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Use of cardiotrophin- 1 for the treatment of metabolic diseases

A technology for cardiotrophin and metabolic diseases, applied in the field of cardiotrophin-1 for treating metabolic diseases

Inactive Publication Date: 2012-01-11
PROYECTO DE BIOMEDICINA CIMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the use of said cytokines as therapeutic agents is limited by the low expression of CNTFRα receptors in adipose and muscle tissue, high numbers in the CNS, production of anti-CNTF antibodies

Method used

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  • Use of cardiotrophin- 1 for the treatment of metabolic diseases
  • Use of cardiotrophin- 1 for the treatment of metabolic diseases
  • Use of cardiotrophin- 1 for the treatment of metabolic diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] Effect of CT-1 on body weight

[0113] Obese mice were obtained by ingesting a high fat diet (HFD, 60% fat) for 3 months. Intravenous injection of rCT-1 (0.2 mg / kg / day) for 6 consecutive days resulted in a decrease in body weight ( figure 1 ). The doses used in this study did not induce febrile reactions (rectal temperature was measured daily during treatment).

[0114] like figure 1 The obese mice fed with the indicated HFD and injected with the aforementioned 0.2 mg / kg / day dose of rCT-1 for 6 consecutive days observed a decrease in body weight, which was due to the appetite-suppressing effect of this cytokine ( figure 2 ). The graph shows the calorie intake over six days of treatment for the rCT-1 treated group and the corresponding control group treated intravenously with physiological serum.

[0115] Similarly, continuous 6-day intravenous injection of rCT-1 (0.2 mg / kg / day) also caused weight loss ( image 3 ). The doses administered in this experiment did n...

Embodiment 2

[0118] CT-1 blood sugar lowering effect

[0119] To determine whether acute intravenous injection of a single dose of rCT-1 (10 μg) into C57BL / 6 mice (3 months old) would reduce baseline blood glucose levels, blood glucose levels were measured after 1 hr treatment with rCT-1 and saline serum. like Figure 5 As shown in A, rCT-1 significantly lowered the blood glucose level. Mechanisms of blood glucose lowering are not due to elevated blood insulin levels (eg, Figure 5 B), because the insulin levels of animals treated with rCT-1 and saline serum were not significantly different. Results are expressed as mean ± SE. n=5 animals per group, *p Figure 5 C shows a representative Western).

[0120] Acute administration of a single dose (10 μg) of rCT-1 suppressed blood glucose elevation after a high glucose diet. In order to study the effect of rCT-1 on postprandial blood glucose, mice (C57BL / 6, 3 months old) were used to carry out the following experiments: the mice were given ...

Embodiment 3

[0131] Different effects of CT-1 and CNTF

[0132] Figure 16 Shown are the results of experiments performed in rat adipocyte primary cultures to determine the ability of rCT-1 and CNTF to regulate adipocyte leptin secretion. Figure 16 A shows that rCT-1 treatment (72 hours) is able to suppress both basal and insulin-stimulated secretion of leptin (1.6 nM). However, these effects were not observed at the same concentration of CNTF ( Figure 16 B).

[0133] Figure 17Shown are the results of experiments performed in primary cultures of rat adipocytes to determine the ability of CT-1 and CNTF to regulate lipolysis in the presence or absence of insulin. The figure shows that CT-1 is able to induce the release of glycerol (measured by lipolysis) and inhibits the antilipolytic activity of insulin, whereas CNTF is not. These data suggest that CT-1 is able to mobilize fat and, as previously shown, increase beta oxidation in muscle, suggesting that this cytokine can reduce fat a...

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Abstract

The invention is related to the use of cardiotrophin-1 (CT-I) for the treatment of obesity and associated disorders: hyperglycaemias, insulin resistance, development of type 2 diabetes and dyslipemias and given its anorexigenic role, fat oxidation stimulant, hypoglycaemic, sensitizing agent of the action of insulin on a skeletal muscle level and inhibitor of the intestinal transport of glucose by enterocytes.

Description

technical field [0001] The present invention relates to the use of cardiotrophin-1 for treating obesity and other related diseases, such as: hyperglycemia, insulin resistance, type 2 diabetes and dyslipidemia, etc. Cardiotrophin has the function of suppressing appetite and can act as a Stimulator, hypoglycemic sensitizer of insulin action at the level of skeletal muscle and inhibitor of intestinal transfer of glucose by enterocytes. technical background [0002] Obesity is a serious public health problem that has reached epidemic proportions in many developed countries (Bellange and Bray, 2005, J The State Med Soc; 157: S42-49; quiz 49). Increased food intake, unhealthy eating habits and sedentary lifestyles have undoubtedly contributed to the surge in obesity in our developed countries (Stein and Colditz et al., 2004, J. Clin. Endocrinol. Metab. 89: 2522-5). Numerous studies have shown that the worrying increase in the prevalence of obesity and other metabolic diseases is...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/19A61P3/10A61P3/00
CPCA61K38/204A61K38/28A61P3/00A61P3/04A61P3/06A61P3/10
Inventor 赫苏斯·玛丽亚·普列托·巴尔图埃纳马蒂尔德·布斯托斯·德·阿凡霍玛丽亚·赫苏斯·莫雷尼奥·阿里阿加
Owner PROYECTO DE BIOMEDICINA CIMA
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