Role of insulin in protein metaboli

Role of insulin in protein metabolism
Insulin resistance in obesity is primary characterized by a decreased insulin-stimulated glucose disposal due to impair- ments in insulin-signalling pathway (51). However, insulin is also an important regulator of protein metabolism as this hormone, together with amino acids, is a key factor for the regulation of body protein mass (52). The main in vivo effect of insulin and amino acids on whole-body and skel- etal muscle protein metabolism is to inhibit protein break- down and to stimulate protein synthesis (53,54). In obesity, the control of protein metabolism by these factors has been shown to be modified like in other situations of insulin resistance (type 2 diabetes, ageing) (55–58). Luzi et al. observed that the regulation of protein breakdown and leucine oxidation by insulin is impaired in obese subjects receiving low dose of insulin but not in those receiving high dose of insulin (59). It is interesting to note that a similar inhibition of protein breakdown during insulin clamps is obtained with higher plasma insulin levels in obese subjects (59–61). Thus, when the difference in plasma insulin con- centration is considered in relation to the inhibitory action of this hormone on protein breakdown, significant differ- ences between the obese and the non-obese subjects for the inhibition of whole-body protein breakdown have been underlined (55). Insulin infused alone induces hyperinsuli- naemia but results in a decrease in plasma amino acid concentration to an extent that likely leads to alterations in the regulation of protein metabolism (53). Whole-body protein synthesis is normally stimulated in obese subjects during hyperaminoacidaemia with basal insulinaemia, sug- gesting that whole-body protein synthesis is still responsive to infusion of amino acid alone during obesity (59). The role of insulin, while avoiding any specific amino acid effect, has been considered by clamping plasma amino acid at their post-absorptive concentrations during a hyperinsulinaemic clamp (62). In these conditions, the blunted whole-body protein anabolic response to the action of insulin results mainly from impaired stimulation of whole-body protein synthesis in obese women. Combined infusions of insulin and amino acid failed to induce a normal inhibition of protein breakdown in non-diabetic obese subjects in com- parison with non-obese subjects (55). In this study, a lack of stimulation of muscle mitochondria protein synthesis after the insulin and amino acid clamp was also reported in the obese human subjects. It should be noted that protein metabolism in human obesity is also characterized by an elevation in plasma amino acid concentration, especially for the branched-chain amino acids (63–65). Although the increase in these amino acids has highly significant associa- tions with future development of diabetes in obese subjects
(66), the underlying mechanisms are ill-defined.

Kết quả (Việt) 1:

Vai trò của insulin trong chuyển hóa proteinInsulin resistance in obesity is primary characterized by a decreased insulin-stimulated glucose disposal due to impair- ments in insulin-signalling pathway (51). However, insulin is also an important regulator of protein metabolism as this hormone, together with amino acids, is a key factor for the regulation of body protein mass (52). The main in vivo effect of insulin and amino acids on whole-body and skel- etal muscle protein metabolism is to inhibit protein break- down and to stimulate protein synthesis (53,54). In obesity, the control of protein metabolism by these factors has been shown to be modified like in other situations of insulin resistance (type 2 diabetes, ageing) (55–58). Luzi et al. observed that the regulation of protein breakdown and leucine oxidation by insulin is impaired in obese subjects receiving low dose of insulin but not in those receiving high dose of insulin (59). It is interesting to note that a similar inhibition of protein breakdown during insulin clamps is obtained with higher plasma insulin levels in obese subjects (59–61). Thus, when the difference in plasma insulin con- centration is considered in relation to the inhibitory action of this hormone on protein breakdown, significant differ- ences between the obese and the non-obese subjects for the inhibition of whole-body protein breakdown have been underlined (55). Insulin infused alone induces hyperinsuli- naemia but results in a decrease in plasma amino acid concentration to an extent that likely leads to alterations in the regulation of protein metabolism (53). Whole-body protein synthesis is normally stimulated in obese subjects during hyperaminoacidaemia with basal insulinaemia, sug- gesting that whole-body protein synthesis is still responsive to infusion of amino acid alone during obesity (59). The role of insulin, while avoiding any specific amino acid effect, has been considered by clamping plasma amino acid at their post-absorptive concentrations during a hyperinsulinaemic clamp (62). In these conditions, the blunted whole-body protein anabolic response to the action of insulin results mainly from impaired stimulation of whole-body protein synthesis in obese women. Combined infusions of insulin and amino acid failed to induce a normal inhibition of protein breakdown in non-diabetic obese subjects in com- parison with non-obese subjects (55). In this study, a lack of stimulation of muscle mitochondria protein synthesis after the insulin and amino acid clamp was also reported in the obese human subjects. It should be noted that protein metabolism in human obesity is also characterized by an elevation in plasma amino acid concentration, especially for the branched-chain amino acids (63–65). Although the increase in these amino acids has highly significant associa- tions with future development of diabetes in obese subjects(66), the underlying mechanisms are ill-defined.