Insulin In Rats Research Articles

Effect of Prosopis ruscifolia on incretin and insulin secretion in alloxan-induced hyperglycemic rats

Background: Diabetes mellitus treatment is based on oral hypoglycemic agents or insulin. Medicinal plants constitute an option, and the leaves of Prosopis ruscifolia (Pr) were shown to be effective in reducing glycemia in hyperglycemic animals. Objective: In this paper, we report the effect of P. rusciofolia (Pr) on insulin and incretin secretion in alloxan-induced hyperglycemic rats. Methodology: The effective dose was selected, and four groups (n=10) of Wistar rats were used. Two groups with normal glycemia received water or Pr (75 mg/Kg, per os, p.o.), and two groups with hyperglycemia induced by alloxan (intraperitoneal, ip), received water or Pr (75 mg/Kg, p.o.) for 2 weeks. Oral glucose tolerance test, and incretin and insulin levels were measured at the end of the experimental period. Results: The results showed that extract promotes better tolerance to oral glucose overload, in addition to a statistically significant (p<0.001) increase in blood levels of incretin and insulin, compared to the hyperglycemic rats. Conclusion: It is concluded that the ethanolic extract of P. ruscifolia leaves has a hypoglycemic effect in hyperglycemic animals by a mechanism that involves the incretin-insulin system.

Effect of Synbiotics on Lipid Profile and Serum Levels of Gonadotropins, Insulin and Glucose in Rats with Polycystic Ovary Syndrome Induced by Lipopolysaccharide

Background: In women of childbearing age, Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder. The cause of PCOS is still unknown and several factors may be involved. Objective: This study aims to evaluate the effect of synbiotics on serum parameters such as Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), triglyceride, cholesterol, glucose, and insulin in rats with PCOS. Methods: In this study, 40 adult female Wistar rats weighing approximately 180-200 g were randomly divided into five groups of control, PCOS, PCOS+LPS, PCOS+Synbiotic, PCOS+LPS+Synbiotic. To induce PCOS, rats were treated with Lipopolysaccharide (LPS) for 21 days. At the end, serum levels of LH, FSH, and insulin were measured by the ELISA method, and blood glucose, cholesterol, and triglyceride levels were measured by the enzymatic method. The results were analyzed in SPSS v. 22 software using one-way ANOVA and Tukey’s Post Hoc test. Results: The levels of triglycerides, cholesterol, insulin, glucose, FSH, and LH in the PCOS and PCOS+LPS groups were significantly higher compared to the control group (P<0.05). Treatment with synbiotics in the intervention groups caused a significant reduction in all variables (P<0.05). Conclusion: Synbiotics have beneficial effects on the improvement of lipid profile, gonadotropins, insulin, and glucose levels in PCOS rats induced by LPS.

Impact of Mulberry Leaf Extract and Mulberry Leaf Powder on Serum Nesfatin-1 Level in Nicotinamide/Streptozotocin-Induced Type 2 Diabetic Rats

Background & Objective: In traditional medicine, leaves of white mulberry (Morus alba L.) are used as antidiabetic agents. Considering the presence of flavonoids, this plant exhibits insulin mimetic activities. Nesfatin-1 is described as an anorexigenic regulatory peptide, which can influence glucose metabolism via insulin sensitivity enhancement. This study examined the effects of both mulberry leaf powder and extract (MLP and MLE) on fasting blood glucose (FBG), nesfatin-1, and insulin in diabetic Wistar rats. Materials & Methods: Five groups of rats (n, 40) were included and examined in this study. A group was selected as the healthy control (I), while the other groups received streptozotocin and nicotinamide (55 and 110 mg/kg bw, respectively) for diabetes induction. Diabetic rats were then grouped as follows: control group (II); sham group (receiving ethanol) (III); treatment group receiving 600 mg/kg/day of MLE (IV); and treatment group receiving 25% MLP (V). After 6 weeks, we measured insulin, nesfatin-1, and FBG in the groups. Results: The FBG level decreased in the treatment groups, while serum insulin increased in comparison with the diabetic controls. In addition, serum level of nesfatin-1 improved significantly (to an almost normal level) in MLP rats in comparison with the diabetic controls. (pvalue<0.05) The effects of MLE on serum nesfatin-1 was similar to MLP but not significant. (pvalue>0.05) Conclusion: Considering the reduction in insulin level and the rise in blood glucose, the diabetic control group showed an increase in serum nesfatin-1 with a compensatory mechanism, while hyperglycemia improved in the MLE and MLP groups, and the level of nesfatin-1 reduced. MLP showed greater efficacy than MLE in the improvement of nesfatin-1, which might be related to the presence of ethanol in MLE.

A high carbohydrate and soda diet influences metabolic variables in Wistar rats

AimsHigh carbohydrate diet and carbonated soda consumption have individually been associated with metabolic dysfunction, with links to glucose and insulin homeostasis, affecting metabolic variables associated with feeding, satiety and adiposity. Our objective is to determine the combined effect of a high carbohydrate and carbonated soda diet on metabolic variables in male and female Wistar rats. Materials and methodsThirty-two female and male weanlings were equally divided into four dietary groups; Control, Soda, High Carbohydrate diet (HCD), and High Carbohydrate diet/Soda (HCD/Soda), and fed ad libitum for fourteen weeks. Bodyweight, thoracic circumference, abdominal circumference and glucose was determined; Insulin, leptin, adiponectin, Tumor Necrotic Factor (TNF)-α, Interleukin (IL)-6 and lipid profile were assayed and used to determine the metabolic effects. Key findingsSoda and HCD/Soda had increased body weight in male rats, while HCD-fed rats were reduced compared to respective controls. Abdominal circumference, total cholesterol and reduced HDL of Soda were elevated in both sexes. Although HCD/Soda groups had elevated abdominal circumference in both sexes, total cholesterol and reduced high-density lipoprotein (HDL) were both reduced in females. Insulin and malondialdehyde (MDA) concentrations in Soda-fed rats was significantly reduced, however, MDA was elevated in both sexes in HCD and HCD/Soda fed rats. Female HCD and HCD/Soda groups had a significant increase in glutathione (GSH) concentration and a significant reduction in catalase. TNF-α was increased in both Soda and HCD/Soda groups. SignificanceThe results of this study suggest that HCD and Soda consumption results in alteration in phenotype and variables impacting metabolism.

The role of hesperidin in ameliorating retinal changes in rats with experimentally induced type 1 diabetes mellitus and the active role of vascular endothelial growth factor and glial fibrillary acidic protein.

Patients with type 1 diabetes mellitus (T1DM) are vulnerable to developing diabetic retinopathy even under insulin therapy. Thus, this study was designed to evaluate the efficacy of hesperidin and insulin in rats with T1DM compared with insulin alone in improving diabetic retinal changes. Eighty rats were divided into four equal groups: group I, control rats without diabetes; group II, untreated rats with diabetes; group III, rats with diabetes treated daily with subcutaneous (SC) doses of long-acting insulin; and group IV, a rat with diabetes in which hesperidin was orally administered with SC insulin. The animals were assessed histologically, morphometrically, and biochemically. In group II, the thickness of all retinal layers decreased histologically. Ultrastructurally, degenerated retinal neurons and congested blood vessels were observed. Immunostaining detected elevated gene expression of advanced glycation end products. Gene expression of vascular endothelial growth factor, and glial fibrillary acidic protein were elevated. In this study, hesperidin supplementation with insulin significantly improved the retinal histological changes, supported by morphometric findings, compared with insulin alone. Moreover, treatment with hesperidin significantly reduced malondialdehyde and elevated serum antioxidant markers, including superoxide dismutase and catalase; furthermore, glutathione peroxidase decreased. Hesperidin might be an effective supplement for improving diabetic retinal complications occurring even with insulin treatment.

Pharmacodynamic and pharmacokinetic interaction of losartan with glimepiride-metformin combination in rats and rabbits.

OBJECTIVES:The presence of comorbidities such as cardiovascular disease, peripheral vascular disease, and chronic renal disease, or and the prevention of these ailments in diabetics, frequently demands multiple drug treatments, increasing the risk of drug-drug interactions (DDIs). The current study was focused on identifying possible DDIs on concomitant administration of losartan, a drug used to regulate hypertension along with a combination of glimepiride + metformin, widely used to treat diabetes mellitus. Possible pharmacodynamic and pharmacokinetic interactions were observed for, following single-dose as well as multiple-dose treatment protocols in normal and alloxan-induced diabetes in albino Wistar rats and rabbits.MATERIALS AND METHODS:Blood samples from surviving rats/rabbits obtained through orbital venous sinus bleeding/marginal ear vein bleeding, respectively, at predetermined intervals and put through to biochemical estimations of sugar level in the blood by Glucose oxidase/peroxidase method; insulin levels in serum using the enzyme-linked immunosorbent assay and serum glimepiride levels using the high-performance liquid chromatography.RESULTS AND DISCUSSION:Losartan, when treated as a single drug, resulted in a slight lowering of blood glucose levels in normal rats, diabetic rats and normal rabbits. Hypoglycemic activity of a combination of glimepiride + metformin was enhanced when losartan was co-administered as a single dosage schedule as well as a multiple dose schedule as indicated by a reduced blood glucose level and enhanced levels of insulin in rats as well as in rabbits. Serum glimepiride levels were also higher and pharmacokinetic parameters of glimepiride including mean residence time, Cmax, T1/2, AUMC0-∞, AUMC0-t, and AUC0-∞, were significantly higher, whereas its clearance was decreased in the two regimens of losartan that was followed.CONCLUSION:It can therefore be concluded, that in diabetics with hypertension as a comorbidity condition, co-administration of losartan with glimepiride + metformin should be avoided or the dosage of a combination of glimepiride + metformin needs to be tittered to avoid recurrence of hypoglycemic episodes.

Age-related features of developing insulin resistance and adipocyte sensitivity to insulin in rats with induced metabolic syndrome

Old age and insulin resistance accompanying metabolic syndrome are significant factors in the development of cardiovascular pathology.Aim. The aim of the study was to identify the age-related characteristics of developing insulin resistance on the body level and insulin resistance in rat adipocytes in animals with induced metabolic syndrome.Material and Methods. The study was carried out on male Wistar rats, which were divided into the following groups: group 1 (n = 14) comprised intact rats aged 150 days at the end of study; group 2 (n = 14) comprised rats aged 150 days at the end of 90-day period on diet with high contents of carbohydrates and fats (HCHFD); group 3 (n = 14) comprised intact rats aged 540 days at the end of the study; group 4 (n = 14) comprised rats aged 540 days after the end of 90-day HCHFD. Diet composition was as follows: 16% proteins, 21% fats, 46% carbohydrates including 17% fructose, 0.125% cholesterol, and replacement of drinking water with a 20%-fructose solution. At the end of the diet, body and organ weights were measured, and contents of glucose, insulin, triglycerides, serum leptin, and liver triglycerides were assessed. Epididymal adipose tissue adipocytes were isolated enzymatically. The content of reactive oxygen species (ROS) was investigated using 2,3-dihydrodichlorofluorescein diacetate. Increased ROS production and lipolysis inhibition in response to insulin were observed.Results. The signs of metabolic syndrome were observed in both age groups of HCHFD animals and included visceral obesity, hyperglycemia, and insulin resistance measured by homeostatic model assessment of insulin resistance (HOMA-IR). However, the obesity indicators were more pronounced in the group of young rats, whereas the signs of insulin resistance prevailed in older rats. Leptinemia directly correlated with HOMA-IR (rSp = 0.485, p = 0.03). Insulin resistance of adipocytes was observed in rats older than 540 days after the HCHFD.Conclusion. The obtained results suggested that age was a risk factor for the development of insulin resistance on the body level. Aging resulted in a decrease in the adipocyte sensitivity to insulin in metabolic syndrome. An increase in leptin may be a possible mechanism for worsening of insulin resistance with age.

Effect of Allium sativum extract in combination -with orlistat on insulin resistance and disrupted metabolic hormones in high fat diet induced obese rats

Obesity has increased in epidemic proportions globally and the current antiobesity drugs have treatment limitations which further reduce treatment benefits. The aim of this study was to evaluate the effect of Allium sativum and Orlistat on insulin resistance, fatty acid content and metabolic hormones; leptin, ghrelin and adiponectin in high-fat diet-induced obese rat model. The sprague-dawley rats used in this study were fed with standard chow as control diet, Fat emulsion as high-fat diet (HFD), HFD+ Orlistat, HFD+ A. sativum extract and HFD+ Orlistat+ A. sativum extract. Free fatty acid, serum glucose, insulin, leptin, ghrelin, adiponectin, and Homeostasis model assessment for insulin resistance (HOMA-IR) index were determined using standard methods. HFD significantly increased (P < .001) body weight, serum glucose, free fatty acid content, serum insulin, HOMA-IR and serum leptin. Furthermore, HFD reduced the serum levels of ghrelin and adiponectin when compared to control rats. The combined administration of A. sativum and orlistat resulted in a decrease in the body weight and HOMA-IR and also improved serum levels of glucose, insulin, leptin, ghrelin and adiponectin in obese rats fed with HFD. This suggests A. sativum in combination with orlistat, has the potential to ameliorate insulin resistance and metabolic hormones disrupted by obesity

Hypoglycemic and Vasorelaxant Effect of Passiflora edulis Fruit Peel By-Product.

Passiflora edulis fo. flavicarpa (Passifloraceae) is popularly known as yellow passion fruit and its fruit peels are considered a rich by-product in bioactive compounds which has greatly beneficial health properties. The objective of this study was to evaluate the effects of P. edulis fruit peel extracts in a type 1 diabetes model and the potential vasorelaxant effect. The aqueous and hydroethanolic extracts were obtained from P. edulis fruit peels and orientin and isorientin flavonoids were identified in both extracts through ultra-high performance liquid chromatography. Pectin was only identified in the aqueous extract by high-performance steric exclusion chromatography and nuclear magnetic resonance. Regarding the vascular system, the hydroethanolic extract showed better vasorelaxant effects in the mesenteric artery rings when compared to the aqueous extract. These effects mainly occur by opening the potassium channels. In the type 1 diabetes model, extracts at doses of 400 and 600mg/kg were able to restore the effect of insulin in diabetic rats which were not responding to its action. The antidiabetic effect was more significant for the aqueous extract. Thus, the results suggest that the hydroethanolic and aqueous extracts have greater potential to be used to treat cardiovascular diseases such as hypertension and as a hypoglycemic agent, respectively. Taken together, P. edulis fruit peel extracts proved to be a source of valuable bioactive raw material to produce nutraceuticals or pharmaceutical products.

Effects and Mechanism of Zishen Jiangtang Pill on Diabetic Osteoporosis Rats Based on Proteomic Analysis.

Objective To explore the effect and mechanism of ZJP on DOP rats by proteomic analysis. Materials and Methods After the establishment of diabetes model by Streptozocin (STZ, 60 mg/kg), 40 Wistar rats were equally divided into normal group, model group (diabetic rats), high-dose group (3.0 g/kg/d ZJP), and low-dose group (1.5 g/kg/d ZJP) and received treatment for 3 months. Histological changes in bone and pancreas tissues were observed by hematoxylin and eosin staining, electron microscopy, and immunofluorescence. Proteomic and bioinformatic analyses were performed to identify the differentially expressed proteins. The fingerprint and active ingredients of ZJP were identified via high-performance liquid chromatography (HPLC). Results Compared with the model group, ZJP could rescue the weight, fasting blood glucose, and fasting insulin of rats in both high-dose and low-dose group. ZJP could also improve the microstructures of pancreatic islet cells, bone mass, and trabecular and marrow cavities in DOP rats. Bioinformatic analysis suggested that ZJP might influence DOP via multiple pathways, mainly including ribosomes, vitamin digestion and absorption, and fat digestion and absorption. The primary active ingredients, including notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, icariin, and ginsenoside Rb1, were detected. Conclusion ZJP could significantly improve the histomorphology and ultrastructure of bone and islets tissues and might serve as an effective alternative medicine for the treatment of DOP.

Antioxidant Total and HOMA-IR of Diabetic Rats Given Crocatum piper and Andrographis paniculata Leaf Extracts

Background: Type-2 diabetes mellitus (T2DM) is a silent killer which the prevalence continues to increase in every year. Increased oxidative stress occurs in T2DM. Red betel and bitter herb leaf extracts (RBBH) contain a lot of antioxidants. This combination is expected to provide better safety than if used singly because the content of andrographolid in bitter herb has effect such as nausea, vomiting, loss of appetite, and antifertility if consumed in high doses.Objective: The study aimed to prove the effect of red betel and bitter herb leaf extracts on antioxidant total and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in T2DM rats given high-fat diet and Streptozotocin (STZ) induction.Methods: Experimental randomized study with pre-post-test control group design using 25 Sprague Dawley male rats. T2DM model was conducted by providing high-fat feed for 14 days and induction of Streptozotocin-Nicotinamide, then given a combination of red betel and bitter herb leaf extracts at doses of 237.5 mg/kg BW, 225 mg/kg BW, and 212.5 mg/kg BW for 21 days. The measurement of antioxidant total used 2,2-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) method. HOMA-IR measured by ELISA (Enzyme-linked immunosorbent assay) method using insulin level equation and fasting blood glucose level measured by glucose oxidase-peroxidase aminoantrypirin (GOD-PAP). Data analysis used paired t-test, wilcoxon test, and ANOVA test to analyze differences in antioxidant total and HOMA-IR value among groups and followed by Bonferroni post-hoc test.Results: All treatments could reduce HOMA-IR and significantly increase antioxidant total (p&lt;0.05). The most decrease in HOMA-IR and increase in antioxidant total at dose 237.5 mg/kg BW of red betel and bitter herb leaf extracts.Conclusion: The combination of red betel and bitter herb leaf extracts with dose 237.5 mg/kg BW, 225 mg/kg BW, and 212.5 mg/kg BW can improve blood glucose, insulin, and HOMA-IR levels in type-2 diabetes mellitus rats.

Genetically determined exercise capacity affects systemic glucose response to insulin in rats.

Aerobic exercise capacity is inversely related to morbidity and mortality as well as to insulin resistance. However, exercising in patients has led to conflicting results, presumably because aerobic exercise capacity consists of intrinsic (genetically determined) and extrinsic (environmentally determined) parts. The contribution of both parts to insulin sensitivity is also not clear. We investigated sedentary and exercised (aerobic interval training) high-capacity runners (HCR) and low-capacity runners (LCR) differing in their genetically determined aerobic exercise capacity to determine the contribution of both parts to insulin sensitivity. LCR and HCR differed in their untrained exercise capacity and body weight. Sedentary LCR displayed a diabetic phenotype with higher random glucose, lower glucose infusion rate during hyperinsulinemic euglycemic clamping than HCR. Echocardiography showed equal morphological and functional parameters and no change with exercise. Four week of exercise caused significant improvements in aerobic exercise capacity, which was more pronounced in LCR. However, with respect to glucose use, exercise affected HCR only. In these animals, exercise increased 2-deoxyglucose uptake in gastrocnemius (+58.5%, P = 0.1) and in epididymal fat (+106%; P < 0.05). Citrate synthase activity also increased in these tissues (gastrocnemius 69% epididymal fat 63%). In our model of HCR and LCR, genetic predisposition for low exercise capacity is associated with impaired insulin sensitivity and impedes exercise-induced improvements in insulin response. Our results suggest that genetic predisposition for low aerobic exercise capacity impairs insulin response, which may not be overcome by exercise.

Fabrication of novel-shaped microneedles to overcome the disadvantages of solid microneedles for the transdermal delivery of insulin.

In this study, we fabricated two different microneedles (MNs) - semi-hollow and bird-bill - to overcome the limitations of solid and coated MNs, respectively. The two MN arrays were developed using a general injection molding process to obtain high-quality MNs with uniform shape. The semi-hollow and bird-bill MNs could penetrate the micropores of swine skin up to depths of 178.5 ± 27.6µm and 232.1 ± 51.3µm, respectively. When the semi-hollow MNs were used for the transdermal delivery of insulin in diabetic rats, it was observed that the blood glucose concentration (BGC) decreased remarkably within 30min, and the desired effect of insulin was maintained for an additional 3h after the removal of insulin from the skin surface. The bird-bill MN was able to load a coating gel at a maximum capacity of 3.20 ± 0.21mg per MN array, and the BGC continued to decrease significantly after MN application for up to 2-6h. In summary, we fabricated semi-hollow and bird-bill MN arrays using the injection molding method; these can be mass produced and are capable of effectively producing micro-holes in the stratum corneum. The two MN arrays could provide effective transdermal delivery of large-molecular-weight drugs such as insulin.

Effects of experimental colitis in rats on incretin levels, inflammatory markers, and enteric neuronal function.

IntroductionThe aim of the study was to assess the effects of chronic inflammation on incretin levels, inflammatory markers, and enteric neuronal function measured in isolated preparations of smooth muscle of rat.Material and methodsWe induced experimental colitis using 2,4-dinitrobenzenesulfonic acid (DNBS) in 17 Albino male Sprague-Dawley rats, while 16 rats were used as a control. They were housed in temperature-controlled rooms in a 12-h light/dark cycle at 22–24°C and 50 to 60% humidity. We evaluated in both inflamed and healthy rats: fasting plasma glucose concentration, fasting plasma insulin, myeloperoxidase, active glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), and GLP-2 levels, adiponectin, and C-reactive protein (CRP). We also evaluated colonic longitudinal smooth muscle contractile activity.ResultsIntrarectal administration of DNBS reduced body weight gain in inflamed rats. We recorded higher levels of fasting plasma glucose, and insulin in inflamed rats. We observed higher levels of myeloperoxidase and CRP, and lower levels of ADN in inflamed rats. We recorded higher levels of GIP, GLP-1, and GLP-2 in inflamed rats compared to the healthy ones. Regarding functional response of colon intestinal smooth muscle after electrical stimulation, we recorded a lower functional response of colon intestinal smooth muscle after electrical stimulation in inflamed rats.ConclusionsWe can conclude that chronic inflammation leads to an increase of incretin levels and to a decrease of functional response of colon intestinal smooth muscle after electrical stimulation.

Synthesis of a novel glibenclamide-pioglitazone hybrid compound and its effects on glucose homeostasis in normal and insulin-resistant rats

A new library of hybrid compounds that combine the functional parts of glibenclamide and pioglitazone was designed and developed. Compounds were screened for their antihyperglycemic effects on the glucose tolerance curve. This approach provided a single molecule that optimizes the pharmacological activities of two drugs used for the treatment of diabetes mellitus type 2 (DM2) and that have distinct biological activities, potentially minimizing the adverse effects of the original drugs. From a total of 15 compounds, 7 were evaluated in vivo; the compound 2; 4- [2- (2-phenyl-4-oxo-1,3-thiazolidin-3-yl) ethyl] benzene-1-sulfonamide (PTEBS) was selected to study its mechanism of action on glucose and lipid homeostasis in acute and chronic animal models related to DM2. PTEBS reduced glycemia and increased serum insulin in hyperglycemic rats, and elevated in vitro insulin production from isolated pancreatic islets. This compound increased the glycogen content in hepatic and muscular tissue. Moreover, PTEBS stimulated the uptake of glucose in soleus muscle through a signaling pathway similar to that of insulin, stimulating translocation and protein synthesis of glucose transporter 4 (GLUT4). PTEBS was effective in increasing insulin sensitivity in resistance rats by stimulating increased muscle glucose uptake, among other mechanisms. In addition, this compound reduced total triglycerides in a tolerance test to lipids and reduced advanced glycation end products (AGES), without altering lactate dehydrogenase (LDH) activity. Thus, we suggest that PTEBS may have similar effects to the respective prototypes, which may improve the therapeutic efficacy of these molecules and decrease adverse effects in the long-term.

Possible Short-Term Biological Effects of Kefir Beverage: Ⅰ: Effect of Kefir Beverage on The Cell Biological, Histochemical, Histopathological and Biochemical Changes in Pancreas of High Fat-Fed STZ- Induced Diabetic Male Wistar Rat

The present study was designed to investigate the biological effects of kefir and whether kefir consumption protects and/or repairs the pancreas of high-fat diet-fed streptozotocin-diabetic rats, and how does it do that?. Our results showed Kefir decreased both the volume of nuclei and RNA content and increased both collagen and lipoproteins material contents in the normal pancreatic cells. Also, kefir increased RNA, protein, and lipoproteins materials content and decreased the volume of nuclei of pancreatic cells in diabetic male rats. Immunohistochemically, kefir showed highly immunoreactive signals of insulin granules inside the Langerhans Islands. Our results showed kefir consumption had a beneficial effect on controlling the glycemic state in diabetic rats by lowering insulin levels and kept the pancreas tissue structurally almost normal. Kefir probably acts as follows: From the cell biological and histochemical points of view, the results showed an increase in the nuclei volume and DNA, RNA, and total protein contents in the pancreatic cells of diabetic rats treated with kefir. Also, the biochemical and immunohistochemical results showed an increase in insulin hormone (functional protein) of these pancreatic cells, which’s probably a result of an increase in the cellular activities or/and the number of beta cells. Finally, therefore we propose that kefir has a stimulatory effect on the cellular activity of beta cells leading to activation of genes responsible for the protein synthesis included insulin hormone, and/or increasing the cell proliferation of beta cells in the pancreas of diabetic rats. From Cell biological, Histochemical, Immunohistochemical, pathological, and Biochemical points of view, the preclinical treatment with kefir or insulin of normal or diabetic male rats, beneficially highly alternates the cellular activities, histochemical and immunohistochemical materials components, and histological architecture. of the pancreas therefore Kefir and insulin may, to some extent, repair the pathological side effects of type 1 diabetes mellitus. The positive results of using kefir and insulin in treating the Pathogen effects of type 1 diabetes mellitus on the pancreas of male mice gave us a hope of possibility to obtain positive clinical applications/implications. Therefore, these positive beneficial results make us continue our work and complete the various pre-clinical trial and clinical experiments phases.

Liraglutide inhibits the progression of prediabetes in rats by reducing Raf-1 kinase inhibitor protein.

BackgroundThe cleavage product of Raf-1 kinase inhibitor protein (RKIP), hippocampal cholinergic neurostimulating peptide (HCNP) is involved in the promotion of insulin secretion. Studies have shown that liraglutide can inhibit the progression of prediabetes. This study aims to investigate whether the above effects of liraglutide are related to RKIP and HCNP.MethodsInsulin-1 (INS-1) cells were divided into control group (CON), HCNP group, and HCNP + darifenacin group (H-DAR). The three groups were cultured with Roswell Park Memorial Institute (RPMI) 1640, synthetic HCNP (50 pg/mL) and RPMI 1640, and HCNP + RPMI 1640 + darifenacin respectively. Subsequently, twelve 12- to 14-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomly divided into 2 groups: the placebo group (PBO) and the liraglutide treatment group (LIRA). Six Long Evans Tokushima Otsuka (LETO) rats were used as the control group (CON). The LIRA group was given liraglutide 200 µg/kg intraperitoneally twice a day. After 12 weeks, body weight, fasting blood glucose, 2 hours postprandial blood glucose, and insulin resistance index were recorded. Western blot was used to detect expression level of C-RKIP, N-RKIP, and extracellular signal-regulated kinase of phosphorylation (p-ERK). Real-time quantitative polymerase chain reaction (qRT-PCR) to detect pancreatic tissue choline acetyltransferase (ChAT) and M3 cholinergic receptor (M3R) gene expression levels.ResultsAt glucose concentrations of 5.6 and 16.7 mmol/L, the insulin content in the HCNP group was higher than that in the CON and H-DAR groups (all P<0.01). The body weight and fasting serum insulin (FINS) of rats in the PBO group were higher than those in the LIRA group and the CON group (P<0.01). The relative content of C-RKIP protein in the PBO group was higher than that in the LIRA and CON groups (P<0.01). The relative content of N-RKIP protein and p-ERK protein was lower than that in the LIRA and CON group (P<0.05 and P<0.01, respectively). ChAT and M3R gene expression levels in PBO group were lower than those in LIRA and CON group (P<0.01).ConclusionsLiraglutide promotes the production of HCNP, can increase ChAT activity, activate M3R, and further promote the secretion of insulin.

Effect of vanadium (IV) chloride supplementation on appetite-related hormone levels in rats with experimentally induced diabetes

Vanadium is one of the essential trace elements for mammals, which has important functions in the metabolism of carbohydrates. There is limited data about the effects of vanadium (IV) chloride supplementation on appetite-related hormones in literature. Our target was to analyse the impacts of vanadium supplementation on appetite-related hormone (leptin, nesfatin-1 and apelin) levels in rats with experimentally induced diabetes. Twenty eight male Sprague-Dawley albino rats were used in this study. After formation of diabetes, 0.3 mg/mL of vanadium was added to drinking water of rats for four weeks. A substantial increment was found in serum glucose (p < 0.001), HbA1c (p < 0.001), HOMA-IR (p < 0.01), and leptin (p < 0.001) levels and a significant decrease in insulin, apelin and nesfatin-1 concentrations in diabetic rats. Moreover, blood glucose, HbA1c, HOMA-IR, and leptin levels decreased in diabetic + vanadium group, but nesfatin-1 (1.74 ± 0.94 ng/mL), apelin (1.74 ± 0.94 ng/mL), and insulin concentrations were found higher compared with the diabetic group. As a result of this study, vanadium has increased the levels of circulating nesfatin-1 and apelin levels in diabetic rats while decreasing blood glucose and leptin concentrations. But further studies are required to determine the blood glucose lowering effects of vanadium and its relationship with appetite related hormones in diabet.

Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of Acacia arabica Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents.

Acacia arabica is used traditionally to treat a variety of ailments, including diabetes. This study elucidated the antidiabetic actions of A. arabica bark together with the isolation of bioactive molecules. Insulin secretion and signal transduction were measured using clonal β cells and mouse islets. Glucose uptake was assessed using 3T3-L1 adipocytes, and in vitro systems assessed additional glucose-lowering actions. High-fat-fed (HFF) obese rats were used for in vivo evaluation, and phytoconstituents were isolated and characterised by RP-HPLC followed by LC-MS and NMR. Hot-water extract of A. arabica (HWAA) increased insulin release from clonal β cells and mouse islets by 1.3–6.8-fold and 1.6–3.2-fold, respectively. Diazoxide, verapamil and calcium-free conditions decreased insulin-secretory activity by 30–42%. In contrast, isobutylmethylxanthine (IBMX), tolbutamide and 30 mM KCl potentiated the insulin-secretory effects. The mechanism of actions of HWAA involved membrane depolarisation and elevation of intracellular Ca2+ together with an increase in glucose uptake by 3T3-L1 adipocytes, inhibition of starch digestion, glucose diffusion, dipeptidyl peptidase-IV (DPP-IV) enzyme activity and protein glycation. Acute HWAA administration (250 mg/5 mL/kg) enhanced glucose tolerance and plasma insulin in HFF obese rats. Administration of HWAA (250 mg/5 mL/kg) for 9 days improved glucose homeostasis and β-cell functions, thereby improving glycaemic control, and circulating insulin. Isolated phytoconstituents, including quercetin and kaempferol, increased insulin secretion in vitro and improved glucose tolerance. The results indicate that HWAA has the potential to treat type 2 diabetes as a dietary supplement or as a source of antidiabetic agents, including quercetin and kaempferol.

Insulin-producing cells from bone marrow stem cells versus injectable insulin for the treatment of rats with type I diabetes

Recently, stem cells have been considered renewable cell sources in the treatment of diabetes and the development of insulin-producing cells. In this regard, the current study aimed to compare Insulin-producing cells from bone marrow stem cells with injectable insulin in rats with type I diabetes. For this purpose, 40 rats were divided into four groups: the control or healthy group, the diabetic control group, the group that received differentiated insulin-producing cells from bone marrow, and the group that received insulin treatment. To differentiate insulin-producing cells from bone marrow, the femoral bone marrow of rats was extracted using the flushing method. Differentiated cells were evaluated using dithizone-specific dye, anti-insulin-proinsulin antibodies, and anti-insulin beta receptors. Also, the expression of the pdx-I gene, as the specific gene of pancreatic cells, was examined by RT-PCR. The results showed that transplantation of insulin-producing cells could significantly increase blood insulin levels in diabetic rats. This increase intensified in the second stage of transplantation when more cells were injected into rats. Concerning decreasing blood sugar levels, differentiated cells were able to reduce blood sugar levels significantly. Even in the first stage of cell injection, in which the rats received a small number of cells, their blood sugar levels were controlled by these cells. As a result, the present study showed that repeated transplants of insulin-producing cells differentiated from bone marrow could decrease blood sugar and increase insulin levels.