scholarly journals Ghrelin activates neuronal constitutive nitric oxide synthase in pancreatic islet cells while inhibiting insulin release and stimulating glucagon release

2005 ◽  
Vol 128 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Saleem S. Qader ◽  
Ingmar Lundquist ◽  
Mats Ekelund ◽  
Rolf Håkanson ◽  
Albert Salehi
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Insulin Release ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Glucagon Release ◽  
Pancreatic Islet Cells ◽  
Constitutive Nitric Oxide Synthase ◽  
Oxide Synthase

Islet constitutive nitric oxide synthase: biochemical determination and regulatory function

1996 ◽  
Vol 270 (6) ◽  
pp. C1634-C1641 ◽  
Author(s):  
A. Salehi ◽  
M. Carlberg ◽  
R. Henningson ◽  
I. Lundquist
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Insulin Release ◽  
Glucagon Secretion ◽  
Isolated Islets ◽  
Regulatory Function ◽  
No Production ◽  
Glucagon Release ◽  
Constitutive Nitric Oxide Synthase ◽  
Oxide Synthase

Recent immunohistochemical findings suggested that a constitutive nitric oxide synthase (cNOS) resides in endocrine pancreas. Here we provide direct biochemical evidence for the presence of cNOS activity in isolated islets. The regulating influence of this nitric oxide synthase (NOS) activity for islet hormone release was also investigated. We observed that cNOS activity could be quantitated in islet homogenates by monitoring the formation of L-citrulline from L-arginine using an Amprep CBA cation-exhange minicolumn before derivatization with o-phthaldialdehyde and subsequent high-performance liquid chromatography analysis. The islet NOS was dependent on both Ca2+ and calmodulin and suppressed by the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME). This effect was enantiomerically specific. Islet insulin release induced by a mixture of L-arginine and glucose was enhanced by L-NAME, whereas L-arginine-induced glucagon release was inhibited. The effect of L-NAME on insulin release was dose dependently potentiated by increasing glucose concentrations, suggesting that glucose is an important regulator of islet NO production. Complementary in vivo studies showed similar results, i.e., the insulin secretory response to a mixture of glucose and L-arginine was extremely enhanced by pretreatment with L-NAME, whereas L-arginine-stimulated glucagon response was suppressed. Finally, in isolated islets, the intracellular nitric oxide (NO) donor hydroxylamine suppressed insulin release and increased glucagon release. In summary, the islets of Langerhans contain a constitutive, Ca2+/calmodulin-dependent isoform of NOS. Islet NO suppressed insulin but enhanced glucagon secretion. The data also suggest a negative feedback by NO on glucose-induced insulin release. The islet NO system is a novel and important regulatory factor in insulin and glucagon secretion.

Role of nitric oxide synthase isoforms in glucose-stimulated insulin release

2002 ◽  
Vol 283 (1) ◽  
pp. C296-C304 ◽  
Author(s):  
Ragnar Henningsson ◽  
Albert Salehi ◽  
Ingmar Lundquist
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Insulin Release ◽  
Type Ii Diabetes Mellitus ◽  
No Production ◽  
No Donor ◽  
Nos Inhibitors ◽  
Constitutive Nitric Oxide Synthase ◽  
Oxide Synthase

The role of islet constitutive nitric oxide synthase (cNOS) in insulin-releasing mechanisms is controversial. By measuring enzyme activities and protein expression of NOS isoforms [i.e., cNOS and inducible NOS (iNOS)] in islets of Langerhans cells in relation to insulin secretion, we show that glucose dose-dependently stimulates islet activities of both cNOS and iNOS, that cNOS-derived nitric oxide (NO) strongly inhibits glucose-stimulated insulin release, and that short-term hyperglycemia in mice induces islet iNOS activity. Moreover, addition of NO gas or an NO donor inhibited glucose-stimulated insulin release, and different NOS inhibitors effected a potentiation. These effects were evident also in K+-depolarized islets in the presence of the ATP-sensitive K+ channel opener diazoxide. Furthermore, our results emphasize the necessity of measuring islet NOS activity when using NOS inhibitors, because certain concentrations of certain NOS inhibitors might unexpectedly stimulate islet NO production. This is shown by the observation that 0.5 mmol/l of the NOS inhibitor N G-monomethyl-l-arginine (l-NMMA) stimulated cNOS activity in parallel with an inhibition of the first phase of glucose-stimulated insulin release in perifused rats islets, whereas 5.0 mmol/l of l-NMMA markedly suppressed cNOS activity concomitant with a great potentiation of the insulin secretory response. The data strongly suggest, but do not definitely prove, that glucose indeed has the ability to stimulate both cNOS and iNOS in the islets and that NO might serve as a negative feedback inhibitor of glucose-stimulated insulin release. The results also suggest that hyperglycemia-evoked islet NOS activity might be one of multiple factors involved in the impairment of glucose-stimulated insulin release in type II diabetes mellitus.

Evaluation of the long-term pancreatic effects of constitutive nitric oxide synthase inhibition in dogs

2004 ◽  
Vol 12 (1) ◽  
pp. 33-45 ◽  
Author(s):  
K. L. Kolaja ◽  
R. R. Bell ◽  
D. Janssen ◽  
P. T. Manning ◽  
M. J. Schlosser ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Constitutive Nitric Oxide Synthase ◽  
Oxide Synthase

A constitutive nitric oxide synthase modulates insulin secretion in the INS-1 cell line

2001 ◽  
Vol 183 (1-2) ◽  
pp. 41-48 ◽  
Author(s):  
P Beffy ◽  
A.D Lajoix ◽  
P Masiello ◽  
S Dietz ◽  
S Péraldi-Roux ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Secretion ◽  
Nitric Oxide Synthase ◽  
Cell Line ◽  
Constitutive Nitric Oxide Synthase ◽  
Oxide Synthase
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