Calcium signaling in insulin action on striated muscle

Contreras‐Ferrat, Ariel; Lavandero, Sergio; Jaimovich, Enrique; Klip, Amira

doi:10.1016/j.ceca.2014.08.012

Cited by 43 publications

(40 citation statements)

References 84 publications

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“…Of interest, RyR are rapidly tyrosine phosphorylated upon activation in activated T-lymphocytes (Guse et al , 2001) and growth hormone can tyrosine phosphorylate RyR in a β-cell-derived cell line (Zhang et al , 2004). Prior work has also shown that insulin can elicit an increase in calcium release through activation of RyR in muscle cells (Contreras-Ferrat et al , 2014). Future studies are necessary to identify if RyR subtypes can respond differently to insulin, whether these effects are tissue specific, dependent on particular signaling pathways, or whether sarcoplasmic-endoplasmic Ca 2+ -ATPases (SERCAs) function also is sensitive to insulin.…”

Section: Discussionmentioning

confidence: 98%

Novel calcium-related targets of insulin in hippocampal neurons

et al. 2017

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Both insulin signaling disruption and Ca2+ dysregulation are closely related to memory loss during aging and increase the vulnerability to Alzheimer's disease (AD). In hippocampal neurons, aging-related changes in calcium regulatory pathways have been shown to lead to higher intracellular calcium levels and an increase in the Ca2+-dependent afterhyperpolarization (AHP), which is associated with cognitive decline. Recent studies suggest that insulin reduces the Ca2+-dependent AHP. Given the sensitivity of neurons to insulin and evidence that brain insulin signaling is reduced with age, insulin-mediated alterations in calcium homeostasis may underlie the beneficial actions of insulin in the brain. Indeed, increasing insulin signaling in the brain via intranasal delivery has yielded promising results such as improving memory in both clinical and animal studies. However, while several mechanisms have been proposed, few have focused on regulation on intracellular Ca2+. In the present study, we further examined the effects of acute insulin on calcium pathways in primary hippocampal neurons in culture. Using the whole-cell patch-clamp technique, we found that acute insulin delivery reduced voltage-gated calcium currents. Fura-2 imaging was used to also address acute insulin effects on spontaneous and depolarization-mediated Ca2+ transients. Results indicate that insulin reduced Ca2+ transients, which appears to have involved a reduction in ryanodine receptor function. Together, these results suggest insulin regulates pathways that control intracellular Ca2+ which may reduce the AHP and improve memory. This may be one mechanism contributing to improved memory recall in response to intranasal insulin therapy in the clinic.

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Section: Discussionmentioning

confidence: 98%

Novel calcium-related targets of insulin in hippocampal neurons

et al. 2017

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“…In hippocampal neurons, compounds that activate the insulin receptor also mobilize the AMPK-SIRT signaling axis with associated enhancement of mitochondrial function (Barhwal et al, 2015). Insulin can also boost intracellular Ca 2+ ion concentration (Contreras-Ferrat et al, 2014) which could trigger activation of an upstream activator of AMPK, namely Ca 2+ /calmodulin-dependent protein kinase kinase β (CaMKKβ) (Hawley et al, 2005; Hurley et al, 2005; Woods et al, 2005). Thus, insulin signaling and coordinated activation of AMPK could augment mitochondrial function in sensory neurons.…”

Section: Discussionmentioning

confidence: 99%

Insulin prevents aberrant mitochondrial phenotype in sensory neurons of type 1 diabetic rats

Aghanoori

Smith

Chowdhury

et al. 2017

Experimental Neurology

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Diabetic neuropathy affects approximately 50% of diabetic patients. Down-regulation of mitochondrial gene expression and function has been reported in both human tissues and in dorsal root ganglia (DRG) from animal models of type 1 and type 2 diabetes. We hypothesized that loss of direct insulin signaling in diabetes contributes to loss of mitochondrial function in DRG neurons and to development of neuropathy. Sensory neurons obtained from age-matched adult control or streptozotocin (STZ)-induced type 1 diabetic rats were cultured with or without insulin before determining mitochondrial respiration and expression of mitochondrial respiratory chain and insulin signaling-linked proteins. For in vivo studies age-matched control rats and diabetic rats with or without trace insulin supplementation were maintained for 5 months before DRG were analyzed for respiratory chain gene expression and cytochrome c oxidase activity. Insulin (10nM) significantly (P<0.5) increased phosphorylation of Akt and P70S6K by 4-fold and neurite outgrowth by 2-fold in DRG cultures derived from adult control rats. Insulin also augmented the levels of selective mitochondrial respiratory chain proteins and mitochondrial bioenergetics parameters in DRG cultures from control and diabetic rats, with spare respiratory capacity increased by up to 3-fold (P<0.05). Insulin-treated diabetic animals exhibited improved thermal sensitivity in the hind paw and had increased dermal nerve density compared to untreated diabetic rats, despite no effect on blood glucose levels. In DRG of diabetic rats there was suppressed expression of mitochondrial respiratory chain proteins and cytochrome c oxidase activity that was corrected by insulin therapy. Insulin elevates mitochondrial respiratory chain protein expression and function in sensory neurons and this is associated with enhanced neurite outgrowth and protection against indices of neuropathy.

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“…The relationship between calcium and glucose homeostasis has long been recognized, with case-control studies assessing calcium fractions dating back to 1960s (26). In parallel with observational work, experimental studies have described the role of calcium at the cellular and molecular level, clarifying fundamental second messenger functions in insulin secretion (3) and action (4,27).…”

Section: Discussionmentioning

confidence: 99%