In vivo endotoxin and IL-1 potentiate insulin secretion in pancreatic islets

1990 ◽  
Vol 258 (4) ◽  
pp. R1070-R1077 ◽  
Author(s):  
M. R. Yelich
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Interleukin 1 ◽  
Similar Extent ◽  
Isolated Pancreatic Islets ◽  
In Vitro Insulin Secretion ◽  
In Vivo Effects ◽  
Insulin Secretory Response

This study evaluated the in vivo effects of endotoxin and interleukin 1 (IL-1) on in vitro insulin secretion from perfused rat pancreases and isolated pancreatic islets. Glucose-induced insulin secretion was potentiated in pancreases obtained from rats 3 h after endotoxin or 30 min after IL-1. Studies using isolated pancreatic islets indicated that islet sensitivity to glucose was increased by either endotoxin or IL-1 to a similar extent, but there was no effect of endotoxin or IL-1 on the maximal insulin secretory response of islets to glucose. Insulin secretion was not potentiated in perfused pancreases obtained from rats only 30 min after treatment with endotoxin. These results suggest that in vivo treatment with either endotoxin or IL-1 potentiates insulin secretion by increasing islet sensitivity to glucose. In addition, because endotoxin is known to potently stimulate the production and secretion of IL-1 in vivo, the results lend support to the hypothesis that the effects of endotoxin on insulin secretion may be mediated partially by IL-1.

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.

Hyperglycemic athymic nude mice: factors affecting in vitro insulin secretion

1992 ◽  
Vol 263 (6) ◽  
pp. E1131-E1133
Author(s):  
A. Zeidler ◽  
P. Edwards ◽  
J. Goldman ◽  
S. Kort ◽  
W. P. Meehan ◽  
...  
Keyword(s):  
Animal Model ◽  
Insulin Secretion ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Factors Affecting ◽  
In Vitro Insulin Secretion ◽  
Insulin Secretion In Vitro ◽  
And Control

The strain of athymic nude male mice (ANM) developed at the University of Southern California (USC) exhibits spontaneous hyperglycemia and relative hypoinsulinemia in vivo. To investigate factors that influence insulin secretion in this animal model of non-insulin-dependent diabetes mellitus, we utilized the isolated perfused mouse pancreas of the ANM-USC and control BALB/c mice. We compared in vitro glucose-induced insulin secretion in ANM-USC and control mice, inhibition of secretion by somatostatin, and variability of insulin secretion over the two-year period it took to complete these experiments. Glucose-induced insulin secretion from the isolated pancreas was biphasic in both ANM-USC and controls. Insulin secretion was quantitatively equal to or greater than control mice, depending on the phase of secretion analyzed and the source of the control mice. In contrast to pancreases of control mice, insulin secretion from ANM-USC pancreases was relatively resistant to inhibition of insulin secretion by somatostatin. Variability in insulin secretion over the two years in which these experiments were performed was greater from pancreases of control than that observed from pancreases of the ANM-USC. The hyperglycemic ANM-USC mouse does not demonstrate diminished insulin secretion in vitro yet is relatively hypoinsulinemic in vivo. Thus circulating factors other than somatostatin might contribute to the insulinopenic stage in this animal model.

Islet glucan-1,4-α-glucosidase: differential influence on insulin secretion induced by glucose and isobutylmethylxanthine in mice

1993 ◽  
Vol 138 (3) ◽  
pp. 391-400 ◽  
Author(s):  
A. Salehi ◽  
I. Lundquist
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Marked Reduction ◽  
Insulin Response ◽  
Indirect Evidence ◽  
Secretory Response ◽  
Isolated Pancreatic Islets ◽  
Enzyme Replacement ◽  
Insulin Secretory Response

ABSTRACT In previous in-vivo studies we have presented indirect evidence for the involvement of islet acid glucan-1,4-α-glucosidase (acid amyloglucosidase), a lysosomal glycogen-hydrolysing enzyme, in certain insulin secretory processes. In the present combined in-vitro and in-vivo investigation, we studied whether differential changes in islet acid amyloglucosidase activity were related to the insulin secretory response induced by two mechanistically different secretagogues, glucose and isobutylmethylxanthine (IBMX). It was observed that addition of the selective α-glucosidehydrolase inhibitor emiglitate (1 mmol/l) to isolated pancreatic islets resulted in a marked reduction of glucose-induced insulin release. This was accompanied by a pronounced suppression of islet activities of acid amyloglucosidase and acid α-glucosidase, whereas other lysosomal enzyme activities, such as acid phosphatase and N-acetyl-β-d-glucosaminidase, were unaffected. Furthermore, islets first incubated with emiglitate in the presence of high (16·7 mmol/l) glucose released less insulin than untreated controls in response to glucose in a second incubation period in the absence of emiglitate. In contrast, IBMX-induced insulin release was not influenced by emiglitate although accompanied by a marked reduction of islet activities of all three α-glucosidehydrolases. Basal insulin secretion (1 mmol glucose/1) was unaffected in the presence of emiglitate. In-vivo pretreatment of mice with highly purified fungal amyloglucosidase ('enzyme replacement'), a procedure known to increase islet amyloglucosidase activity, resulted in a greatly enhanced insulin secretory response to an i.v. glucose load. The increase in insulin release was accompanied by a markedly improved glucose tolerance curve in these animals. In contrast, enzyme pretreatment did not influence the insulin response or the blood glucose levels after an i.v. injection of IBMX. The data lend further support to our hypothesis that islet acid amyloglucosidase is involved in the multifactorial insulin secretory processes induced by glucose but not in those involving direct activation of the cyclic AMP system. The results also indicate separate, or at least partially separate, pathways for insulin release induced by glucose and IBMX. Journal of Endocrinology (1993) 138, 391–400

scholarly journals Nutrient Responsive Nesfatin-1 Regulates Energy Balance and Induces Glucose-Stimulated Insulin Secretion in Rats

Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3628-3637 ◽  
Author(s):  
R. Gonzalez ◽  
R. L. S. Perry ◽  
X. Gao ◽  
M. P. Gaidhu ◽  
R. G. Tsushima ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Secretion ◽  
Glucose Uptake ◽  
Pancreatic Islets ◽  
Whole Body ◽  
Isolated Pancreatic Islets ◽  
Brown Adipose ◽  
Glucose Stimulated Insulin Secretion ◽  
Body Energy

Nesfatin-1 is a recently discovered anorexigen, and we first reported nesfatin-like immunoreactivity in the pancreatic β-cells. The aim of this study was to characterize the effects of nesfatin-1 on whole-body energy homeostasis, insulin secretion, and glycemia. The in vivo effects of continuous peripheral delivery of nesfatin-1 using osmotic minipumps on food intake and substrate partitioning were examined in ad libitum-fed male Fischer 344 rats. The effects of nesfatin-1 on glucose-stimulated insulin secretion (GSIS) were examined in isolated pancreatic islets. L6 skeletal muscle cells and isolated rat adipocytes were used to assess the effects of nesfatin-1 on basal and insulin-mediated glucose uptake as well as on major steps of insulin signaling in these cells. Nesfatin-1 reduced cumulative food intake and increased spontaneous physical activity, whole-body fat oxidation, and carnitine palmitoyltransferase I mRNA expression in brown adipose tissue but did not affect uncoupling protein 1 mRNA in the brown adipose tissue. Nesfatin-1 significantly enhanced GSIS in vivo during an oral glucose tolerance test and improved insulin sensitivity. Although insulin-stimulated glucose uptake in L6 muscle cells was inhibited by nesfatin-1 pretreatment, basal and insulin-induced glucose uptake in adipocytes from nesfatin-1-treated rats was significantly increased. In agreement with our in vivo results, nesfatin-1 enhanced GSIS from isolated pancreatic islets at both normal (5.6 mm) and high (16.7 mm), but not at low (2 mm), glucose concentrations. Furthermore, nesfatin-1/nucleobindin 2 release from rat pancreatic islets was stimulated by glucose. Collectively, our data indicate that glucose-responsive nesfatin-1 regulates insulin secretion, glucose homeostasis, and whole-body energy balance in rats.

Decreased nutrient-stimulated insulin secretion in chronically hypoglycemic late-gestation fetal sheep is due to an intrinsic islet defect

2006 ◽  
Vol 291 (2) ◽  
pp. E404-E411 ◽  
Author(s):  
Paul J. Rozance ◽  
Sean W. Limesand ◽  
William W. Hay
Keyword(s):  
Insulin Secretion ◽  
Late Gestation ◽  
Human Infants ◽  
Fetal Sheep ◽  
Isolated Pancreatic Islets ◽  
Acute Hypoglycemia ◽  
Arterial Plasma ◽  
Glucose Stimulated Insulin Secretion

We measured in vivo and in vitro nutrient-stimulated insulin secretion in late gestation fetal sheep to determine whether an intrinsic islet defect is responsible for decreased glucose-stimulated insulin secretion (GSIS) in response to chronic hypoglycemia. Control fetuses responded to both leucine and lysine infusions with increased arterial plasma insulin concentrations (average increase: 0.13 ± 0.05 ng/ml leucine; 0.99 ± 0.26 ng/ml lysine). In vivo lysine-stimulated insulin secretion was decreased by chronic (0.37 ± 0.18 ng/ml) and acute (0.27 ± 0.19 ng/ml) hypoglycemia. Leucine did not stimulate insulin secretion following acute hypoglycemia but was preserved with chronic hypoglycemia (0.12 ± 0.09 ng/ml). Isolated pancreatic islets from chronically hypoglycemic fetuses had normal insulin and DNA content but decreased fractional insulin release when stimulated with glucose, leucine, arginine, or lysine. Isolated islets from control fetuses responded to all nutrients. Therefore, chronic late gestation hypoglycemia causes defective in vitro nutrient-regulated insulin secretion that is at least partly responsible for diminished in vivo GSIS. Chronic hypoglycemia is a feature of human intrauterine growth restriction (IUGR) and might lead to an islet defect that is responsible for the decreased insulin secretion patterns seen in human IUGR fetuses and low-birth-weight human infants.

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.

Inhibition by rat diazepam-binding inhibitor/acyl-CoA-binding protein of glucose-induced insulin secretion in the rat

1994 ◽  
Vol 131 (2) ◽  
pp. 201-204 ◽  
Author(s):  
Claes-Göran Östenson ◽  
Bo Ahrén ◽  
Sven Karlsson ◽  
Jens Knudsen ◽  
Suad Efendic
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Binding Protein ◽  
Insulin Response ◽  
Isolated Islets ◽  
High Concentration ◽  
Isolated Pancreatic Islets ◽  
Rat Pancreas

Östenson C-G, Ahrén B, Karlsson S, Knudsen J, Efendic S. Inhibition by rat diazepam-binding inhibitor/ acyl-CoA-binding protein of glucose-induced insulin secretion in the rat. Eur J Endocrinol 1994;131:201–4. ISSN 0804–4643 Diazepam-binding inhibitor (DBI) has been localized immunohistochemically in many organs. In porcine and rat pancreas, DBI is present in non-B-cells of the pancreatic islets. Porcine peptide also has been shown to suppress insulin secretion from rat pancreas in vitro. Recently, acyl-CoA-binding protein (ACBP) was isolated from rat liver and shown to be identical structurally to DBI isolated from rat brain. Using this rat DBI/ACBP, we have studied its effects on glucose-stimulated insulin secretion in the rat, both in vivo and in isolated pancreatic islets. Infusion iv of rDBI/ACBP (25 pmol/min) during glucose stimulation induced a moderate and transient reduction of plasma insulin levels. Moreover, rDBI/ACBP suppressed insulin release from batch-incubated isolated islets, stimulated by 16.7 mmol/l glucose, by 24% at 10 nmol/l (p < 0.05) and by 40% at 100 nmol/l (p < 0.01). The peptide (100 nmol/l) also inhibited the insulin response to glucose (16.7 mmol/l) from perifused rat islets by 31% (p < 0.05), mainly by affecting the acute-phase response. Finally, incubation of isolated islets in the presence of rDBI/ACBP antiserum (diluted 1:100 and 1:300) augmented the insulin response to 16.7 mmol/l glucose (p < 0.05 or even less). We conclude that rDBI/ACBP, administered iv or added to the incubation media, suppresses insulin secretion in the rat but that the effect is moderate despite the high concentration used. It is therefore unlikely that the peptide modulates islet hormone release, acting as a classical hormone via the circulation. However, the occurrence of DBI/ACBP in the islets and the enhancing effect by the rDBI/ACBP antibodies on glucose-stimulated insulin release suggest that the peptide is a local modulator of insulin secretion. C-G Östenson, Department of Endocrinology, Karolinska Hospital, S-171 76 Stockholm, Sweden

Sign in / Sign up

Export Citation Format

Share Document