Insulin feedback actions: complex effects involving isoforms of islet nitric oxide synthase

Regulatory Peptides
Javier Jimenez-FeltstromAlbert Salehi

Abstract

The present study examined the effects of exogenous insulin on C-peptide release in relation to islet activities of neural constitutive nitric oxide synthase (ncNOS) and inducible NOS (iNOS). The dose-response curves for glucose-stimulated insulin and C-peptide release from isolated islets were practically identical: 0.05-0.1 nmol/l insulin stimulated, 1-100 nmol/l had no effect, whereas concentrations >/=250 nmol/l ("high insulin"), inhibited C-peptide release. Both the stimulatory and inhibitory effects were abolished by the phosphatidylinositol 3'-kinase inhibitor wortmannin. Addition of a NOS inhibitor partially reversed the inhibitory action of high insulin, but had no effect on the stimulatory action of low insulin (0.1 nmol/l). Moreover, high insulin markedly increased islet ncNOS activity and induced a strong iNOS activity. As shown biochemically and with confocal microscopy, the stimulatory action of high insulin on NOS activities and the associated inhibition of C-peptide release were reversed by raising cyclic AMP through addition of either glucagon-like peptide 1 (GLP-1) or dibutyryl cyclic AMP (Bt(2)cAMP) to the incubated islets. We conclude that the positive feedback mechanisms of action of insulin are independent...Continue Reading

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Citations

Jan 19, 2008·Endocrinology·Jennifer L BeithJames D Johnson
Sep 10, 2014·Diabetes, Obesity & Metabolism·E Gylfe, A Tengholm
Apr 14, 2016·Molecular Metabolism·Simone Hausmann, Siegfried Ussar
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Sep 7, 2012·Diabetes, Obesity & Metabolism·M BraunP Rorsman
Dec 23, 2014·Basic & Clinical Pharmacology & Toxicology·Anne Wuttke
Aug 16, 2005·Molecular and Cellular Endocrinology·Dan S Luciani, James D Johnson
Jul 7, 2015·Journal of Basic and Clinical Physiology and Pharmacology·Prabhakaran Prabha PreethaThankappan Rajamohan
May 17, 2008·Annual Review of Nutrition·Ingo B LeibigerPer-Olof Berggren
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Aug 24, 2019·Frontiers in Physiology·Maria L MizgierJose E Galgani
Mar 11, 2020·International Journal of Molecular Sciences·Nadia Rachdaoui
Mar 5, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Xiaozhuo ChenAili Guo
Oct 15, 2019·Biochemical and Biophysical Research Communications·Israa Mohammed Al-AmilyAlbert Salehi

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