Insulin secretion and signaling in response to dietary restriction and subsequent re-alimentation in cattle

2015 ◽  
Vol 47 (8) ◽  
pp. 344-354 ◽  
Author(s):  
Kate Keogh ◽  
David A. Kenny ◽  
Alan K. Kelly ◽  
Sinéad M. Waters
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Dietary Restriction ◽  
Insulin Signaling ◽  
Compensatory Growth ◽  
Insulin Response ◽  
Insulin Signaling Pathway ◽  
Longissimus Dorsi ◽  
Period 2 ◽  
Ad Libitum

The objectives of this study were to examine systemic insulin response to a glucose tolerance test (GTT) and transcript abundance of genes of the insulin signaling pathway in skeletal muscle, during both dietary restriction and re-alimentation-induced compensatory growth. Holstein Friesian bulls were blocked to one of two groups: 1) restricted feed allowance for 125 days ( period 1) (RES, n = 15) followed by ad libitum feeding for 55 days ( period 2) or 2) ad libitum access to feed throughout (periods 1 and 2) (ADLIB, n = 15). On days 90 and 36 of periods 1 and 2, respectively, a GTT was performed. M. longissimus dorsi biopsies were harvested from all bulls on days 120 and 15 of periods 1 and 2, respectively, and RNA-Seq analysis was performed. RES displayed a lower growth rate during period 1 (RES: 0.6 kg/day, ADLIB: 1.9 kg/day; P < 0.001), subsequently gaining more during re-alimentation (RES: 2.5 kg/day, ADLIB: 1.4 kg/day; P < 0.001). Systemic insulin response to glucose administration was lower in RES in period 1 ( P < 0.001) with no difference observed during period 2. The insulin signaling pathway in M. longissimus dorsi was enriched ( P < 0.05) in response to dietary restriction but not during re-alimentation ( P > 0.05). Genes differentially expressed in the insulin signaling pathway suggested a greater sensitivity to insulin in skeletal muscle, with pleiotropic effects of insulin signaling interrupted during dietary restriction. Collectively, these results indicate increased sensitivity to glucose clearance and skeletal muscle insulin signaling during dietary restriction; however, no overall role for insulin was apparent in expressing compensatory growth.

scholarly journals MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle

2020 ◽  
Author(s):  
Clothilde Philouze ◽  
Sophie Turban ◽  
Béatrice Cremers ◽  
Audrey Caliez ◽  
Gwladys Lamarche ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Insulin Response ◽  
Muscle Cells ◽  
Insulin Signaling Pathway ◽  
Akt Phosphorylation ◽  
Impaired Insulin

AbstractIn type 2 diabetes (T2D), both muscle and liver are severely resistant to insulin action. Muscle insulin resistance accounts for more than 80% of the impairment in total body glucose disposal in T2D patients and is often characterized by an impaired insulin signaling. Mitsugumin 53 (MG53), a muscle-specific TRIM family protein initially identified as a key regulator of cell membrane repair machinery has been suggested to be a critical regulator of muscle insulin signaling pathway by acting as ubiquitin E3 ligase targeting both the insulin receptor and insulin receptor substrate 1 (IRS1). Here, we show using in vitro and in vivo approaches that MG53 is not a critical regulator of insulin signaling and glucose homeostasis. First, MG53 expression is not consistently regulated in skeletal muscle from various preclinical models of insulin resistance. Second, MG53 gene knock-down in muscle cells does not lead to impaired insulin response as measured by Akt phosphorylation on Serine 473 and glucose uptake. Third, recombinant human MG53 does not alter insulin response in both differentiated C2C12 and human skeletal muscle cells. Fourth, ectopic expression of MG53 in HEK293 cells lacking endogenous MG53 expression fails to alter insulin response as measured by Akt phosphorylation. Finally, both male and female mg53 −/− mice were not resistant to high fat induced obesity and glucose intolerance compared to wild-type mice. Taken together, these results strongly suggest that MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle.

scholarly journals MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245179
Author(s):  
Clothilde Philouze ◽  
Sophie Turban ◽  
Beatrice Cremers ◽  
Audrey Caliez ◽  
Gwladys Lamarche ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Insulin Response ◽  
Muscle Cells ◽  
Insulin Signaling Pathway ◽  
Akt Phosphorylation ◽  
Impaired Insulin

In type 2 diabetes (T2D), both muscle and liver are severely resistant to insulin action. Muscle insulin resistance accounts for more than 80% of the impairment in total body glucose disposal in T2D patients and is often characterized by an impaired insulin signaling. Mitsugumin 53 (MG53), a muscle-specific TRIM family protein initially identified as a key regulator of cell membrane repair machinery has been suggested to be a critical regulator of muscle insulin signaling pathway by acting as ubiquitin E3 ligase targeting both the insulin receptor and insulin receptor substrate 1 (IRS1). Here, we show using in vitro and in vivo approaches that MG53 is not a critical regulator of insulin signaling and glucose homeostasis. First, MG53 expression is not consistently regulated in skeletal muscle from various preclinical models of insulin resistance. Second, MG53 gene knock-down in muscle cells does not lead to impaired insulin response as measured by Akt phosphorylation on Serine 473 and glucose uptake. Third, recombinant human MG53 does not alter insulin response in both differentiated C2C12 and human skeletal muscle cells. Fourth, ectopic expression of MG53 in HEK293 cells lacking endogenous MG53 expression fails to alter insulin response as measured by Akt phosphorylation. Finally, both male and female mg53 -/- mice were not resistant to high fat induced obesity and glucose intolerance compared to wild-type mice. Taken together, these results strongly suggest that MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle.

scholarly journals Activation of PI3K/Akt Signaling Pathway in Rat Hypothalamus Induced by an Acute Oral Administration of D-Pinitol

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2268
Author(s):  
Dina Medina-Vera ◽  
Juan Antonio Navarro ◽  
Rubén Tovar ◽  
Cristina Rosell-Valle ◽  
Alfonso Gutiérrez-Adan ◽  
...  
Keyword(s):  
Oral Administration ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Insulin Response ◽  
Pharmacological Action ◽  
Akt Signaling ◽  
Insulin Signaling Pathway ◽  
Acute Administration ◽  
Insulin Sensitizer ◽  
Peripheral Tissues

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN. The PI3K/Akt-associated proteins were quantified by Western blot in terms of phosphorylation and total expression. Results indicate that the acute administration of DPIN induced time-dependent phosphorylation of PI3K/Akt and its related substrates within the hypothalamus, indicating an activation of the insulin signaling pathway. This profile is consistent with DPIN as an insulin sensitizer since we also found a decrease in the circulating concentration of this hormone. Overall, the present study shows the pharmacological action of DPIN in the hypothalamus through the PI3K/Akt pathway when giving in fasted animals. These findings suggest that DPIN might be a candidate to treat brain insulin-resistance associated disorders by activating insulin response beyond the insulin receptor.

Effect of Peroral Administration of Chromium on Insulin Signaling Pathway in Skeletal Muscle Tissue of Holstein Calves

2017 ◽  
Vol 180 (2) ◽  
pp. 223-232 ◽  
Author(s):  
Ljubomir Jovanović ◽  
Marija Pantelić ◽  
Radiša Prodanović ◽  
Ivan Vujanac ◽  
Miloje Đurić ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Muscle Tissue ◽  
Insulin Signaling ◽  
Insulin Signaling Pathway ◽  
Skeletal Muscle Tissue ◽  
Peroral Administration ◽  
Holstein Calves

scholarly journals Intracellular pH Regulation of Skeletal Muscle in the Milieu of Insulin Signaling

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2910
Author(s):  
Dheeraj Kumar Posa ◽  
Shahid P. Baba
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Signaling Pathway ◽  
Intracellular Ph ◽  
Cross Talk ◽  
Insulin Signaling ◽  
Insulin Signaling Pathway ◽  
Glycolytic Pathway ◽  
Insulin Responses

Type 2 diabetes (T2D), along with obesity, is one of the leading health problems in the world which causes other systemic diseases, such as cardiovascular diseases and kidney failure. Impairments in glycemic control and insulin resistance plays a pivotal role in the development of diabetes and its complications. Since skeletal muscle constitutes a significant tissue mass of the body, insulin resistance within the muscle is considered to initiate the onset of diet-induced metabolic syndrome. Insulin resistance is associated with impaired glucose uptake, resulting from defective post-receptor insulin responses, decreased glucose transport, impaired glucose phosphorylation, oxidation and glycogen synthesis in the muscle. Although defects in the insulin signaling pathway have been widely studied, the effects of cellular mechanisms activated during metabolic syndrome that cross-talk with insulin responses are not fully elucidated. Numerous reports suggest that pathways such as inflammation, lipid peroxidation products, acidosis and autophagy could cross-talk with insulin-signaling pathway and contribute to diminished insulin responses. Here, we review and discuss the literature about the defects in glycolytic pathway, shift in glucose utilization toward anaerobic glycolysis and change in intracellular pH [pH]i within the skeletal muscle and their contribution towards insulin resistance. We will discuss whether the derangements in pathways, which maintain [pH]i within the skeletal muscle, such as transporters (monocarboxylate transporters 1 and 4) and depletion of intracellular buffers, such as histidyl dipeptides, could lead to decrease in [pH]i and the onset of insulin resistance. Further we will discuss, whether the changes in [pH]i within the skeletal muscle of patients with T2D, could enhance the formation of protein aggregates and activate autophagy. Understanding the mechanisms by which changes in the glycolytic pathway and [pH]i within the muscle, contribute to insulin resistance might help explain the onset of obesity-linked metabolic syndrome. Finally, we will conclude whether correcting the pathways which maintain [pH]i within the skeletal muscle could, in turn, be effective to maintain or restore insulin responses during metabolic syndrome.

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