High glucose attenuates insulin-induced mitogen-activated protein kinase phosphatase-1 (MKP-1) expression in vascular smooth muscle cells

Takehara, Naohumi; Kawabe, Jun‐ichi; Aizawa, Yoshiaki; Hasebe, Naoyuki; Kikuchi, Kenjiro

doi:10.1016/s0167-4889(00)00050-1

Cited by 12 publications

(12 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rat mesangial cells exposed to high glucose had decreased DUSP1 (3). In rat vascular smooth muscle cells, hyperglycemia inhibited insulin-induced DUSP1 and PI3K expression (37). Wortmannin, the PI3K inhibitor, blocked insulin- …”

Section: Discussionmentioning

confidence: 96%

Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components

Gilliam-Davis¹,

Gallagher²,

Payne

et al. 2011

Physiological Genomics

View full text Add to dashboard Cite

Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components. Physiol Genomics 43: 829 -835, 2011. First published May 3, 2011 doi:10.1152/physiolgenomics.00167.2010 rats, renin-angiotensin system (RAS) blockade for 1 yr with the angiotensin II type 1 (AT1) receptor blocker L-158,809 prevents age-related impairments in metabolic function, similar to transgenic rats with low glial angiotensinogen (Aogen). Brain RAS regulation may contribute to the benefits of long-term systemic AT1 antagonism. We assessed the mRNA of RAS components in the dorsomedial medulla of F344 rats at 3 (young; n ϭ 8) or 15 mo of age (old; n ϭ 7) and in rats treated from 3 to 15 mo of age with 20 mg/l of the AT1 receptor antagonist L-158,809 (OldϩL; n ϭ 6). Aogen and renin mRNA were lower in the young compared with old group. Angiotensin-converting enzyme (ACE) mRNA was lower in the old and OldϩL compared with the young group. ACE2 and neprilysin expression were significantly higher in OldϩL compared with young or old rats. AT1b, AT2, and Mas receptor mRNA were higher with treatment. Leptin receptor mRNA was lower in the old rats and this was prevented by L-158,809 treatment. Dual-specificity phosphatase 1 (DUSP1) mRNA was highest in the OldϩL group. Aggregate correlate summation revealed a positive relationship for Mas receptor mRNA with food intake. The findings provide evidence for regulation of dorsomedial medullary renin and Aogen mRNA during aging. Long-term AT1 receptor blockade increases the mRNA of the enzymes ACE2 and neprilysin and the MAS receptor, which could potentially shift the balance from ANG II to ANG-(1-7) and prevent age-related declines in the leptin receptor and its signaling pathway.angiotensinogen; Fischer 344 rats; leptin; aggregate correlate summation SYSTEMIC BLOCKADE OF the renin-angiotensin system (RAS) with angiotensin II type 1 (AT 1 ) receptor blockers or angiotensinconverting enzyme (ACE) inhibitors provides beneficial effects outside of the classic hemodynamic actions. RAS blockade improves many components of aging and reduces the onset of the metabolic syndrome and Type 2 diabetes (1,8,17,43). However, the precise mechanisms underlying the beneficial effects are not entirely known. During aging, there is a decline in the circulating (systemic) RAS, including angiotensin (ANG)-(1-7) (30), suggesting that the beneficial actions of RAS blockade are partly due to the suppression of ANG II in tissues. Many tissues and organs contain their own local RAS, including the kidney, heart, vessels, adrenal gland, pancreas, and brain (4, 25). Increased brain ANG II activates sympathetic outflow, inhibits the baroreflex, stimulates thirst, and contributes to neurogenic hypertension (25,36, 38). In rats with chronic renal failure, components of the brain RAS are upregulated, resulting in sympathetic overactivity and hypertension (29). Transgenic mice with increased production of brain ANG II developed hypertension and an increase in salt ...

show abstract

Section: Discussionmentioning

confidence: 96%

Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components

Gilliam-Davis¹,

Gallagher²,

Payne

et al. 2011

Physiological Genomics

View full text Add to dashboard Cite

show abstract

“…For instance, insulin has been shown to increase the expression of mitogen-activated protein kinase phosphatase (MKP-1) in a PI3K-dependent manner (Desbois-Mouthon et al, 2000;Takehara et al, 2000), and this phosphatase negatively regulates IL-6 and TNF-␣ production in endotoxemic mice (Chi et al, 2006). Furthermore, a recent study showed that insulin and a glycogen synthase kinase 3␤ inhibitor had similar anti-inflammatory effects in a rat model of sepsis (Dugo et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Insulin Activation of the Phosphatidylinositol 3-Kinase/Protein Kinase B (Akt) Pathway Reduces Lipopolysaccharide-Induced Inflammation in Mice

Kidd

Schabbauer

Luyendyk

et al. 2008

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Insulin is used to control pro-inflammatory hyperglycemia in critically ill patients. However, recent studies suggest that insulin-induced hypoglycemia may negate its beneficial effects in these patients. It is noteworthy that recent evidence indicates that insulin has anti-inflammatory effects that are independent of controlling hyperglycemia. To date, the mechanism by which insulin directly reduces inflammation has not been elucidated. It is well established that insulin activates phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling in many cell types. We and others have shown that this pathway negatively regulates LPS-induced signaling and pro-inflammatory cytokine production in monocytic cells. We hypothesized that insulin inhibits inflammation during endotoxemia by activation of the PI3K/Akt pathway. We used a nonhyperglycemic mouse model of endotoxemia to determine the effect of continuous administration of a low dose of human insulin on inflammation and survival. It is noteworthy that insulin treatment induced phosphorylation of Akt in muscle and adipose tissues but did not exacerbate lipopolysaccharide (LPS)-induced hypoglycemia. Insulin decreased plasma levels of interleukin-6, tumor necrosis factor-␣, monocyte chemotactic protein 1 (MCP1)/JE, and keratinocyte chemoattractant, and decreased mortality. The PI3K inhibitor wortmannin abolished the insulin-mediated activation of Akt and the reduction of chemokine and interleukin-6 levels. We conclude that insulin reduces LPS-induced inflammation in mice in a PI3K/Akt-dependent manner without affecting blood glucose levels.

show abstract

“…In turn, sustained vasodilation would plausibly lead to elevated glucose availability and thus counterregulatory failure due to hypothalamic overestimation of plasma glucose. Furthermore, ATII induces the expression of GLUT-1 (17) and MKP-1 (18), which some data suggest can act as a switch during hypoglycemia to stimulate phosphatidylinositol 3-kinase-mediated glucose metabolism (19,20). Clearly, the induction of GLUT-1, whose induction by chronic hypoglycemia had been previously reported (21), would plausibly serve a neuroprotective role by increasing the transport of glucose into the brain and by doing so lead to counterregulatory failure, as previously proposed (22).…”

Section: Discussionmentioning

confidence: 99%

Acute Induction of Gene Expression in Brain and Liver by Insulin-Induced Hypoglycemia

et al. 2005

View full text Add to dashboard Cite

The robust neuroendocrine counterregulatory responses induced by hypoglycemia protect the brain by restoring plasma glucose, but little is known about molecular responses to hypoglycemia that may also be neuroprotective. To clarify these mechanisms, we examined gene expression in hypothalamus, cortex, and liver 3 h after induction of mild hypoglycemia by a single injection of insulin, using cDNA microarray analysis and quantitative real-time PCR. Real-time PCR corroborated the induction of six genes (angiotensinogen, GLUT-1, inhibitor of B, inhibitor of DNA binding 1 [ID-1], Ubp41, and mitogen-activated protein kinase phosphatase-1 [MKP-1]) by insulin-induced hypoglycemia in the hypothalamus: five of these six genes in cortex and three (GLUT-1, angiotensinogen, and MKP-1) in liver. The induction was due to hypoglycemia and not hyperinsulinemia, since fasting (characterized by low insulin and glucose) also induced these genes. Four of these genes (angiotensinogen, GLUT-1, ID-1, and MKP-1) have been implicated in enhancement of glucose availability, which could plausibly serve a neuroprotective role during acute hypoglycemia but, if persistent, could also cause glucose-sensing mechanisms to overestimate plasma glucose levels, potentially causing hypoglycemia-induced counterregulatory failure. Although using cDNA microarrays with more genes, or microdissection, would presumably reveal further responses to hypoglycemia, these hypoglycemia-induced genes represent useful markers to assess molecular mechanisms mediating cellular responses to hypoglycemia. Diabetes 54:952-958, 2005

show abstract

High glucose attenuates insulin-induced mitogen-activated protein kinase phosphatase-1 (MKP-1) expression in vascular smooth muscle cells

Cited by 12 publications

References 25 publications

Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components

Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components

Insulin Activation of the Phosphatidylinositol 3-Kinase/Protein Kinase B (Akt) Pathway Reduces Lipopolysaccharide-Induced Inflammation in Mice

Acute Induction of Gene Expression in Brain and Liver by Insulin-Induced Hypoglycemia

Contact Info

Product

Resources

About