Effect of poor diabetic control and obesity on whole body protein metabolism in man

Abstract

We have investigated whole body protein turnover in the fasted state in five normal men, five male Type 1 diabetic patients off insulin therapy, and five obese women, using IV 13C-leucine as a tracer. In diabetic patients, there was, as expected, a greater net loss of protein in the fasted state than in normal subjects. However, contrary to animal and studies in vitro, our diabetic patients in the fasted state showed a greater rate of protein synthesis than normal subjects (p less than 0.01). The increased net loss of protein in diabetic patients compared with normal subjects arose because, in the diabetic patients, protein breakdown was increased even more than protein synthesis under the conditions of this study. Plasma leucine concentration was higher in diabetic and in insulin-insensitive obese patients than in normal subjects (p less than 0.01), and higher in diabetic than in obese patients (p less than 0.05). The rate of protein synthesis per kg lean body mass was also higher in diabetic patients than in obese or normal subjects (p less than 0.01), and higher in obese than normal subjects (p less than 0.05). We conclude that, in human subjects, whole body leucine and protein metabolism are very sensitive to the action of insulin.

Renal amino acid, fat and glucose metabolism in type 1 diabetic and non-diabetic humans: effects of acute insulin withdrawal

“…In untreated type 1 diabetes prolonged lack of insulin leads to cachexia, excessive urinary nitrogen loss and decreased lean body mass, all of which revert to normal upon insulin therapy [25][26][27]. In accordance with previous studies [2,3] we found that insulin deprivation increases whole-body protein breakdown, as evidenced by increased flux rates of phenylalanine, tyrosine and leucine of around 20%. This effect is to some extent offset by a concomitant increase in protein synthesis, which could relate to increased levels of circulating amino acids.…”

“…Insulin deprivation increases production of glucose and lipid intermediates [1], accelerates proteolysis [2,3] and alters substrate disposal. This results in high plasma concentration levels of NEFA, ketone bodies and increased circulating concentrations of most amino acids [1][2][3].…”

“…Insulin deprivation increases production of glucose and lipid intermediates [1], accelerates proteolysis [2,3] and alters substrate disposal. This results in high plasma concentration levels of NEFA, ketone bodies and increased circulating concentrations of most amino acids [1][2][3]. Until recently it was assumed that the primary tissues participating in these events were liver (increased glucose production and ketogenesis), adipose tissue (increased lipolysis) and muscle (increased proteolysis) [1][2][3].…”

“…This results in high plasma concentration levels of NEFA, ketone bodies and increased circulating concentrations of most amino acids [1][2][3]. Until recently it was assumed that the primary tissues participating in these events were liver (increased glucose production and ketogenesis), adipose tissue (increased lipolysis) and muscle (increased proteolysis) [1][2][3]. Several reports have suggested that in addition the kidney may be an important component in the regulation of intermediary metabolism, in particular glucose metabolism [4].…”

“…It is well established that insulin deprivation leads to high protein turnover with disproportionately increased protein degradation [2,3]. Analysis of regional protein turnover by means of catheterisation has revealed that the increase in protein synthesis almost exclusively occurs in the splanchnic bed, whereas the excessive protein breakdown is most pronounced in muscle [3].…”