The insulin resistance is reversed by exogenous 3,5,3′triiodothyronine in type 2 diabetic Goto–Kakizaki rats by an inflammatory-independent pathway

Panveloski-Costa, Ana Carolina; Kuwabara, Wilson Mitsuo Tatagiba; Munhoz, Ana Cláudia; Lucena, Camila Ferraz; Curi, Rui; Carpinelli, Ângelo Rafael; Nunes, Maria Tereza

doi:10.1007/s12020-020-02208-5

Cited by 6 publications

(5 citation statements)

References 30 publications

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“…These rats display insulin sensitivity impairment and T2DM similar to highcaloric diet-induced obese animals. Interestingly, in contrast to the changes in rats submitted to diet-induced obesity, the increased expression of proinflammatory cytokines is not observed in the skeletal muscle and retroperitoneal adipose tissue depots of 16-week-old GK rats (3,38).…”

Section: Gk Rats: a Lean Model Of Type 2 Diabetes Mellituscontrasting

confidence: 56%

“…The Goto-Kakizaki (GK) rat, a spontaneous nonobese-T2DM animal model, was generated by selective inbreeding using glucose-intolerant Wistar rats with a hyperglycemic phenotype (15). Many studies have utilized GK rats to evaluate non-obese T2DM features, development, and complications (3,4,(36)(37)(38)(39). These rats display insulin sensitivity impairment and T2DM similar to highcaloric diet-induced obese animals.…”

Section: Gk Rats: a Lean Model Of Type 2 Diabetes Mellitusmentioning

confidence: 99%

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Reviewing physical exercise in non-obese diabetic Goto-Kakizaki rats

Galán

Serdan

Rodrigues

et al. 2022

Braz J Med Biol Res

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There is a high incidence of non-obese type 2 diabetes mellitus (non-obese-T2DM) cases, particularly in Asian countries, for which the pathogenesis remains mainly unclear. Interestingly, Goto-Kakizaki (GK) rats spontaneously develop insulin resistance (IR) and non-obese-T2DM, making them a lean diabetes model. Physical exercise is a non-pharmacological therapeutic approach to reduce adipose tissue mass, improving peripheral IR, glycemic control, and quality of life in obese animals or humans with T2DM. In this narrative review, we selected and analyzed the published literature on the effects of physical exercise on the metabolic features associated with non-obese-T2DM. Only randomized controlled trials with regular physical exercise training, freely executed physical activity, or skeletal muscle stimulation protocols in GK rats published after 2008 were included. The results indicated that exercise reduces plasma insulin levels, increases skeletal muscle glycogen content, improves exercise tolerance, protects renal and myocardial function, and enhances blood oxygen flow in GK rats.

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Section: Gk Rats: a Lean Model Of Type 2 Diabetes Mellituscontrasting

confidence: 56%

Section: Gk Rats: a Lean Model Of Type 2 Diabetes Mellitusmentioning

confidence: 99%

Reviewing physical exercise in non-obese diabetic Goto-Kakizaki rats

Galán

Serdan

Rodrigues

et al. 2022

Braz J Med Biol Res

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“…Binding of T3 upregulated GLUT4, which translocates to the plasma membrane in brown adipocytes and sequesters glucose, ultimately regulating gluconeogenesis and glycolysis (Obregon, 2014). Additionally, T3 treatment enhanced GLUT4 content in adipose and soleus muscle (Panveloski-Costa et al, 2020). Collectively, these data highlight the contributions of THs to the regulation of glucose metabolism in BAT and potentially thermogenesis and whole-body energetics.…”

Section: Livermentioning

confidence: 89%

“…Furthermore, GLUT4 has a TRE in its promoter along with carbohydrate responsive element binding protein (ChREBP), retinoic acid receptors (RAR), and cAMP response element (CRE). Binding of T3 upregulated GLUT4, which translocates to the plasma membrane in brown adipocytes and sequesters glucose, ultimately regulating gluconeogenesis and glycolysis (Obregon, 2014). Additionally, T3 treatment enhanced GLUT4 content in adipose and soleus muscle (Panveloski-Costa et al, 2020).…”

Section: Livermentioning

confidence: 99%

Thyroid hormones and the potential for regulating glucose metabolism in cardiomyocytes during insulin resistance and T2DM

Mendez

Ortiz

2021

Physiol Rep

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In order for the heart to maintain its continuous mechanical work and provide the systolic movement to uphold coronary blood flow, substantial synthesis of adenosine triphosphate (ATP) is required. Under normal conditions cardiac tissue utilizes roughly 70% fatty acids (FA), and 30% glucose for the production of ATP; however, during impaired metabolic conditions like insulin resistance and diabetes glucose metabolism is dysregulated and FA account for 99% of energy production. One of the major consequences of a shift in FA metabolism in cardiac tissue is an increase in reactive oxygen species (ROS) and lipotoxicity, which ultimately lead to mitochondrial dysfunction. Thyroid hormones (TH) have direct effects on cardiac function and glucose metabolism during impaired metabolic conditions suggesting that TH may improve glucose metabolism in an insulin resistant condition. None-classical TH signaling in the heart has shown to phosphorylate protein kinase B (Akt) and increase activity of phosphoinositide-3-kinase (PI3K), which are critical mediators in the insulin-stimulated glucose uptake pathway. Studies on peripheral tissues such as skeletal muscle and adipocytes have demonstrated TH treatment improved glucose intolerance in a diabetic model and increased insulin-regulated glucose transporter (GLUT4) mRNA levels. GLUT4 is a downstream target of thyroid response element (TRE), which demonstrates that THs regulate glucose via GLUT4. Elevated 3,5,3′-triiodothyronine (T3) increased glucose oxidation rate and decreased the glycolytic intermediate, fructose 6-phosphate (F6P) in cardiomyocytes, in addition to increasing mitochondrial biogenesis and pyruvate transport across the mitochondrial membrane. These findings along with a few other studies on T3 treatment in cardiac tissue suggest TH may improve glucose metabolism in an insulin resistant model and ameliorate the effects of diabetes and metabolic syndrome. This review highlights the potential benefits of exogenous TH on ameliorating metabolic dysfunction in the heart.

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“…However, 10-15% of patients with T2DM are not obese (3) and exhibit hyperglycemic events more often with higher mortality (4). The Goto-Kakizaki (GK) rat is a non-obese T2DM animal model, which shows moderate hyperglycemia, glucose intolerance, peripheral IR, chronic inflammation, reduced pancreatic b-cell number, small intestine remodeling with local inflammation, and reduced intestinal transit (5)(6)(7)(8). GK rats also present altered brain energy metabolism characterized by an impaired glutamate-glutamine cycle between neurons and astrocytes (9), cognitive dysfunction and neuroinflammation at six months of age (10), and higher levels of the Alzheimer's-related proteins p-tau and amyloid-b at 12.5 months of age (11).…”

Section: Introductionmentioning

confidence: 99%

Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats

Borges

Oliveira

Serdan

et al. 2023

Braz J Med Biol Res

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Brain glucose hypometabolism and neuroinflammation are early pathogenic manifestations in neurological disorders. Neuroinflammation may also disrupt leptin signaling, an adipokine that centrally regulates appetite and energy balance by acting on the hypothalamus and exerting neuroprotection in the hippocampus. The Goto-Kakizaki (GK) rat is a non-obese type 2 diabetes mellitus (T2DM) animal model used to investigate diabetes-associated molecular mechanisms without obesity jeopardizing effects. Wistar and GK rats received the maintenance adult rodent diet. Also, an additional control group of Wistar rats received a high-fat and high-sugar diet (HFHS) provided by free consumption of condensed milk. All diets and water were provided ad libitum for eight weeks. Brain glucose uptake was evaluated by 2-deoxy-2-[fluorine-18] fluoro-D-glucose under basal (saline administration) or stimulated (CL316,243, a selective b3-AR agonist) conditions. The animals were fasted for 10-12 h, anesthetized, and euthanized. The brain was quickly dissected, and the hippocampal area was sectioned and stored at -80°C in different tubes for protein and RNA analyses on the same animal. GK rats exhibited attenuated brain glucose uptake compared to Wistar animals and the HFHS group under basal conditions. Also, the hippocampus of GK rats displayed upregulated leptin receptor, IL-1b, and IL-6 gene expression and IL-1b and the subunit of the transcription factor NF-kB (p-p65) protein expression. No significant alterations were detected in the hippocampus of HFHS rats. Our data indicated that a genetic predisposition to T2DM has significant brain deteriorating features, including brain glucose hypometabolism, neuroinflammation, and leptin signaling disruption in the hippocampal area.

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The insulin resistance is reversed by exogenous 3,5,3′triiodothyronine in type 2 diabetic Goto–Kakizaki rats by an inflammatory-independent pathway

Cited by 6 publications

References 30 publications

Reviewing physical exercise in non-obese diabetic Goto-Kakizaki rats

Reviewing physical exercise in non-obese diabetic Goto-Kakizaki rats

Thyroid hormones and the potential for regulating glucose metabolism in cardiomyocytes during insulin resistance and T2DM

Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats

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