Galanin antagonist increases insulin resistance by reducing glucose transporter 4 effect in adipocytes of rats

Guo, Lili; Shi, Mingyi; Zhang, Ling; Li, Guangzhi; Zhang, Lingxiang; Shao, Hu; Fang, Penghua; Ma, Ying‐ping; Li, Jian; Shi, Qiaojia; Sui, Yumei

doi:10.1016/j.ygcen.2011.05.011

Cited by 48 publications

(39 citation statements)

References 24 publications

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“…The obese phenotype of these mice is associated with reduced energy expenditure and insulin resistance [28] . These findings support our previous findings that endogenous galanin contributes to decreased insulin resistance and improved insulin sensitivity in rats [29][30][31] .…”

Section: Effects Of Galanin On Food Intake and Energy Expendituresupporting

confidence: 93%

“…Interestingly, galanin also promotes insulin sensitivity [28,29] . Most recently, our studies in skeletal muscle and adipocytes preliminarily verified the hypothesis that endogenous galanin notably enhances insulin sensitivity and reduces insulin resistance [30,31] . As yet it is unknown which of the three receptor subtypes is/are the most effective in enhancing insulin sensitivity.…”

Section: Resultssupporting

confidence: 67%

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Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

Fang

et al. 2011

Neurosci. Bull.

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Abstract:Galanin is a neuropeptide widely expressed in the brain. It is implicated in energy expenditure, feeding, and the regulation of body weight. Numerous studies have revealed that galanin regulates food intake via galanin receptors, 5-HT 1A receptor and adrenergic α-2 receptor. In this review, we summarize recent findings that reveal the essential role of galanin in increasing food intake as well as body weight and that identify the individual galanin receptor subtypes involved in the brain's modulation of food intake and energy expenditure, to provide a theoretical basis for further studies of different aspects of galanin action.

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Section: Effects Of Galanin On Food Intake and Energy Expendituresupporting

confidence: 93%

Section: Resultssupporting

confidence: 67%

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

Fang

et al. 2011

Neurosci. Bull.

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“…injection of 3% amobarbital sodium (50 mg/kg) individualized to each subject's body weight and subjected to hyperglycemic clamp tests, as previously described (Guo et al 2011). Insulin at a constant rate of 2 mU/kg per min was infused through a catheter into the jugular vein until the end of the test.…”

Section: Hyperinsulinemic-euglycemic Clamp and 2dg Testsmentioning

confidence: 99%

“…As a versatile regulator, this peptide may ameliorate insulin resistance via boosting glucose transporter 4 (GLUT4) translocation, leading to glucose uptake into adipose and muscle tissues (Guo et al 2011, He et al 2011. Recent studies have provided compelling clues about the relationship between galanin and insulin sensitivity.…”

Section: Introductionmentioning

confidence: 99%

“…Fourth, galaninknockout mice experienced impaired glucose disposal resulting from a reduction in insulin response and insulin-independent glucose elimination during the glucose tolerance tests (Ahrén et al 2004), while the homozygous galanin transgenic C57BL/6J mice with the obese phenotype showed reduced energy expenditure and enhanced insulin sensitivity (Poritsanos et al 2009). Finally, administration of M35, a galanin antagonist, reduced Glut4 (Slc2a4) mRNA and GLUT4 protein expression levels in the plasma membranes of myocytes and adipocytes, as well as glucose infusion rates in a hyperinsulinemic-euglycemic clamp test, which was a direct assessment of insulin sensitivity in subjects (Guo et al 2011, Liang et al 2012. These results indicate that galanin is an important hormone for elevating insulin sensitivity and glucose uptake, and that T2DM results from impairment of the functions of both galanin and insulin in the regulation of blood glucose homeostasis.…”

Section: Introductionmentioning

confidence: 99%

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Combined galanin with insulin improves insulin sensitivity of diabetic rat muscles

Yao

Liu

et al. 2014

Journal of Endocrinology

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Although administration of galanin or insulin alone may enhance insulin sensitivity and glucose transporter 4 (GLUT4) trafficking, their cooperative effect on insulin sensitivity is still unclear. In the present study, we evaluated the cooperative effect of both reagents compared with solitary treatment with galanin or insulin in type 2 diabetic rats. Galanin and/or insulin were injected singly or together into type 2 diabetic rats once a day for 15 days. The results indicated that coadministration of both reagents compared with treatment with galanin or insulin alone significantly increased glucose infusion rates in euglycemichyperinsulinemic clamp tests, 2-deoxy-[3 H]D-glucose contents, GLUT4 densities, and pAS160and protein kinase C activity levels, but reduced blood glucose and insulin levels, as well as retinol-binding protein 4 contents, and did not affect Glut4 (Slc2a4) mRNA expression levels in myocytes. The changes in the ratios of GLUT4 immunoreaction in plasma membranes to total cell membranes of myocytes were higher in the coadministrative group compared with either the insulin or the galanin group. These results indicate that cooperation of the two hormones plays a synergic role to improve GLUT4 translocation and insulin sensitivity. This finding indicates the possibility of combining galanin with insulin with the aim of obtaining better antidiabetic efficacy than that of the canonical treatment with insulin alone.

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Blocking central galanin receptors attenuates insulin sensitivity in myocytes of diabetic trained rats

Liu

Zou

et al. 2013

J of Neuroscience Research

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Galanin (Gal), a bioactive neuropeptide, is widely distributed throughout the central nervous system and has diverse modulatory effects. To understand the central effect of this training-stimulatory peptide on insulin sensitivity, its antagonist M35 was injected into the cerebral ventricle in type 2 diabetic rats. A treadmill running of the rats was used to stimulate circulating Gal secretion and central Gal mRNA expression. The results showed that M35 significantly decreased glucose infusion rates in euglycemic-hyperinsulinemic clamp tests as well as 2-deoxy-[(3) H]D-glucose uptake and peroxisome proliferator-activated receptor-α expression levels in skeletal muscles. M35 also attenuated glucose transporter 4 (GLUT4) concentration in plasma membranes and total cell membranes of myocytes, and the ratios of the GLUT4 contents in the former to the latter in M35 groups were lower than those of each diabetic control. These results imply that endogenous Gal, acting through its central receptor, may facilitate GLUT4 translocation from cytoplasm vesicles to cellular surface of myocytes to accelerate glucose uptake and to enhance insulin sensitivity in healthy and type 2 diabetic rats. Gal and its relative agents are potential targets for treatment of type 2 diabetes mellitus and its complications.

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Galanin antagonist increases insulin resistance by reducing glucose transporter 4 effect in adipocytes of rats

Cited by 48 publications

References 24 publications

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

Combined galanin with insulin improves insulin sensitivity of diabetic rat muscles

Blocking central galanin receptors attenuates insulin sensitivity in myocytes of diabetic trained rats

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