Activation of phosphatidylinositol 3-kinase by insulin.

Ruderman, Neil B.; Kapeller, Rosana; White, Morris F.; Cantley, Lewis C.

doi:10.1073/pnas.87.4.1411

Cited by 508 publications

(296 citation statements)

References 35 publications

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“…Two classes of serine/ threonine kinases are known to act downstream of lipid PI 3-kinase, the serine/threonine kinase Akt, also known as protein kinase B (PKB), and the atypical PKC isoforms z and l (PKCz/l). Expression of Akt, mediated by activation of PI 3,4,5-triphoshate, is reported to induce the activation of the ribosomal protein S6 kinase (Downward, 1995), the inhibition of glycogen synthase kinase 3, and the inhibition of apoptotic cell responses (Ruderman et al, 1990;Li et al, 1999;BernalMizrachi et al, 2001). Bernal-Mizrachi et al (2001) and Tuttle et al (2001) suggest that PKB control B-cell size and growth.…”

Section: Insulin Receptor In Pancreatic B-cellmentioning

confidence: 99%

Pleiotropic effects of fatty acids on pancreatic β‐cells

Haber

Ximenes

Procópio

et al. 2002

Journal Cellular Physiology

148

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Hyperlipidemia is frequently associated with insulin resistance states as found in type 2 diabetes and obesity. Effects of free fatty acids (FFA) on pancreatic b-cells have long been recognized. Acute exposure of the pancreatic b-cell to FFA results in an increase of insulin release, whereas a chronic exposure results in desensitization and suppression of secretion. We recently showed that palmitate augments insulin release in the presence of non-stimulatory concentrations of glucose. Reduction of plasma FFA levels in fasted rats or humans severely impairs glucose-induced insulin release. These results imply that physiological plasma levels of FFA are important for b-cell function. Although, it has been accepted that fatty acid oxidation is necessary for its stimulation of insulin secretion, the possible mechanisms by which fatty acids (FA) affect insulin secretion are discussed in this review. Long-chain acylCoA (LC-CoA) controls several aspects of the b-cell function including activation of certain types of protein kinase C (PKC), modulation of ion channels, protein acylation, ceramide-and/or nitric oxide (NO)-mediated apoptosis, and binding to nuclear transcriptional factors. The present review also describes the possible effects of FA on insulin signaling. We showed for the first time that acute exposure of islets to palmitate upregulates the intracellular insulin-signaling pathway in pancreatic islets. Another aspect considered in this review is the source of FA for pancreatic islets. In addition to be exported to the medium, lipids can be transferred from leukocytes (macrophages) to pancreatic islets in co-culture. This process consists an additional source of FA that may plays a significant role to regulate insulin secretion.

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Section: Insulin Receptor In Pancreatic B-cellmentioning

confidence: 99%

Pleiotropic effects of fatty acids on pancreatic β‐cells

Haber

Ximenes

Procópio

et al. 2002

Journal Cellular Physiology

148

View full text Add to dashboard Cite

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“…Abbreviations: FcyR, Fc receptor for IgG; Pl, phosphatidylinositol; p85, 85-kDa subunit of Pl 3-kinase; PI-3P, PI 3.phosphate stimulating factor-I [21][22][23][24][25][26]. PI 3-kinase has also been activated after stimulation of a variety of the receptors lacking tyrosine kinase domains.…”

Section: Introductionmentioning

confidence: 99%

Specific association of phosphatidylinositol 3‐kinase with the protooncogene product Cbl in Fcγ receptor signaling

Matsuo

Hazeki

et al. 1996

FEBS Letters

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“…PI3-kinase activity was determined as described [28][29][30]. Briefly, confluent cells were incubated with or without 10 -7 mol/l insulin for 5 min at 37°C and lysed at 4°C in buffer A containing 1 % (v/v) Nonidet P- -subunit were used to monitor insulin receptor expression.…”

Section: Transient Expression Of Hir-wt Hir-djm and Hir-973 In Hekmentioning

confidence: 99%

A 973 valine to methionine mutation of the human insulin receptor: interaction with insulin-receptor substrate-1 and Shc in HEK 293 cells

et al. 1997

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Summary A population-based study in the Netherlands has recently demonstrated that a mutation of the human insulin receptor (HIR-973 valine to methionine) is associated with hyperglycaemia and an increased prevalence of non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present study was to assess whether this mutation leads to a functional alteration of the insulin receptor. We prepared the HIR-973 mutant by in vitro mutagenesis. This mutant was transiently overexpressed in HEK 293 cells either alone or together with insulin-receptor substrate-1 (IRS-1) or Shc. Insulin stimulated autophosphorylation, phosphorylation of the substrates IRS-1 and Shc as well as activation of phosphatidylinositol-3 (PI3)-kinase were studied. Autophosphorylation of HIR-973 and its susceptibility to hyperglycaemia induced inhibition was not different from HIR-wt. Human insulin receptor with a juxtamembrane deletion HIR-DJM which is known to impair HIR/IRS-1 interaction was used as control. While the HIR-DJM induces a reduced IRS-1 phosphorylation HIR-973 showed even a slightly increased ability to phosphorylate IRS-1 (n = 7, 115 % of control, p < 0.01). Shc phosphorylation was only mediated by HIR-wt and HIR-973 but not by HIR-DJM.Again a tendency to higher phosphorylation of Shc was seen with HIR-973 (n = 7, 109 % of control, NS). When PI3-kinase activity was measured in IRS-1 precipitates similar activity was found for HIR-wt and HIR-973 whereas PI3-kinase stimulation was reduced with HIR-DJM. In summary, the data suggest that HIR-973 does not impair the first steps of the insulin signalling cascade. It is therefore unlikely that this mutation may cause cellular insulin resistance. The close vicinity of this mutation to insulin receptor domains which are involved in IRS-1 and Shc binding may, however, alter the interaction of the insulin receptor with these substrates. This could explain the slightly increased insulin effect on tyrosine phosphorylation of these docking proteins. These characteristics of HIR-973 might have a compensatory function of impaired signal transduction further downstream of the signalling chain in this specific subgroup of NIDDM patients. [Diabetologia (1997[Diabetologia ( ) 40: 1135[Diabetologia ( -1140

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Activation of phosphatidylinositol 3-kinase by insulin.

Abstract: Insulin action appears to require the proteintyrosine kinase domain of the (3 subunit of the insulin receptor. Despite this, the identities and biochemical functions of the cellular targets of this tyrosine kinase are unknown. A phosphatidylinositol 3-kinase

Cited by 508 publications

References 35 publications

Pleiotropic effects of fatty acids on pancreatic β‐cells

Pleiotropic effects of fatty acids on pancreatic β‐cells

Specific association of phosphatidylinositol 3‐kinase with the protooncogene product Cbl in Fcγ receptor signaling

A 973 valine to methionine mutation of the human insulin receptor: interaction with insulin-receptor substrate-1 and Shc in HEK 293 cells

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