scholarly journals Effects of cellular ATP depletion on glucose transport and insulin signaling in 3T3-L1 adipocytes

2001 ◽  
Vol 280 (3) ◽  
pp. E428-E435 ◽  
Author(s):  
Jione Kang ◽  
Emma Heart ◽  
Chin K. Sung
Keyword(s):  
Insulin Resistance ◽  
Glucose Transport ◽  
Insulin Signaling ◽  
Atp Depletion ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Insulin Stimulation ◽  
Glut 1 ◽  
Induce Insulin Resistance ◽  
In Cells

Glucosamine induced insulin resistance in 3T3-L1 adipocytes, which was associated with a 15% decrease in cellular ATP content. To study the role of ATP depletion in insulin resistance, we employed sodium azide (NaN3) and dinitrophenol (DNP), which affect mitochondrial oxidative phosphorylation, to achieve a similar 15% ATP depletion. Unlike glucosamine, NaN3 and DNP markedly increased basal glucose transport, and the increased basal glucose transport was associated with increased GLUT-1 content in the plasma membrane without changes in total GLUT-1 content. These agents, like glucosamine, did not affect the early insulin signaling that is implicated in insulin stimulation of glucose transport. In cells with a severe 40% ATP depletion, basal glucose transport was similarly elevated, and insulin-stimulated glucose transport was similar in cells with 15% ATP depletion. In these cells, however, early insulin signaling was severely diminished. These data suggest that cellular ATP depletion by glucosamine, NaN3, and DNP exerts differential effects on basal and insulin-stimulated glucose transport and that ATP depletion per se does not induce insulin resistance in 3T3-L1 adipocytes.

Hepatic overexpression of a dominant negative form of raptor enhances Akt phosphorylation and restores insulin sensitivity in K/KAy mice

2008 ◽  
Vol 294 (4) ◽  
pp. E719-E725 ◽  
Author(s):  
Yuko Koketsu ◽  
Hideyuki Sakoda ◽  
Midori Fujishiro ◽  
Akifumi Kushiyama ◽  
Yasushi Fukushima ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Insulin Signaling ◽  
Dominant Negative ◽  
Insulin Stimulation ◽  
Kinase Activation ◽  
Akt Phosphorylation ◽  
Induce Insulin Resistance ◽  
Dominant Negative Form ◽  
Negative Form

Several serine/threonine kinases reportedly phosphorylate serine residues of IRS-1 and thereby induce insulin resistance. In this study, to investigate the effect of mTOR/raptor on insulin signaling and metabolism in K/KAy mice with genetic obesity-associated insulin resistance, a dominant negative raptor, COOH-terminally deleted raptor (raptor-ΔCT), was overexpressed in the liver via injection of its adenovirus into the circulation. Hepatic raptor-ΔCT expression levels were 1.5- to 4-fold that of endogenously expressed raptor. Glucose tolerance in raptor-ΔCT-overexpressing mice improved significantly compared with that of LacZ-overexpressing mice. Insulin-induced activation of p70S6 kinase (p70S6k) was significantly suppressed in the livers of raptor-ΔCT overexpressing mice. In addition, insulin-induced IRS-1, Ser307, and Ser636/639 phosphorylations were significantly suppressed in the raptor-ΔCT-overexpressing liver, whereas tyrosine phosphorylation of IRS-1 was increased. PI 3-kinase activation in response to insulin stimulation was increased approximately twofold, and Akt phosphorylation was clearly enhanced under both basal and insulin-stimulated conditions in the livers of raptor-ΔCT mice. Thus, our data indicate that suppression of the mTOR/p70S6k pathway leads to improved glucose tolerance in K/KAy mice. These observations may contribute to the development of novel antidiabetic agents.

scholarly journals Autotaxin Is Regulated by Glucose and Insulin in Adipocytes

Endocrinology ◽  
2017 ◽  
Vol 158 (4) ◽  
pp. 791-803 ◽  
Author(s):  
Kenneth D’Souza ◽  
Daniel A. Kane ◽  
Mohamed Touaibia ◽  
Erin E. Kershaw ◽  
Thomas Pulinilkunnil ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lysophosphatidic Acid ◽  
Insulin Signaling ◽  
Mitochondrial Respiration ◽  
Hormonal Regulation ◽  
H2o2 Production ◽  
Dependent Manner ◽  
Insulin Stimulation ◽  
Insulin Sensitizer

Abstract Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid. Despite recent studies implicating adipose-derived ATX in metabolic disorders including obesity and insulin resistance, the nutritional and hormonal regulation of ATX in adipocytes remains unclear. The current study examined the regulation of ATX in adipocytes by glucose and insulin and the role of ATX in adipocyte metabolism. Induction of insulin resistance in adipocytes with high glucose and insulin concentrations increased ATX secretion, whereas coincubation with the insulin sensitizer, rosiglitazone, prevented this response. Moreover, glucose independently increased ATX messenger RNA (mRNA), protein, and activity in a time- and concentration-dependent manner. Glucose also acutely upregulated secreted ATX activity in subcutaneous adipose tissue explants. Insulin elicited a biphasic response. Acute insulin stimulation increased ATX activity in a PI3Kinase-dependent and mTORC1-independent manner, whereas chronic insulin stimulation decreased ATX mRNA, protein, and activity. To examine the metabolic role of ATX in 3T3-L1 adipocytes, we incubated cells with the ATX inhibitor, PF-8380, for 24 hours. Whereas ATX inhibition increased the expression of peroxisome proliferator–activated receptor-γ and its downstream targets, insulin signaling and mitochondrial respiration were unaffected. However, ATX inhibition enhanced mitochondrial H2O2 production. Taken together, this study suggests that ATX secretion from adipocytes is differentially regulated by glucose and insulin. This study also suggests that inhibition of autocrine/paracrine ATX–lysophosphatidic acid signaling does not influence insulin signaling or mitochondrial respiration, but increases reactive oxygen species production in adipocytes.

Transferrin and iron induce insulin resistance of glucose transport in adipocytes

Metabolism ◽  
2006 ◽  
Vol 55 (8) ◽  
pp. 1042-1045 ◽  
Author(s):  
Allan Green ◽  
Robin Basile ◽  
John M. Rumberger
Keyword(s):  
Insulin Resistance ◽  
Glucose Transport ◽  
Induce Insulin Resistance

scholarly journals Age and tissue specific differences in the development of acute insulin resistance following injury

2009 ◽  
Vol 203 (3) ◽  
pp. 365-374 ◽  
Author(s):  
Lidong Zhai ◽  
Joseph L Messina
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Signaling ◽  
Intracellular Signaling ◽  
Male Rats ◽  
Hepatic Insulin Resistance ◽  
Surgical Trauma ◽  
Induce Insulin Resistance ◽  
Old Rats ◽  
Effect Of Age

Injuries, hemorrhage, sepsis, burn, and critical illnesses all induce insulin resistance, and insulin resistance is strongly associated with advancing age. However, the effect of age on injury induced insulin resistance is not well studied. We performed surgical trauma in male rats of three different ages (3-, 6-, and 10-weeks old). Rats were either hemorrhaged to a mean arterial pressure of 35–40 mmHg and subsequently maintained at that pressure for up to 90 min, or maintained without hemorrhage as controls. Results indicate that insulin-induced intracellular signaling was diminished in liver and skeletal muscle of 6- and 10-week old rats following trauma and hemorrhage. In even younger rats, immediately post-weaning (∼3 weeks of age), insulin signaling was lost in liver, but not in skeletal muscle. Glucocorticoids can play a role in the chronic development of insulin resistance. Our results demonstrate that corticosterone levels were increased in 6- and 10-week old animals following hemorrhage, but little change was measured in 3-week old animals. Blockade of glucocorticoid synthesis prevented the development of insulin resistance in skeletal muscle, but not in liver of 6- and 10-week old rats. Moreover, skeletal muscle glucocorticoid receptor levels increased dramatically between 3 and 6 weeks of age. These results indicate that trauma and hemorrhage-induced hepatic insulin resistance occurs at all ages tested. However, there is no development of insulin resistance following trauma and hemorrhage in skeletal muscle of post-weaning rats. In skeletal muscle of 6- and 10-week old rats, inhibition of glucocorticoid levels prevents the development of insulin resistance.

scholarly journals Role of Neu-p11/luzindole in the regulation of insulin signaling pathways and insulin resistance

2016 ◽  
Vol 48 (5) ◽  
pp. 485-486
Author(s):  
Xiuping Li ◽  
Shichang Cai ◽  
Weidong Yin ◽  
Xiaobo Hu ◽  
Sujun Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathways ◽  
Insulin Signaling

scholarly journals Stimulation of glucose transport in Clone 9 cells by insulin and thyroid hormone: role of GLUT-1 activation

1996 ◽  
Vol 1314 (1-2) ◽  
pp. 140-146 ◽  
Author(s):  
Mangala Shetty ◽  
Ashok K Kuruvilla ◽  
Faramarz Ismail-Beigi ◽  
John N Loeb
Keyword(s):  
Thyroid Hormone ◽  
Glucose Transport ◽  
Glut 1 ◽  
Stimulation Of

scholarly journals Translocation of the brain-type glucose transporter largely accounts for insulin stimulation of glucose transport in BC3H-1 myocytes

1990 ◽  
Vol 269 (3) ◽  
pp. 597-601 ◽  
Author(s):  
D M Calderhead ◽  
K Kitagawa ◽  
G E Lienhard ◽  
G W Gould
Keyword(s):  
Glucose Transport ◽  
Glucose Transporter ◽  
Fold Increase ◽  
The Other ◽  
Insulin Stimulation ◽  
Glut 1 ◽  
Glut 4 ◽  
Rat Soleus Muscle ◽  
The Brain ◽  
Stimulation Of

Insulin-stimulated glucose transport was examined in BC3H-1 myocytes. Insulin treatment lead to a 2.7 +/- 0.3-fold increase in the rate of deoxyglucose transport and, under the same conditions, a 2.1 +/- 0.1-fold increase in the amount of the brain-type glucose transporter (GLUT 1) at the cell surface. It has been shown that some insulin-responsive tissues express a second, immunologically distinct, transporter, namely GLUT 4. We report here that BC3H-1 myocytes and C2 and G8 myotubes express only GLUT 1; in contrast, rat soleus muscle and heart express 3-4 times higher levels of GLUT 4 than GLUT 1. Thus translocation of GLUT 1 can account for most, if not all, of the insulin stimulation of glucose transport in BC3H-1 myocytes. On the other, hand, neither BC3H-1 myocytes nor the other muscle-cell lines are adequate as models for the study of insulin regulation of glucose transport in muscle tissue.

scholarly journals From population to neuron: exploring common mediators for metabolic problems and mental illnesses

2020 ◽  
Author(s):  
Yoichiro Takayanagi ◽  
Koko Ishizuka ◽  
Thomas M Laursen ◽  
Hiroshi Yukitake ◽  
Kun Yang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Signaling ◽  
Neuronal Cells ◽  
Population Data ◽  
Epidemiological Data ◽  
Population Based ◽  
Mental Illnesses ◽  
Insulin Stimulation ◽  
Physical Conditions ◽  
Metabolic Conditions

Major mental illnesses such as schizophrenia (SZ) and bipolar disorder (BP) frequently accompany metabolic conditions, but their relationship is still unclear, in particular at the mechanistic level. We implemented an approach of "from population to neuron", combining population-based epidemiological analysis with neurobiological experiments using cell and animal models based on a hypothesis built from the epidemiological study. We characterized high-quality population data, olfactory neuronal cells biopsied from patients with SZ or BP, and healthy subjects, as well as mice genetically modified for insulin signaling. We accessed the Danish Registry and observed (1) a higher incidence of diabetes in people with SZ or BP and (2) higher incidence of major mental illnesses in people with diabetes in the same large cohort. These epidemiological data suggest the existence of common pathophysiological mediators in both diabetes and major mental illnesses. We hypothesized that molecules associated with insulin resistance might be such common mediators, and then validated the hypothesis by using two independent sets of olfactory neuronal cells biopsied from patients and healthy controls. In the first set, we confirmed an enrichment of insulin signaling-associated molecules among the genes that were significantly different between SZ patients and controls in unbiased expression profiling data. In the second set, olfactory neuronal cells from SZ and BP patients who were not pre-diabetic or diabetic showed reduced IRS2 tyrosine phosphorylation upon insulin stimulation, indicative of insulin resistance. These cells also displayed an upregulation of IRS1 protein phosphorylation at serine-312 at baseline (without insulin stimulation), further supporting the concept of insulin resistance in olfactory neuronal cells from SZ patients. Finally, Irs2 knockout mice showed an aberrant response to amphetamine, which is also observed in some patients with major mental illnesses. The bi-directional relationships between major mental illnesses and diabetes suggest that there may be common pathophysiological mediators associated with insulin resistance underlying these mental and physical conditions.

scholarly journals Potential Roles of Adipocyte Extracellular Vesicle–Derived miRNAs in Obesity-Mediated Insulin Resistance

2020 ◽  
Author(s):  
Yujeong Kim ◽  
Ok-Kyung Kim
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Metabolic Disorders ◽  
Extracellular Vesicle ◽  
Extracellular Mirnas

ABSTRACT Recently, extracellular microRNAs (miRNAs) from adipose tissue have been shown to be involved in the development of insulin resistance. Here, we summarize several mechanisms explaining the pathogenesis of obesity-induced insulin resistance and associated changes in the expression of obesity-associated extracellular miRNAs. We discuss how miRNAs, particularly miR-27a, miR-34a, miR-141-3p, miR-155, miR210, and miR-222, in extracellular vesicles secreted from the adipose tissue can affect the insulin signaling pathway in metabolic tissue. Understanding the role of these miRNAs will further support the development of therapeutics for obesity and metabolic disorders such as type 2 diabetes.

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