Prolonged Plasma Half-Life of Insulin in Patients with a Genetic Defect of High Affinity Binding Sites

Dreyer, M.; Matthaei, S.; Kühnau, J; Rüdiger, H. W.

doi:10.1055/s-2007-1012285

Cited by 13 publications

(7 citation statements)

References 8 publications

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“…Both p38MAPK and ERK1\2 phosphorylation increased dose-dependently and reached maximal levels at 100 pM C-peptide. These effective concentrations of C-peptide are comparable with the K ass value (2.0-3.3 nM) obtained by an in itro binding study [2] and with circulating concentrations (100 pM-1 nM) of C-peptide in healthy subjects [27][28][29]. Thus, it might be that C-peptide fully interacts with its putative receptor(s) and activates the p38MAPK and ERK pathways under normal physiological conditions.…”

Section: Discussionsupporting

confidence: 83%

Proinsulin C-peptide activates cAMP response element-binding proteins through the p38 mitogen-activated protein kinase pathway in mouse lung capillary endothelial cells

Kitamura

Kimura

Jung

et al. 2002

Biochemical Journal

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Proinsulin C-peptide has been reported to have some biological activities and to be possibly involved in the development of diabetic microangiopathy. In the present study, we examined the effects of C-peptide on the mitogen-activated protein kinase pathway in LEII mouse lung capillary endothelial cells. Stimulation of the cells with C-peptide increased both p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated kinase (ERK1/2) activities and activity-related site-specific phosphorylation of the respective kinases in a concentration-dependent manner, but failed to activate c-Jun N-terminal kinase. Stimulation of the cells with C-peptide also induced site-specific phosphorylation of cAMP response element (CRE)-binding protein (CREB)/activating transcription factor 1 (ATF1), and thereby binding of these transcription factors to CRE. Among three CREB kinases tested, phosphorylation of mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) was induced after stimulation with C-peptide. The phosphorylation of CREB, ATF1 and MAPKAP-K2 were inhibited by SB203580, a p38MAPK inhibitor, but not by PD98059, an ERK kinase inhibitor. These results indicate that C-peptide activates p38MAPK followed by MAPKAP-K2 to enhance DNA-CREB/ATF1 interactions.

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Section: Discussionsupporting

confidence: 83%

Proinsulin C-peptide activates cAMP response element-binding proteins through the p38 mitogen-activated protein kinase pathway in mouse lung capillary endothelial cells

Kitamura

Kimura

Jung

et al. 2002

Biochemical Journal

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“…Secretion randomness of those series was determined using two different measures of secretion irregularity (ApEn and IpID). The insulin half-life determined in this study was comparable to previously published data, where it was determined by a range of different methods (20)(21)(22). The frequency of insulin pulses found in the present study was higher and the interpulse interval was shorter (non-diabetic group 11.3 Ϯ 2.5 pulses/90 min; 8.4 Ϯ 2.4 min) than some older studies (interpulse interval 11-13 min) (1,3,4), and similar to more recent studies (number of insulin pulses 11.8 Ϯ 0.9 per 90 min; interpulse interval 4.1 to 6.5 min) (10,23).…”

Section: Insulin Sensitivitysupporting

confidence: 86%

Effect of insulin sensitivity on pulsatile insulin secretion

Žarković

Ćirić²,

Stojanović³

et al. 1999

European Journal of Endocrinology

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Objective: The aim of the study was to determine whether derangements in insulin pulsatility are related to the presence of insulin resistance or whether these changes occur only in non-insulindependent diabetes mellitus (NIDDM). Design and methods:The study included 26 obese, 11 NIDDM and 10 control subjects. The obese group was divided into a low insulin (plasma insulin <20 mU/l, OLI, 14 subjects) and a high insulin (OHI, 12 subjects) group. For pulsatility analysis blood was sampled every 2 min for 90 min. Pulsatility analysis was carried out using the PulsDetekt program. The insulin secretion randomness was quantified using interpulse interval deviation (IpID) and approximate entropy (ApEn). Conclusions: Decrease in insulin sensitivity was correlated with the reduction of insulin secretion regularity. Therefore irregular insulin secretion is related to a reduction in insulin sensitivity, and it is not unique to NIDDM.

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“…Maximal phosphorylation occurred within 1 min and at 1 nM C-peptide. The effective concentrations of C-peptide were comparable with physiological levels (0.1-1.0 nM) of C-peptide in the circulation [26][27][28], and also with the association constant (K ass ) value (2.0-3.3 nM) obtained by a binding study in itro [13]. Because MAPK phosphorylation by C-peptide accompanied comparable increases in the catalytic activity of MAPK and the activation of MEK, our results therefore suggest that C-peptide can activate the MAPK cascade under physiological conditions.…”

Section: Discussionmentioning

confidence: 53%

Proinsulin C-peptide rapidly stimulates mitogen-activated protein kinases in Swiss 3T3 fibroblasts: requirement of protein kinase C, phosphoinositide 3-kinase and pertussis toxin-sensitive G-protein

et al. 2001

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It has been demonstrated that proinsulin C-peptide possesses several biological activities and that its specific binding sites are present on the surface of cell membranes. However, the molecular and cellular mechanisms of C-peptide actions are poorly known. In the present study we examined the possible involvement of the mitogen-activated protein kinase (MAPK) pathway in C-peptide effects. C-peptide induced the phosphorylation of MAPK [p44 extracellular signal-regulated kinase 1 (ERK1) and p42 ERK2] in Swiss 3T3 and 3T3-F442A fibroblasts but not in 3T3-L1 fibroblasts and some other cell lines such as L(6)E(9) muscle cells. In Swiss 3T3 cells, C-peptide-induced phosphorylation of MAPK was dependent on time and concentration, being maximal at 1 min and at 1 nM C-peptide and was accompanied by an increase in MAPK activity and MAPK kinase (MEK) phosphorylation. The MAPK phosphorylation by C-peptide was abolished by treatment with pertussis toxin (PTX) and also with a MEK inhibitor, PD 98059. In addition, MAPK phosphorylation was attenuated by treatment with a phosphoinositide 3-kinase (PI-3K) inhibitor, wortmannin, and with a protein kinase C (PKC) inhibitor, GF109203X, and by down-regulation of PKC by prolonged treatment with PMA. Similar effects of the inhibitors and PTX were found on the MAPK phosphorylation induced by neuropeptide Y. These results suggest that C-peptide activates MAPK through a putative G(i)/G(o)-linked receptor for C-peptide and through PI-3K-dependent and PKC-dependent pathways.

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Prolonged Plasma Half-Life of Insulin in Patients with a Genetic Defect of High Affinity Binding Sites

Cited by 13 publications

References 8 publications

Proinsulin C-peptide activates cAMP response element-binding proteins through the p38 mitogen-activated protein kinase pathway in mouse lung capillary endothelial cells

Proinsulin C-peptide activates cAMP response element-binding proteins through the p38 mitogen-activated protein kinase pathway in mouse lung capillary endothelial cells

Effect of insulin sensitivity on pulsatile insulin secretion

Proinsulin C-peptide rapidly stimulates mitogen-activated protein kinases in Swiss 3T3 fibroblasts: requirement of protein kinase C, phosphoinositide 3-kinase and pertussis toxin-sensitive G-protein

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