scholarly journals Palmitic acid increase levels of pancreatic duodenal homeobox-1 and p38/stress-activated protein kinase in islets from rats maintained on a low protein diet

2006 ◽  
Vol 96 (6) ◽  
pp. 1006-1012 ◽  
Author(s):  
Vanessa C. Arantes ◽  
Marise A. B. Reis ◽  
Márcia Q. Latorraca ◽  
Fabiano Ferreira ◽  
Luiz Fabrízio Stoppiglia ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Palmitic Acid ◽  
Insulin Release ◽  
Culture Medium ◽  
Cell Physiology ◽  
Low Protein ◽  
Severe Reduction ◽  
Insulin Mrna ◽  
And Control

A severe reduction in insulin release in response to glucose is consistently noticed in protein-deprived rats and is attributed partly to the chronic exposure to elevated levels of NEFA. Since the pancreatic and duodenal transcription factor homeobox 1 (PDX-1) is important for the maintenance of β-cell physiology, and since PDX-1 expression is altered in the islets of rats fed a low protein (LP) diet and that rats show high NEFA levels, we assessed PDX-1 and insulin mRNA expression, as well as PDX-1 and p38/stress activated protein kinase 2 (SAPK2) protein expression, in islets from young rats fed low (6 %) or normal (17 %; control) protein diets and maintained for 48 h in culture medium containing 5·6 mmol/l glucose, with or without 0·6 mmol/l palmitic acid. We also measured glucose-induced insulin secretion and glucose metabolism. Insulin secretion by isolated islets in response to 16·7 mmol/l glucose was reduced in LP compared with control rats. In the presence of NEFA, there was an increase in insulin secretion in both groups. At 2·8 mmol/l glucose, the metabolism of this sugar was reduced in LP islets, regardless of the presence of this fatty acid. However, when challenged with 16·7 mmol/l glucose, LP and control islets showed a severe reduction in glucose oxidation in the presence of NEFA. The PDX-1 and insulin mRNA were significantly higher when NEFA was added to the culture medium in both groups of islets. The effect of palmitic acid on PDX-1 and p38/SAPK2 protein levels was similar in LP and control islets, but the increase was much more evident in LP islets. These results demonstrate the complex interrelationship between nutrients in the control of insulin release and support the view that fatty acids play an important role in glucose homeostasis by affecting molecular mechanisms and stimulus/secretion coupling pathways.

Nutritional recovery from a low-protein diet during pregnancy does not restore the kinetics of insulin secretion and Ca2+ or alterations in the cAMP/PKA and PLC/PKC pathways in islets from adult rats

2018 ◽  
Vol 43 (12) ◽  
pp. 1257-1267
Author(s):  
Leonardo Marin ◽  
Hellen Barbosa Faria Silva ◽  
Gabriela Damin ◽  
Letícia Martins Ignacio-Souza ◽  
Sílvia Regina de Lima Reis ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Insulin Release ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Second Phase ◽  
Adult Rats ◽  
Low Protein ◽  
Nutritional Recovery ◽  
Kinetics Of

We investigated the insulin release induced by glucose, the Ca2+ oscillatory pattern, and the cyclic AMP (cAMP)/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC) pathways in islets from adult rats that were reared under diets with 17% protein (C) or 6% protein (LP) during gestation, suckling, and after weaning and in rats receiving diets with 6% protein during gestation and 17% protein after birth (R). First-phase glucose-induced insulin secretion was reduced in LP and R islets, and the second phase was partially restored in the R group. Glucose stimulation did not modify intracellular Ca2+ concentration, but it reduced the Ca2+ oscillatory frequency in the R group compared with the C group. Intracellular cAMP concentration was higher and PKA-Cα expression was lower in the R and LP groups compared with the C group. The PKCα content in islets from R rats was lower than that in C and LP rats. Thus, nutritional recovery from a low-protein diet during fetal life did not repair the kinetics of insulin release, impaired Ca2+ handling, and altered the cAMP/PKA and PLC/PKC pathways.

Nitric oxide donor SIN-1 inhibits insulin release

1996 ◽  
Vol 271 (4) ◽  
pp. C1098-C1102 ◽  
Author(s):  
A. Sjoholm
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Kinase C ◽  
Stimulus Secretion Coupling

Preceding the onset of insulin-dependent diabetes mellitus, pancreatic islets are infiltrated by macrophages secreting interleukin-1 beta, which exerts cytotoxic and inhibitory actions on islet beta-cell insulin secretion through induction of nitric oxide (NO) synthesis. The influence of the NO donor 3-morpholinosydnonimine (SIN-1) on insulin secretion from isolated pancreatic islets in response to various secretagogues was investigated. Stimulation of insulin release evoked by glucose, phospholipase C activation with carbachol, and protein kinase C activation with phorbol ester were obtained by SIN-1, whereas the response to adenylyl cyclase activation or K(+)-induced depolarization was not affected. It is concluded that enzymes involved in glucose catabolism, phospholipase C or protein kinase C, may be targeted by NO. Reversal of SIN-1 inhibition of glucose-stimulated insulin release by dithiothreitol suggests that NO may inhibit insulin secretion partly by S-nitrosylation of thiol residues in key proteins in the stimulus-secretion coupling. These adverse effects of NO on the beta-cell stimulus-secretion coupling may be of importance for the development of the impaired insulin secretion characterizing diabetes mellitus.

scholarly journals Activation of protein kinase C partially alleviates noradrenaline inhibition of insulin secretion

1993 ◽  
Vol 289 (2) ◽  
pp. 497-501 ◽  
Author(s):  
S J Persaud ◽  
P M Jones ◽  
S L Howell
Keyword(s):  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Insulin Release ◽  
Inhibitory Effect ◽  
Kinase C ◽  
Dependent Protein ◽  
Glucose Stimulated Insulin Secretion ◽  
Rat Islets Of Langerhans

The sympathetic neurotransmitter noradrenaline (NA) fully inhibited both phases of glucose-stimulated insulin secretion from rat islets of Langerhans. The secretory response to the protein kinase C (PKC) activator, 4 beta-phorbol myristate acetate (4 beta PMA), in the absence of exogenous glucose was also abolished by NA. However, at 20 mM glucose 4 beta PMA partially alleviated the inhibitory effect of NA both on insulin release and on cyclic AMP generation. Inhibition of insulin release by NA, albeit much decreased, was still observed in the presence of maximal stimulatory concentrations of both 4 beta PMA and dibutyryl cyclic AMP. The relieving effect of 4 beta PMA on the inhibition of insulin secretion by NA was not overcome by the competitive antagonist of cyclic AMP-dependent protein kinase, Rp-adenosine 3′,5′-cyclic phosphorothioate. Down-regulation of islet PKC activity by overnight exposure to 4 beta PMA did not affect the inhibitory capacity of NA. These results suggest that NA inhibits insulin release independently of interaction with PKC, but that activation of this enzyme decreases the inhibitory effect of NA at stimulatory concentrations of glucose. This protective effect of 4 beta PMA could not be attributed to a decrease in NA inhibition of cyclic AMP generation.

scholarly journals Maternal Low Protein Isocaloric Diet Suppresses Pancreatic β-Cell Proliferation in Mouse Offspring via miR-15b

Endocrinology ◽  
2016 ◽  
Vol 157 (12) ◽  
pp. 4782-4793 ◽  
Author(s):  
Yutong Su ◽  
Xiuli Jiang ◽  
Yanli Li ◽  
Feng Li ◽  
Yulong Cheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
Islet Cells ◽  
Control Diet ◽  
Cell Mass ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Isocaloric Diet ◽  
Low Protein ◽  
And Control

The mechanism underlying the increased susceptibility of type 2 diabetes in offspring of maternal malnutrition is poorly determined. Here we tested the hypothesis that functional microRNAs (miRNAs) mediated the maternal low-protein (LP) isocaloric diet induced pancreatic β-cell impairment. We performed miRNA profiling in the islets from offspring of LP and control diet mothers to explore the potential functional miRNAs responsible for β-cell dysfunction. We found that LP offspring exhibited impaired glucose tolerance due to decreased β-cell mass and insulin secretion. Reduction in the β-cell proliferation rate and cell size contributed to the decreased β-cell mass. MiR-15b was up-regulated in the islets of LP offspring. The up-regulated miR-15b inhibited pancreatic β-cell proliferation via targeting cyclin D1 and cyclin D2. Inhibition of miR-15b in LP islet cells restored β-cell proliferation and insulin secretion. Our findings demonstrate that miR-15b is critical for the regulation of pancreatic β-cells in offspring of maternal protein restriction, which may provide a further insight for β-cell exhaustion originated from intrauterine growth restriction.

scholarly journals Microfluidic-enabled quantitative measurements of insulin release dynamics from single islets of Langerhans in response to 5-palmitic acid hydroxy stearic acid

Lab on a Chip ◽  
2018 ◽  
Vol 18 (18) ◽  
pp. 2873-2882 ◽  
Author(s):  
Basel Bandak ◽  
Lian Yi ◽  
Michael G. Roper
Keyword(s):  
Insulin Secretion ◽  
Stearic Acid ◽  
Palmitic Acid ◽  
Insulin Release ◽  
Islets Of Langerhans ◽  
Microfluidic Device ◽  
Hydroxy Stearic Acid ◽  
Quantitative Measurements

A microfluidic device was developed to investigate the effects of a potential anti-diabetic lipid on patterns 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

Stimulatory effects of taurine on insulin secretion by fetal rat islets cultured in vitro

1996 ◽  
Vol 151 (3) ◽  
pp. 501-506 ◽  
Author(s):  
H Cherif ◽  
B Reusens ◽  
S Dahri ◽  
C Remacle ◽  
J-J Hoet
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Ringer Solution ◽  
Sulfur Amino Acids ◽  
Camp Content ◽  
Rpmi Medium ◽  
Low Protein ◽  
Fetal Rat ◽  
Fetal Islets

Abstract Islets of rat fetuses born to mothers fed a low protein diet (LP) have a depressed insulin secretion in vitro in response to secretagogues. These fetuses have lower plasma levels of taurine than controls. The aim of this study was to analyze the effect of taurine on fetal islets insulin secretion. After 5 days of culture in serum containing standard RPMI medium, islets were cultured for 2 days in serum-free DME/F12 medium with 8·2 or 16·7 mm glucose alone or with taurine at 0·3 or 3 mm. They were then incubated for 120 min in Krebs Ringer solution with glucose alone (5·6 or 16·7 mm) or glucose (5·6 mm) added to leucine or arginine (both at 10 mm). In both concentrations of glucose, taurine increased the fractional insulin release by islets stimulated with secretagogues tested during the incubation. The effect did not seem to be mediated by changes in cAMP content. In a second set of experiments, islets cultured in RPMI medium for 7 days were incubated in the presence of Krebs Ringer solution with leucine (10 mm) or with sulfur amino acids (taurine at 10 mm, methionine or cysteine at 5 mm) for 120 min. Taurine and methionine stimulated insulin release at the same magnitude as leucine, whereas cysteine had no effect. In conclusion, taurine enhances insulin secretion by fetal islets, at least in vitro. Low taurine levels in fetuses from LP mothers might be implicated in their depressed insulin secretion. Journal of Endocrinology (1996) 151, 501–506

Resveratrol-induced inhibition of insulin secretion from rat pancreatic islets: evidence for pivotal role of metabolic disturbances

2007 ◽  
Vol 293 (4) ◽  
pp. E901-E907 ◽  
Author(s):  
Tomasz Szkudelski
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Calcium Channels ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Estrogenic Activity ◽  
Hormone Secretion ◽  
Lactate Production ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

Resveratrol is a stilbene present in different plant species and exerting numerous beneficial effects, including prevention of diabetes and attenuation of some diabetic complications. Its inhibitory effect on insulin secretion was recently documented, but the exact mechanism underlying this action remains unknown. Experiments employing diazoxide and a high concentration of K+revealed that, in depolarized pancreatic islets incubated for 90 min with resveratrol (1, 10, and 100 μM), insulin secretion stimulated by glucose and leucine was impaired. The attenuation of the insulin secretory response to 6.7 mM glucose was not abrogated by blockade of intracellular estrogen receptors and was found to be accompanied by diminished islet glucose oxidation, enhanced lactate production, and reduced ATP levels. Glucose-induced hyperpolarization of the mitochondrial membrane was also reduced in the presence of resveratrol. Moreover, in depolarized islets incubated with 2.8 mM glucose, activation of protein kinase C or protein kinase A potentiated insulin release; however, under these conditions, resveratrol was ineffective. Further studies also revealed that, under conditions of blocked voltage-dependent calcium channels, the stilbene reduced insulin secretion induced by a combination of glucose with forskolin. These data demonstrate that resveratrol 1) inhibits the amplifying pathway of insulin secretion, 2) exerts an insulin-suppressive effect independently of its estrogenic/anti-estrogenic activity, 3) shifts islet glucose metabolism from mitochondrial oxidation to anaerobic, 4) fails to abrogate insulin release promoted without metabolic events, and 5) does not suppress hormone secretion as a result of the direct inhibition of Ca2+influx through voltage-dependent calcium channels.

Acute and long-term effects of metformin on the function and insulin secretory responsiveness of clonal β-cells

2010 ◽  
Vol 391 (12) ◽  
Author(s):  
Joan M. McKiney ◽  
Nigel Irwin ◽  
Peter R. Flatt ◽  
Clifford J. Bailey ◽  
Neville H. McClenaghan
Keyword(s):  
Insulin Secretion ◽  
Cell Viability ◽  
Palmitic Acid ◽  
Insulin Release ◽  
Prolonged Exposure ◽  
Long Term Effects ◽  
Β Cell ◽  
Beneficial Effects ◽  
Intracellular Ca ◽  
Glucose Stimulated Insulin Secretion

Abstract Functional effects of acute and prolonged (48 h) exposure to the biguanide drug metformin were examined in the clonal pancreatic β-cell line, BRIN-BD11. Effects of metformin on prolonged exposure to excessive increased concentrations of glucose and palmitic acid were also assessed. In acute 20-min incubations, 12.5–50 μm metformin did not alter basal (1.1 mm glucose) or glucose-stimulated (16.7 mm glucose) insulin secretion. However, higher concentrations of metformin (100–1000 μm) increased (1.3–1.5-fold; p<0.001) insulin release at basal glucose concentrations, but had no effect on glucose-stimulated insulin secretion. There were no apparent acute effects of metformin on intracellular Ca2+ concentrations, but metformin enhanced (p<0.05 to p<0.01) the acute insulinotropic actions of GIP and GLP-1. Exposure for 48 h to 200 μm metformin improved aspects of β-cell insulin secretory function, whereas these benefits were lost at 1 mm metformin. Prolonged glucotoxic and lipotoxic conditions impaired β-cell viability and insulin release in response to glucose and to a broad range of insulin secretagogues. Concomitant culture with 200 μm metformin partially reversed many of the adverse effects of prolonged glucotoxic conditions. However, there were no beneficial effects of metformin under prolonged culture with elevated concentrations of palmitic acid. The results suggest that metformin exerts direct effects on β-cell viability, function and survival that could contribute to the use of this agent in the treatment of type 2 diabetes.

scholarly journals Decreased Cholinergic Stimulation of Insulin Secretion by Islets from Rats Fed a Low Protein Diet Is Associated with Reduced Protein Kinase Cα Expression

2003 ◽  
Vol 133 (3) ◽  
pp. 695-699 ◽  
Author(s):  
Fabiano Ferreira ◽  
Eliane Filiputti ◽  
Vanessa C. Arantes ◽  
Luis F. Stoppiglia ◽  
Eliana P. Araújo ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Cholinergic Stimulation ◽  
Low Protein ◽  
Protein Kinase Cα ◽  
Stimulation Of
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