression. There were no differences in β-cell numbers between groups. Long-term OZ treatment induced hypergastrin- and hyperinsulinemia and increased expression of Sirt1, Pparg, and Cxcl5 in mouse pancreatic tissues accompanied by specific changes in glucose metabolism. The mechanism of omeprazole-induced Cxcl5 mRNA expression and its association with pancreatic cancer risk should be investigated.

Physiochemical characterization and ameliorative effect of rice resistant starch modified by heat-stable α-amylase and glucoamylase on the gut microbial community in T2DM mice.

In the presented study, natural rice containing high resistant starch content was used as a raw material to produce rice resistant starch (RRS) through enzymatic hydrolysis with heat-stable α-amylase and glucoamylase. The chemical composition, structural characteristics and in vitro glycemic index (GI) of RRS were evaluated. The effects of RRS at different doses on the body weight, serum biochemical levels, pathological indexes, production of short-chain fatty acids (SCFAs) in the gut and the intestinal microbial composition in T2DM mice were investigated. The results of physiochemical characterization indicated that, relative to rice flour, RRS mainly comprising resistant starch had higher crystallinity (25.85%) and a more stable structure, which contributed to its lower digestibility and decreased GI in vitro. Compared with the model control group, 1 g per kg BW and 2 g per kg BW oral gavage dosages of RRS effectively enhanced the SCFA productivity in the T2DM mouse gut, as well as alleviating T2DM symptoms, involving an increase in body weight, reduction in fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, alanine transaminase and aspartate aminotransferase, and an increase in serum insulin and high-density lipoprotein cholesterol. Besides, 1 g per kg BW and 2 g per kg BW dosages of RRS mitigated T2DM-induced pancreas damage. Furthermore, up-regulation in the abundance of probiotics (Lactobacillus, Ruminococcus, etc.) and down-regulation in the number of harmful bacteria (Desulfovibrio, Prevotella, etc.) were observed in all RRS-treated groups. In summary, this work suggested that RRS prepared using heat-stable α-amylase and glucoamylase could be a potential functional component for amelioration of T2DM applied in the fields of food and pharmaceutics.

Role of serotonin on pituitary-thyroid functions and antioxidants in diabetic male rats

Diabetes mellitus causes an increase in oxidative stress. Serotonin is a hormone its level in circulation reduced in diabetes; recently, it has been found to possess antioxidant qualities. The purpose of the study was to look at the impact of diabetes on pituitary-thyroid functioning, and serotonin role in modulating these effects in a streptozotocin-induced diabetes mellitus rat model. The thirty-tow healthy male rats with a body weight of 180-200 gm were split equally into 4 groups, group [1[: control, group [2]: Serotonin, group [3]: diabetic, and group [4]: Serotonin-diabetic. The rats were weighed and serum levels of glucose, insulin, malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, serotonin, thyroid stimulating hormone, thyroxine, and triiodothyronine were measured. Our results presented that there was a significant increase in T3, T4, glucose, and MDA in the diabetic group compared to the control, while a significant decrease in T3, and T4, glucose, and MDA in the Serotonin with diabetic group compared to diabetic group. Furthermore, a significant decrease in TSH, serotonin, insulin and GPX, CAT, and SOD antioxidants in the diabetic group compared to control, while a significant increase in serum TSH, serotonin, insulin and CAT, GPX and SOD antioxidants in the Serotonin+diabetic group compared to diabetic group as well as a significant increase in serum insulin in the Serotonin group compared to all other groups. Serotonin plays a protective role against diabetes-induced and pituitary-thyroid disorder caused by diabetes which might be because of its antioxidant qualities and ability to maintain glucose and insulin balance.

Impact of High-Intensity Interval Training on GLP-1R/ PKBα Axis in Pancreatic Tissue of Diabetes Rats Induced by High-Fat Diet and STZ

Objective: Apart from hormonal factors and oxidative stress, insulin synthesis is strongly dependent on transcription factors in the pancreas. The aim of the present study was to assess the impact of high-intensity interval training (HIIT) on genes affecting insulin synthesis in diabetic obese rats.&#x0D; Materials and Methods: Type 2 diabetes (T2D) was induced by a 6-week high-fat diet (HFD) and intraperitoneal injection of streptozotocin (25 mg /kg) in 14 male Wistar rats (10 week old, 220±10 g). Rats with fasting glucose levels between 400 and 150 were considered T2D. The diabetic rats were randomly assigned to exercise (HIIT: 6 weeks/5 sessions weekly, n= 7) or control (n= 7) groups. Forty-eight hours after the intervention, fasting GLP-1R and PKBα gene expression in pancreatic tissue and plasma insulin and glucose levels were compared between the groups. Data were compared by independent t-test used to compare variables, version 22 between groups. A P&lt; 0.05 was considered significant.&#x0D; Results: HIIT led to significant increase in PKBα gene expression (P: 0.001) and insulin (P: 0.031) and decreases in glucose concentration (P: 0.001) compared with the control group. No change was observed in the GLP-1R gene expression response to HIIT (P: 0.093).&#x0D; Conclusion: HIIT is associated with increased serum insulin levels in T2D obese rats. Despite no change in GLP-1R, this improvement is probably rooted in increased expression PKBα in pancreas in response to this type of exercise training

Ameliorative Effects of Cumin Extract-Encapsulated Chitosan Nanoparticles on Skeletal Muscle Atrophy and Grip Strength in Streptozotocin-Induced Diabetic Rats.

Skeletal muscle atrophy is a disorder characterized by reductions in muscle size and strength. Cumin extract (CE) possesses anti-inflammatory, antioxidant, and hypoglycemic properties. Its pharmaceutical applications are hindered by its low water solubility and by its cytotoxicity when administered at high doses. In this study, we have developed a simplified water distillation method using a rotary evaporator to isolate the active components in cumin seeds. The anti-inflammatory effects of CE and its potential to ameliorate skeletal muscle atrophy in rats with streptozotocin (STZ)-induced diabetes were evaluated. The half-maximal inhibitory concentration (IC50) of CE for cells was 80 μM. By encapsulating CE in chitosan nanoparticles (CECNs), an encapsulation efficacy of 87.1% was achieved with a slow release of 90% of CE after 24 h of culturing, resulting in CECNs with significantly reduced cytotoxicity (IC50, 1.2 mM). Both CE and CECNs significantly reduced the inflammatory response in interleukin (IL)-6 and IL-1β assays. STZ-induced diabetic rats exhibited sustained high blood glucose levels (>16.5 mmol/L), small and damaged pancreatic β islets, and skeletal muscle atrophy. CE and CECN treatments ameliorated skeletal muscle atrophy, recovered muscle fiber striated appearance, increased grip strength, and decreased IL-6 level. Furthermore, CE and CECNs led to a reduction of damage to the pancreas, restoring its morphological phenotype, increasing serum insulin levels, and lowering blood glucose levels in STZ-induced diabetic rats. Taken together, treatment with CECNs over a 6-week period yielded positive ameliorative effects in STZ-induced rats of muscle atrophy.

Mitragyna Parvifolia- Effective Against Hyper Glycaemia, Proinflammatory Markers and Liver Apoptosis in Streptozotocin Induced Diabetic Rats

Background Ethanolic extract of Mitragyna pareidolia leaves were used as a traditionally use in the treatment of diabetic conditions. The aim of the current study was to find out the effect of Mitragyna pareidolia ethanolic leaves extract (MPE) on hyperglycemia developed by streptozotocin (STZ) induced type 2 diabetes in rats. Materials and Method An animal model of diabetes type 2 was developed by administration of STZ 90 mg/Kg to two-day old neonatal rat pups. Oral glucose test and parameters were examined of diabetic rat after the different dose of extracts. The rats were existing into following groups: Group I –Normal control, Group II – STZ diabetic control, Group III –STZ Diabetic –orally administered MPEx at doses of 300 mg/kg, Group IV STZ-Diabetic – orally administered at doses of 500 mg/kg, Our study was confirmed that 8 weeks chronic treatment with MPE in a dose dependent manner (300 and 500 mg/kg) reduced hyperglycemia and significantly increased serum insulin, C-peptide. Histology of liver was performed after sacrificing the rats with euthanasia. Result The ethanolic extract of MP was not show any acute toxicity up-to the dose of 2000 mg/kg and it was shown better glucose consumption in oral glucose tolerance test. Orally treatment of different doses of MP leaves extract decreased the level of serum glucose, reduce elevated levels of tumor necrosis factor α (TNF-α), interleukin IL-6 in the serum of diabetic rats. After the study, we found that elevated blood glucose and lipids were bring back to near normal. In addition, MPE also reduce elevated levels of tumor necrosis factor α (TNF-α), interleukin IL-6 in the serum of diabetic rats. Conclusion We conclude that MPE exerted antidiabetic effects and reduced its associated complications such as dyslipidemia and inflammation. HE and confocal image of TUNEL assay showed that MPE reduced inflammation and apoptosis in diabetic rats.