Continually high insulin levels impair Akt phosphorylation and glucose transport in human myoblasts

Bertacca, A; Ciccarone, Annamaria; Cecchetti, P; Vianello, Barbara; Laurenza, Incoronata; Maffei, Margherita; Chiellini, Chiara; Prato, Stefano Del; Benzi, Luca

doi:10.1016/j.metabol.2005.06.019

Cited by 38 publications

(29 citation statements)

References 33 publications

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“…Some arms of the insulin signaling cascade remain active in insulin-resistant liver (14). In addition, the hyperinsulinemic conditions used in this study have been shown to cause insulin resistance in cultured cells (15). Therefore, determining whether it is insulin action or insulin resistance that deactivates lipin 1␤ gene expression will require further study.…”

Section: Discussionmentioning

confidence: 94%

Hepatic Lipin 1β Expression Is Diminished in Insulin-Resistant Obese Subjects and Is Reactivated by Marked Weight Loss

et al. 2007

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OBJECTIVE-Lipin 1 plays critical roles in controlling energy metabolism. We sought to determine the expression of lipin 1 isoforms (lipin 1␣ and -␤) in liver and adipose tissue of obese subjects and to evaluate cellular mechanisms involved in the regulation of lipin 1 expression by physiologic stimuli. RESEARCH DESIGN AND METHODS-The expression of lipin 1␣ and -␤ was quantified in liver and adipose tissue of extremely obese (average BMI 60.8 kg/m 2 ) human subjects undergoing gastric bypass surgery (GBS). Second, the expression of lipin 1 was evaluated in HepG2 cells in response to overexpression of peroxisome proliferator-activated receptor-␥ coactivator (PGC)-1␣ under normal or hyperinsulinemic conditions. RESULTS-The expression of lipin 1␤ in liver and adipose tissue was inversely related to BMI, fasting plasma insulin concentration, and the homeostasis model assessment of insulin resistance but was significantly increased by marked weight loss and insulin sensitization following GBS. Hepatic lipin 1␤ mRNA levels were strongly correlated with the expression of PGC-1␣, and overexpression of PGC-1␣ in HepG2 cells increased lipin 1 expression. Conversely, hyperinsulinemic culture conditions downregulated the expression of lipin 1␤, PGC-1␣, and their known target genes involved in mitochondrial metabolism in HepG2 cells. Finally, overexpression of lipin 1␤ or PGC-1␣ reversed the effect of hyperinsulinemia on the expression of their target genes.CONCLUSIONS-These studies suggest that hepatic lipin 1␤ and PGC-1␣ expression are downregulated by obesity and obesity-related metabolic perturbations in human subjects, likely due to alterations in insulin concentration or sensitivity. Diabetes

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Section: Discussionmentioning

confidence: 94%

Hepatic Lipin 1β Expression Is Diminished in Insulin-Resistant Obese Subjects and Is Reactivated by Marked Weight Loss

et al. 2007

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“…The result is glucose intolerance and hyperglycemia, and subsequent type 2 diabetes. In addition, hyperinsulinemia may aggravate insulin resistance by interfering with insulinsignaling pathways and further exacerbating insulin resistance [28][29][30].…”

Section: Metabolic Syndrome With Insulin Resistancementioning

confidence: 99%

Metabolic syndrome, diabetes, and hyperuricemia

Hsieh

Chang

2013

Current Opinion in Rheumatology

372

239

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“…Whereas in liver insulin stimulates Akt phosphorylation and inhibits de novo glucose production, in muscle Akt phosphorylation is not stimulated, but in contrast glucose transport and storage are enhanced. In mammals persistent hyperinsulinaemia leads to impaired insulin signalling through Akt, glucose transport, storage and glucose utilization in muscle (Bertacca et al, 2005;Del Prato et al, 1994). In this context, Akt phosphorylation in muscle seems to correlate with different biological effects on insulin-sensitive processes in trout in comparison with mammals.…”

Section: Chronic Insulin Administration: Metabolic Regulation In Livementioning

confidence: 99%

Insulin-induced hypoglycaemia is co-ordinately regulated by liver and muscle during acute and chronic insulin stimulation in rainbow trout (Oncorhynchus mykiss)

Polakof

Skiba‐Cassy

Choubert

et al. 2010

Journal of Experimental Biology

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SUMMARYThe relative glucose intolerance of carnivorous fish species is often proposed to be a result of poor peripheral insulin action or possibly insulin resistance. In the present study, data from aortic cannulated rainbow trout receiving bovine insulin (75 mIU kg -1 ) injections show for the first time their ability to clear glucose in a very efficient manner. In another set of experiments, mRNA transcripts and protein phosphorylation status of proteins controlling glycaemia and glucose-related metabolism were studied during both acute and chronic treatment with bovine insulin. Our results show that fasted rainbow trout are well adapted at the molecular level to respond to increases in circulating insulin levels, and that this hormone is able to potentially improve glucose distribution and uptake by peripheral tissues. After acute insulin administration we found that to counter-regulate the insulininduced hypoglycaemia, trout metabolism is strongly modified. This short-term, efficient response to hypoglycaemia includes a rapid, coordinated response involving the reorganization of muscle and liver metabolism. During chronic insulin treatment some of the functions traditionally attributed to insulin actions in mammals were observed, including increased mRNA levels of glucose transporters and glycogen storage (primarily in the muscle) as well as decreased mRNA levels of enzymes involved in de novo glucose production (in the liver). Finally, we show that the rainbow trout demonstrates most of the classic metabolic adjustments employed by mammals to efficiently utilize glucose in the appropriate insulin context.

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Continually high insulin levels impair Akt phosphorylation and glucose transport in human myoblasts

Cited by 38 publications

References 33 publications

Hepatic Lipin 1β Expression Is Diminished in Insulin-Resistant Obese Subjects and Is Reactivated by Marked Weight Loss

Hepatic Lipin 1β Expression Is Diminished in Insulin-Resistant Obese Subjects and Is Reactivated by Marked Weight Loss

Metabolic syndrome, diabetes, and hyperuricemia

Insulin-induced hypoglycaemia is co-ordinately regulated by liver and muscle during acute and chronic insulin stimulation in rainbow trout (Oncorhynchus mykiss)

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