scholarly journals Metabolic Disturbances and Defects in Insulin Secretion in Rats With Streptozotocin-Nicotinamide-Induced Diabetes

2013 ◽  
pp. 663-670 ◽  
Author(s):  
T. SZKUDELSKI ◽  
A. ZYWERT ◽  
K. SZKUDELSKA
Keyword(s):  
Body Weight ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Animal Studies ◽  
Diabetic Rats ◽  
Significant Rise ◽  
Metabolic Disturbances ◽  
Mild Diabetes ◽  
Insulin Secretory Response

Rats with diabetes induced by streptozotocin (STZ) and nicotinamide (NA) are often used in animal studies concerning various aspects of diabetes. In this experimental model, the severity of diabetes is different depending on doses of STZ and NA. Moreover, diabetic changes in rats with STZ-NA-induced diabetes are not fully characterized. In our present study, metabolic changes and insulin secretion were investigated in rats with diabetes induced by administration of 60 mg of STZ and 90 mg of NA per kg body weight. Four to six weeks after diabetes induction, insulin, glucagon and some metabolic parameters were determined to evaluate the severity of diabetes. Moreover, insulin secretory capacity of pancreatic islets isolated from control and diabetic rats was compared. It was demonstrated that administration of 60 mg of STZ and 90 mg of NA per kg body weight induced relatively mild diabetes, since insulin, glucagon and other analyzed parameters were only slightly affected in diabetic rats compared with control animals. In vitro studies revealed that insulin secretory response was preserved in pancreatic islets of diabetic rats, however, was lower than in islets of control animals. This effect was observed in the presence of different stimuli. Insulin secretion induced by 6.7 and 16.7 mmol/l glucose was moderately reduced in islets of diabetic rats compared with control islets. In the presence of leucine with glutamine, insulin secretion appeared to be also decreased in islets of rats with STZ-NA-induced diabetes. Insulinotropic action of 6.7 mmol/l glucose with forskolin was also deteriorated in diabetic islets. Moreover, it was demonstrated that at a non-stimulatory glucose, pharmacological depolarization of plasma membrane with a concomitant activation of protein kinase C evoked significant rise in insulin release in islets of control and diabetic rats. However, in diabetic islets, this effect was attenuated. These results indicate that impairment in insulin secretion in pancreatic islets of rats with mild diabetes induced by STZ and NA results from both metabolic and nonmetabolic disturbances in these islets.

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.

Intraportal transplantation of pancreatic islets into livers of diabetic rats. Reinnervation of islets and regulation of insulin secretion by the hepatic sympathetic nerves

Diabetes ◽  
1994 ◽  
Vol 43 (11) ◽  
pp. 1345-1352 ◽  
Author(s):  
A. Gardemann ◽  
K. Jungermann ◽  
V. Grosse ◽  
L. Cossel ◽  
F. Wohlrab ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Sympathetic Nerves ◽  
Diabetic Rats

Direct effect of parathyroid hormone on insulin secretion from pancreatic islets

1990 ◽  
Vol 258 (6) ◽  
pp. E975-E984 ◽  
Author(s):  
G. Z. Fadda ◽  
M. Akmal ◽  
L. G. Lipson ◽  
S. G. Massry
Keyword(s):  
Insulin Secretion ◽  
Parathyroid Hormone ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Direct Effect ◽  
Indirect Evidence ◽  
Cytosolic Calcium ◽  
Dependent Manner ◽  
Stimulation Of

Indirect evidence indicates that parathyroid hormone (PTH) interacts with pancreatic islets and modulates their insulin secretion. This property of PTH has been implicated in the genesis of impaired insulin release in chronic renal failure. We examined the direct effect of PTH-(1-84) and PTH-(1-34) on insulin release using in vitro static incubation and dynamic perifusion of pancreatic islets from normal rats. Both moieties of the hormone stimulated in a dose-dependent manner glucose-induced insulin release but higher doses inhibited glucose-induced insulin release. This action of PTH was modulated by the calcium concentration in the media. The stimulatory effect of PTH was abolished by its inactivation and blocked by its antagonist [Tyr-34]bPTH-(7-34)NH2. PTH also augmented phorbol ester (TPA)-induced insulin release, stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation by pancreatic islets, and significantly increased (+50 +/- 2.7%, P less than 0.01) their cytosolic calcium. Verapamil inhibited the stimulatory effect of PTH on insulin release. The data show that 1) pancreatic islets are a PTH target and may have PTH receptors, 2) stimulation of glucose-induced insulin release by PTH is mediated by a rise in cytosolic calcium, 3) stimulation of cAMP production by PTH and a potential indirect activation of protein kinase C by PTH may also contribute to the stimulatory effect on glucose-induced insulin release, and 4) this action of PTH requires calcium in incubation or perifusion media.

scholarly journals Regulation of glucokinase in pancreatic islets by prolactin: a mechanism for increasing glucose-stimulated insulin secretion during pregnancy

2007 ◽  
Vol 193 (3) ◽  
pp. 367-381 ◽  
Author(s):  
Anthony J Weinhaus ◽  
Laurence E Stout ◽  
Nicholas V Bhagroo ◽  
T Clark Brelje ◽  
Robert L Sorenson
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Glucose Transporter ◽  
Β Cells ◽  
Glucose Transporter 2 ◽  
Underlying Mechanisms ◽  
Glucose Stimulated Insulin Secretion ◽  
Induced Changes

Glucokinase activity is increased in pancreatic islets during pregnancy and in vitro by prolactin (PRL). The underlying mechanisms that lead to increased glucokinase have not been resolved. Since glucose itself regulates glucokinase activity in β-cells, it was unclear whether the lactogen effects are direct or occur through changes in glucose metabolism. To clarify the roles of glucose metabolism in this process, we examined the interactions between glucose and PRL on glucose metabolism, insulin secretion, and glucokinase expression in insulin 1 (INS-1) cells and rat islets. Although the PRL-induced changes were more pronounced after culture at higher glucose concentrations, an increase in glucose metabolism, insulin secretion, and glucokinase expression occurred even in the absence of glucose. The presence of comparable levels of insulin secretion at similar rates of glucose metabolism from both control and PRL-treated INS-1 cells suggests the PRL-induced increase in glucose metabolism is responsible for the increase in insulin secretion. Similarly, increases in other known PRL responsive genes (e.g. the PRL receptor, glucose transporter-2, and insulin) were also detected after culture without glucose. We show that the upstream glucokinase promoter contains multiple STAT5 binding sequences with increased binding in response to PRL. Corresponding increases in glucokinase mRNA and protein synthesis were also detected. This suggests the PRL-induced increase in glucokinase mRNA and its translation are sufficient to account for the elevated glucokinase activity in β-cells with lactogens. Importantly, the increase in islet glucokinase observed with PRL is in line with that observed in islets during pregnancy.

Phytochemical Screening and Anti-Diabetic Efficacy of O. Sanctum Seed Extract on Streptozotocin Induced Diabetic Rats

2017 ◽  
Vol 54 (3) ◽  
pp. 336
Author(s):  
Kavitha K. ◽  
Ponne S.
Keyword(s):  
Body Weight ◽  
Digestive Enzymes ◽  
Fasting Blood Glucose ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Seed Extract ◽  
Phytochemical Screening ◽  
Weight Changes

The present study was designed to assess the in vitro and in vivo anti-diabetic efficacy of <em>O. sanctum</em> seed and its phytochemical screening. In vitro inhibitory effect on carbohydrate digestive enzymes like α-amylase and α-glucosidase and in vivo parameters such as fasting blood glucose and body weight changes were studied, a potent inhibitory effect was observed on activities of digestive enzymes and a marked decrease in the glucose level in the <em>O. sanctum</em> seed extract treated streptozotocin induced diabetic rats was noted. Further a marked reduction in body weight was also observed.

THYROXINE METABOLISM IN DIABETIC RATS

1977 ◽  
Vol 86 (2) ◽  
pp. 336-343 ◽  
Author(s):  
A. A. Zaninovich ◽  
T. J. Brown ◽  
R. Boado ◽  
N. R. Bromage ◽  
A. J. Matty
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Least Squares Method ◽  
Intraperitoneal Administration ◽  
Binding Activity ◽  
Diabetic Rats ◽  
Control Group ◽  
Metabolic Clearance ◽  
Distribution Space

ABSTRACT The metabolism of thyroxine (T4) was determined in untreated and in insulin-treated diabetic rats. The results were compared with those obtained in a control group. Male Wistar rats weighing approximately 200 g were made diabetic by the intraperitoneal administration of streptozotocin (6.5 mg/100 g body weight) and 17 of those with blood sugar levels above 500 mg/100 ml were studied. In addition, 11 insulin-treated diabetic and 18 control rats were investigated. All the animals were injected intravenously with a tracer dose of [125I]T4 (1 μCi and 0.015 μg). After this blood samples were obtained by cardiac puncture at 16, 24, 40 and 48 h. The 24-h urinary excretion of inorganic 125iodide was also determined. The parameters of T4 metabolism were obtained by the least squares method and by an extrapolation technique. In untreated diabetic rats the fractional T4 turnover was 4.4%h, the distribution space 36.7 ml/100 g body weight, metabolic clearance 1.57 ml/100 g/h and urinary clearance 0.33 ml/100 g/h. The 24-h urinary excretion of 125iodide was 21.3 % of the injected radioactivity. Of these values the distribution space (P < 0.001) and metabolic clearance (P < 0.05) were significantly increased above those in the control animals. In insulin-treated rats all parameters were within normal values. Among these groups the serum T4 concentration was measured in 6 control, 5 untreated diabetic and 6 insulin-treated animals. The untreated diabetic animals had a significantly decreased serum T4 level but this was balanced by an enlarged distribution space so that the final hormone degradation was normal. In addition, the T4 binding activity of serum was assessed by the in vitro red cells uptake of [125I] T4 and by determining the proportion of serum free T4. Both these indices indicated a decrease in serum binding activity in the diabetic animals. The data suggest that the fall in serum T4 levels observed in the untreated diabetic rats was the result of decreased plasma binding of T4 and an increase in distribution space precipitated by lack of insulin.

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.

RES hyperphagocytosis by rats with streptozotocin-induced diabetes mellitus

1981 ◽  
Vol 240 (3) ◽  
pp. G225-G231
Author(s):  
R. P. Cornell
Keyword(s):  
Body Weight ◽  
Insulin Dose ◽  
Reticuloendothelial System ◽  
Diabetic Rats ◽  
Phagocytic Index ◽  
Control Value ◽  
Colloidal Carbon ◽  
Significant Difference

In contrast to previous studies of neutrophils from diabetic animals and humans in vitro and of macrophages from diabetic humans in vivo, which reported phagocytic depression, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon was observed in rats at 14 and 28 days after diabetes induction with streptozotocin (STZ). Carbon clearance half times were significantly enhanced to 6.3 +/- 0.79 and 8.1 +/- 1.04 min at 14 and 28 days post-STZ, respectively, compared with the nondiabetic value (12.7 +/- 0.98 min). The severity of uncontrolled STZ-induced diabetes in rats was confirmed by significant hypoinsulinemia, hyperglucagonemia, hyperglycemia, and hyperlipidemia. Although body weights of STZ-diabetic animals declined progressively, liver weights as a percent of body weight increased above the control value at 14 and 28 days post-STZ. In fact, expression of carbon phagocytosis as the corrected phagocytic index, which accounts for changes in liver and spleen weights relative to body weight, eliminated the significant difference between STZ-diabetic and nondiabetic animals. Antibiotic treatment of diabetic rats failed to alter the hyperphagocytosis, implying that a chronic bacterial infection was not the cause of phagocytic stimulation. Daily insulin replacements, but not a single large insulin dose to 14-day post-STZ rats, reversed the enhanced phagocytosis of colloidal carbon.

Chronic exercise enhances insulin secretion ability of pancreatic islets without change in insulin content in non-diabetic rats

2013 ◽  
Vol 430 (2) ◽  
pp. 676-682 ◽  
Author(s):  
Miho Tsuchiya ◽  
Yasuko Manabe ◽  
Kenichiro Yamada ◽  
Yasuro Furuichi ◽  
Masahiro Hosaka ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Diabetic Rats ◽  
Insulin Content ◽  
Chronic Exercise

scholarly journals Insulinotropic and β-cell protective action of cuminaldehyde, cuminol and an inhibitor isolated from Cuminum cyminum in streptozotocin-induced diabetic rats

2013 ◽  
Vol 110 (8) ◽  
pp. 1434-1443 ◽  
Author(s):  
Swapnil B. Patil ◽  
Shreehari S. Takalikar ◽  
Madhav M. Joglekar ◽  
Vivek S. Haldavnekar ◽  
Akalpita U. Arvindekar
Keyword(s):  
Insulin Secretion ◽  
Protective Action ◽  
Diabetic Rats ◽  
Probable Mechanism ◽  
Bioactive Components ◽  
Β Cell ◽  
Cuminum Cyminum ◽  
Insulin Secretagogue ◽  
Ether Fraction

Cuminum cyminum, a commonly used spice, is known to have anti-diabetic action. The present study aims towards the isolation of bioactive components from C. cyminum and the evaluation of their insulin secretagogue potential with the probable mechanism and β-cell protective action. The anti-diabetic activity was detected in the petroleum ether (pet ether) fraction of the C. cyminum distillate and studied through in vivo and in vitro experiments. Bioactive components were identified through GC–MS, Fourier transform infrared spectroscopy and NMR analysis. The isolated components were evaluated for their insulin secretagogue action using rat pancreatic islets. Further, the probable mechanism of stimulation of islets was evaluated through in vitro studies using diazoxide, nifedipine and 3-isobutyl-1-methylxanthine. β-Cell protection was evaluated using the (1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan) (MTT) assay, the alkaline comet assay and nitrite production. The administration of the pet ether fraction for 45 d to streptozotocin-induced diabetic rats revealed an improved lipid profile. Cuminaldehyde and cuminol were identified as potent insulinotrophic components. Cuminaldehyde and cuminol (25 μg/ml) showed 3·34- and 3·85-fold increased insulin secretion, respectively, than the 11·8 mm-glucose control. The insulinotrophic action of both components was glucose-dependent and due to the closure of the ATP-sensitive K (K+-ATP) channel and the increase in intracellular Ca2+ concentration. An inhibitor of insulin secretion with potent β-cell protective action was also isolated from the same pet ether fraction. In conclusion, C. cyminum was able to lower blood glucose without causing hypoglycaemia or β-cell burn out. Hence, the commonly used spice, C. cyminum, has the potential to be used as a novel insulinotrophic therapy for prolonged treatment of diabetes.

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