Beneficial effect of flax seeds in streptozotocin (STZ) induced diabetic mice: isolation of active fraction having islet regenerative and glucosidase inhibitory properties

2013 ◽  
Vol 91 (5) ◽  
pp. 325-331 ◽  
Author(s):  
Menakshi Bhat Dusane ◽  
Bimba N. Joshi
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Immunohistochemical Analysis ◽  
Diabetic Mice ◽  
Active Fraction ◽  
Beneficial Effects ◽  
Endogenous Insulin ◽  
Flax Seeds

Diabetes mellitus is a metabolic disorder that affects millions of people worldwide. Present study highlights the antidiabetogenic property of Linum usitassimum active fraction (LU6) in streptozotocin (STZ) induced diabetic Swiss mice. Treatment with LU6 fraction showed improved glucose utilization with increase in liver glucose-6-phosphate dehydrogenase enzyme activity and normal glycogenesis in hepatic and muscle tissues. Reduction in pancreatic and intestinal glucosidase inhibitory activity was observed with LU6 treatment, indicating beneficial effects in reducing postprandial hyperglycemia (PPHG). Normalization of plasma insulin and C-peptide levels were observed in diabetic mice, indicating endogenous insulin secretion after the treatment with LU6. The histochemical and immunohistochemical analysis on pancreatic islets suggests the role of LU6 fraction in islet regeneration and insulin secretion as evident in increase functional pancreatic islets producing insulin. Furthermore, significant insulin producing islet formation was also observed in in vitro PANC-1 cells after LU6 treatment, indicating the cellular aggregates to be newly formed islets. This suggests the potential of LU6 fraction in the formation of new islets in vitro, as well as in vivo. Thus, LU6 can be used as a neutraceutical-based first-line treatment for diabetes.

Islet protective and insulin secretion property of Murraya koenigii and Ocimum tenuflorum in streptozotocin-induced diabetic mice

2012 ◽  
Vol 90 (3) ◽  
pp. 371-378 ◽  
Author(s):  
Menakshi Bhat Dusane ◽  
Bimba N. Joshi
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Immunohistochemical Analysis ◽  
Diabetic Mice ◽  
Murraya Koenigii ◽  
Cell Protection ◽  
Beneficial Effects ◽  
Endogenous Insulin ◽  
Muscle Tissues ◽  
Glucose 6 Phosphate Dehydrogenase

The present study investigates the antidiabetogenic effects of Murraya koenigii (L.) Spr. and Ocimum tenuflorum  L. on streptozotocin-induced diabetic Swiss mice. Treatment with extracts of M. koenigii (chloroform; MKC) and O. tenuflorum (aqueous; OTA) resulted in proper glucose utilization with an increase in liver glucose-6-phosphate dehydrogenase enzyme activity, and normal glycogenesis in hepatic and muscle tissues. Pancreatic and intestinal glucosidase inhibitory activity observed with MKC and OTA treatment indicated beneficial effects in reducing postprandial hyperglycemia with concomitant improvement in glucose metabolism. The glucosidase inhibition was prolonged, even after discontinuation of MKC and OTA treatment. Normalization of plasma insulin and C-peptide levels was observed in diabetic mice, indicating endogenous insulin secretion after treatment. The histochemical and immunohistochemical analysis of pancreatic islets suggests the role of MKC and OTA in pancreatic β-cell protection and the functional pancreatic islets that produce insulin. The study demonstrates the significance of MKC and OTA in glucosidase inhibition and islet protection in the murine diabetic model. These findings suggest the potential of the extracts in adjuvant therapy for the treatment of diabetes and the possible development of potential neutraceuticals.

Mice pancreatic islets protection from oxidative stress induced by single-walled carbon nanotubes through naringin

2018 ◽  
Vol 37 (12) ◽  
pp. 1268-1281 ◽  
Author(s):  
A Ahangarpour ◽  
S Alboghobeish ◽  
AA Oroojan ◽  
MA Dehghani
Keyword(s):  
Oxidative Stress ◽  
Carbon Nanotubes ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Mtt Assay ◽  
Antioxidant Defense System ◽  
Protective Effects ◽  
Cell Functions

The growing use of carbon nanotubes (CNTs) emphasizes the importance of its potential toxic effects on the human health. Previous studies proved that CNTs caused oxidative stress and decreased cell viability. On the other hand, reactive oxygen species (ROS) and oxidative stress impaired β-cell functions and reduced the insulin secretion. However, there is not any study on the effects of CNTs on islets and β-cells. Therefore, the present study aimed to evaluate the effects of single-walled CNTs (SWCNTs) on oxidative stress in islets in addition to the protective effects of naringin (NRG) as an antioxidant . We examined the effects of SWCNTs and naringin on islets by 3,4 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay; measurement of insulin secretion, ROS, and malondialdehyde (MDA); activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) peroxidase (GSH-Px); and content of GSH and mitochondrial membrane potential (MMP). The MTT assay demonstrated that decreased viability of islets cells was dose-dependent with exposure to SWCNTs. Further studies revealed that SWCNTs decreased insulin secretion and MMP, induced the formation of ROS, increased the level of MDA, and decreased the activities of SOD, GSH-Px, and CAT and content of GSH. Furthermore, the pretreatment of islets with naringin significantly reverted back these changes. These findings revealed that SWCNTs might induce the oxidative stress to pancreatic islets, causing the occurrence of diabetes, and the protective effects of naringin that was mediated by augmentation of the antioxidant defense system of islets. Our research indicated the necessity for further in vivo and in vitro researches on the effects of SWCNTs and naringin on diabetes.

scholarly journals AWRK6, a Novel GLP-1 Receptor Agonist, Attenuates Diabetes by Stimulating Insulin Secretion

2018 ◽  
Vol 19 (10) ◽  
pp. 3053
Author(s):  
Qiuyu Wang ◽  
Chunlin Zhao ◽  
Lili Jin ◽  
Hanyu Zhang ◽  
Qifan Miao ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Mass ◽  
Membrane Integrity ◽  
The Body ◽  
Oral Glucose ◽  
Diabetic Mice ◽  
Β Cell ◽  
Min6 Cells

Diabetes is a metabolic disorder leading to many complications. The treatment of diabetes mainly depends on hypoglycemic drugs, often with side effects, which drive us to develop novel agents. AWRK6 was a peptide developed from the antimicrobial peptide Dybowskin-2CDYa in our previous study, and the availability of AWRK6 on diabetes intervention was unknown. Here, in vivo and in vitro experiments were carried out to investigate the effects of AWRK6 against diabetes. In diabetic mice, induced by high-fat diet followed by streptozocin (STZ) administration, the daily administration of AWRK6 presented acute and sustained hypoglycemic effects. The plasma insulin was significantly elevated by AWRK6 during an oral glucose tolerance test (OGTT). The relative β cell mass in diabetic mice was increased by AWRK6 treatment. The body weight and food intake were remarkably reduced by AWRK6 administration. In the mouse pancreatic β cell line Min6 cells, the intracellular calcium concentration was found to be enhanced under the treatment with AWRK6, and protein kinase A (PKA) inhibitor H-89 and Epac2 inhibitor HJC0350 represented inhibitory effects of the insulinotropic function of AWRK6. By FITC-AWRK6 incubation and GLP-1 receptor (GLP-1R) knockdown, AWRK6 proved to be a novel GLP-1R agonist. In addition, AWRK6 showed no toxicity in cell viability and membrane integrity in Min6 cells, and no hypoglycemia risk and no lethal toxicity in mice. In summary, AWRK6 was found as a novel agonist of GLP-1R, which could stimulate insulin secretion to regulate blood glucose and energy metabolism, via cAMP-calcium signaling pathway, without significant toxicity. The peptide AWRK6 might become a novel candidate for diabetes treatment.

EFFECTS OF GASTRIN ON THE RELEASE OF INSULIN IN VITRO

1969 ◽  
Vol 43 (3) ◽  
pp. 371-375 ◽  
Author(s):  
A. LERNMARK ◽  
B. HELLMAN ◽  
H. G. COORE
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Glucose Concentration ◽  
Gastrointestinal Hormones ◽  
Mouse Pancreas ◽  
Low Glucose ◽  
Isolated Pancreas ◽  
Stimulation Of

SUMMARY Several investigations in vivo and in vitro have shown that gastrointestinal hormones stimulate insulin secretion. Whether gastrin also has such an effect was tested both with the isolated mouse pancreas and with micro-dissected pancreatic islets from obese-hyperglycaemic mice. A fairly low concentration of human synthetic gastrin I (0·15 μg./ml.) was found to inhibit the stimulation of insulin release normally obtained with increasing glucose concentrations. However, when a higher concentration of gastrin was tested on the isolated pancreas in the presence of a low glucose concentration there was a stimulation of insulin secretion.

Lack of long-term β-cell glucotoxicity in vitro in pancreatic islets isolated from two mouse strains (C57BL/6J; C57BL/KsJ) with different sensitivities of the β-cells to hyperglycaemia in vivo

1993 ◽  
Vol 136 (2) ◽  
pp. 289-296 ◽  
Author(s):  
C. Svensson ◽  
S. Sandler ◽  
C. Hellerström
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Insulin Biosynthesis ◽  
Mouse Strains ◽  
Β Cells ◽  
Insulin Mrna

ABSTRACT Previous studies have shown that 4 weeks after syngeneic transplantation of a suboptimal number of islets into either C57BL/6J (BL/6J) or C57BL/KsJ (BL/KsJ) diabetic mice there is an impaired insulin secretion by the perfused grafts. After normalization of the blood glucose level with a second islet graft, the BL/6J strain showed restored insulin secretion whilst that of the BL/KsJ strain remained impaired. The aim of the present work was to study the effects of glucose on the in-vitro function of islet β-cells from these two mouse strains, with different sensitivities of their β-cells to glucose in vivo. Isolated pancreatic islets from each strain were kept for 1 week in tissue culture at 5·6, 11, 28 or 56 mmol glucose/l and were subsequently analysed with regard to insulin release, (pro)-insulin and total protein biosynthesis, insulin, DNA and insulin mRNA contents and glucose metabolism. Islets from both strains cultured at 28 or 56 mmol glucose/l showed an increased accumulation of insulin in the culture medium and an enhanced glucose-stimulated insulin release compared with corresponding control islets cultured at 11 mmol glucose/l. After culture at either 5·6 or 56 mmol/l, rates of (pro)insulin biosynthesis were decreased in BL/KsJ islets in short-term incubations at 17 mmol glucose/l, whereas islets cultured at 56 mmol glucose/l showed a marked increase at 1·7 mmol glucose/l. In BL/6J islets, the (pro)insulin biosynthesis rates were similar to those of the BL/KsJ islets with one exception, namely that no decrease was observed at 56 mmol glucose/l. Islets of both strains showed a decreased insulin content after culture with 56 mmol glucose/l. Insulin mRNA content was increased in islets cultured in 28 or 56 mmol glucose/l from both mouse strains. Glucose metabolism showed no differences in the rates of glucose oxidation, however, in islets cultured in 56 mmol glucose/l the utilization of glucose was increased in both BL/6J and BL/KsJ animals. There were no differences in DNA content in islets cultured at different glucose concentrations, suggesting no enhancement of cell death. The present study indicates that, irrespective of genetic background, murine β-cells can adapt to very high glucose concentrations in vitro without any obvious signs of so-called glucotoxicity. Previously observed signs of glucotoxicity in vivo in BL/KsJ islets appear not to be related only to glucose but rather to an additional factor in the diabetic environment. Journal of Endocrinology (1993) 136, 289–296

scholarly journals Simulated Cholinergic Reinnervation ofβ(INS-1) Cells: Antidiabetic Utility of Heterotypic Pseudoislets ContainingβCell and Cholinergic Cell

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Ao Jiao ◽  
Feng Li ◽  
Chengshuo Zhang ◽  
Wu Lv ◽  
Baomin Chen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
3D Culture ◽  
Cholinergic Neurons ◽  
Fold Increase ◽  
Culture Conditions ◽  
Glucose Stimulated Insulin Secretion ◽  
E Cadherin

Cholinergic neurons can functionally support pancreatic islets in controlling blood sugar levels. However, in islet transplantation, the level of cholinergic reinnervation is significantly lower compared to orthotopic pancreatic islets. This abnormal reinnervation affects the survival and function of islet grafts. In this study, the cholinergic reinnervation of beta cells was simulated by 2D and 3D coculture of INS-1 and NG108-15 cells. In 2D culture conditions, 20 mM glucose induced a 1.24-fold increase (p<0.0001) in insulin secretion from the coculture group, while in the 3D culture condition, a 1.78-fold increase (p<0.0001) in insulin secretion from heterotypic pseudoislet group was observed. Glucose-stimulated insulin secretion (GSIS) from 2D INS-1 cells showed minimal changes when compared to 3D structures. E-cadherin expressed in INS-1 and NG108-15 cells was the key adhesion molecule for the formation of heterotypic pseudoislets. NG108-15 cells hardly affected the proliferation of INS-1 cells in vitro. Heterotypic pseudoislet transplantation recipient mice reverted to normoglycemic levels faster and had a greater blood glucose clearance compared to INS-1 pseudoislet recipient mice. In conclusion, cholinergic cells can promote insulin-secreting cells to function better in vitro and in vivo and E-cadherin plays an important role in the formation of heterotypic pseudoislets.

scholarly journals Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Hossein Rahavi ◽  
Seyed Mahmoud Hashemi ◽  
Masoud Soleimani ◽  
Jamal Mohammadi ◽  
Nader Tajik
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Dependent Manner ◽  
Diabetic Mice ◽  
Mice Model

Regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) might be applied for type 1 diabetes mellitus (T1DM) treatment. Thus, we proposed in vitro assessment of adipose tissue-derived MSCs (AT-MSCs) immunomodulation on autoimmune response along with beta cell protection in streptozotocin- (STZ-) induced diabetic C57BL/6 mice model. MSCs were extracted from abdominal adipose tissue of normal mice and cultured to proliferate. Diabetic mice were prepared by administration of multiple low-doses of streptozotocin. Pancreatic islets were isolated from normal mice and splenocytes prepared from normal and diabetic mice. Proliferation, cytokine production, and insulin secretion assays were performed in coculture experiments. AT-MSCs inhibited splenocytes proliferative response to specific (islet lysate) and nonspecific (PHA) triggers in a dose-dependent manner (P<0.05). Decreased production of proinflammatory cytokines, such as IFN-γ, IL-2, and IL-17, and increased secretion of regulatory cytokines such as TGF-β, IL-4, IL-10, and IL-13 by stimulated splenocytes were also shown in response to islet lysate or PHA stimulants (P<0.05). Finally, we demonstrated that AT-MSCs could effectively sustain viability as well as insulin secretion potential of pancreatic islets in the presence of reactive splenocytes (P<0.05). In conclusion, it seems that MSCs may provide a new horizon for T1DM cell therapy and islet transplantation in the future.

scholarly journals Altered Expression of Somatostatin Receptors in Pancreatic Islets from NOD Mice Cultured at Different Glucose ConcentrationsIn Vitroand in Islets Transplanted to Diabetic NOD MiceIn Vivo

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Eva Ludvigsen ◽  
Mats Stridsberg ◽  
Eva T. Janson ◽  
Stellan Sandler
Keyword(s):  
Pancreatic Islets ◽  
High Glucose ◽  
Somatostatin Receptors ◽  
Nod Mice ◽  
Diabetic Mice ◽  
Altered Expression ◽  
High Glucose Condition ◽  
Cell Expression

Somatostatin acts via five receptors (sst1-5). We investigated if the changes in pancreatic islet sst expression in diabetic NOD mice compared to normoglycemic mice are a consequence of hyperglycemia or the ongoing immune reaction in the pancreas. Pancreatic islets were isolated from NOD mice precultured for 5 days and further cultured for 3 days at high or low glucose before examined. Islets were also isolated from NOD mice and transplanted to normal or diabetic mice in a number not sufficient to cure hyperglycemia. After three days, the transplants were removed and stained for sst1-5and islet hormones. Overall, changes in sst islet cell expression were more common in islets cultured in high glucose concentrationin vitroas compared to the islet transplantationin vivoto diabetic mice. The beta and PP cells exhibited more frequent changes in sst expression, while the alpha and delta cells were relatively unaffected by the high glucose condition. Our findings suggest that the glucose level may alter sst expressed in islets cells; however, immune mechanisms may counteract such changes in islet sst expression.

scholarly journals Hyperglycemia downregulates Connexin36 in pancreatic islets via the upregulation of ICER-1/ICER-1γ

2013 ◽  
Vol 51 (1) ◽  
pp. 49-58 ◽  
Author(s):  
Jacques-Antoine Haefliger ◽  
Françoise Rohner-Jeanrenaud ◽  
Dorothée Caille ◽  
Anne Charollais ◽  
Paolo Meda ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Chronic Exposure ◽  
Prolonged Exposure ◽  
Mrna Levels ◽  
Adult Rats ◽  
Junction Protein ◽  
And Function

Channels formed by the gap junction protein Connexin36 (CX36) contribute to the proper control of insulin secretion. We previously demonstrated that chronic exposure to glucose decreases Cx36 levels in insulin-secreting cells in vitro. Here, we investigated whether hyperglycemia also regulates Cx36 in vivo. Using a model of continuous glucose infusion in adult rats, we showed that prolonged (24–48 h) hyperglycemia reduced the Cx36 gene Gjd2 mRNA levels in pancreatic islets. Accordingly, prolonged exposure to high glucose concentrations also reduced the expression and function of Cx36 in the rat insulin-producing INS-1E cell line. The glucose effect was blocked after inhibition of the cAMP/PKA pathway and was associated with an overexpression of the inducible cAMP early repressor ICER-1/ICER-1γ, which binds to a functional cAMP-response element in the promoter of the Cx36 gene Gjd2. The involvement of this repressor was further demonstrated using an antisense strategy of ICER-1 inhibition, which prevented glucose-induced downregulation of Cx36. The data indicate that chronic exposure to glucose alters the in vivo expression of Cx36 by the insulin-producing β-cells through ICER-1/ICER-1γ overexpression. This mechanism may contribute to the reduced glucose sensitivity and altered insulin secretion, which contribute to the pathophysiology of diabetes.

Comparison of Two Methods of Pancreas Islets Immunoisolation

1997 ◽  
Vol 20 (12) ◽  
pp. 701-703 ◽  
Author(s):  
T. Orłowski ◽  
E. Sitarek ◽  
K. Tatarkiewicz ◽  
M. Sabat ◽  
M. Antosiak
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Diabetic Mice ◽  
In Vitro Methods ◽  
Glucose Challenge ◽  
In Vitro Insulin Secretion ◽  
Islets Transplantation

The efficacy of two methods of Langerhans islets immunoisolation was compared. For this purpose the function of islets encapsulated with alginate/polyethylenimine/protamine/heparin (APPH) or with alginate/poly-L-lisine/alginate (APA) membranes was assessed: in vitro according to their survival and response to glucose challenges, and in vivo according to their capability to provide sufficient insulin delivery to maintain normal fasting blood glucose following xenotransplantation to streptozotocin diabetic mice. In vitro insulin secretion and the response to glucose challenge of APPH and APA encapsulated islets were comparable to free islets. In vivo intraperitoneal concordant xenotransplantation of APA encapsulated rat islets reversed the diabetic state of streptozotocin diabetic mice for a longer period, than APPH islet grafts. This study clearly demonstrated the inadequacy of in vitro methods in the prediction of in vivo results of islets transplantation.

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