The effect of insulin on human small intestinal mucosal protein synthesis

Background and Aims: Insulin deficiency was recently shown to stimulate splanchnic protein synthesis in vivo, whereas insulin enhances small intestinal mucosal cell proliferation in vitro. Because insulin is a postprandial hormone, it was hypothesized that it has an important role in regulating small intestinal protein synthesis in humans. Methods: Small intestinal mucosal protein synthesis was measured in C-peptide-negative patients with type I diabetes mellitus during insulin deprivation (n=6) and during insulin treatment (n=6) and in nondiabetic control subjects (n=6). Mucosal protein synthesis was measured from the increment of [¹³C]leucine enrichment in endoscopically obtained duodenal mucosa samples during a primed continuous infusion of L-[1-¹³C]leucine. Results: During insulin treatment, the rate of mucosal protein synthesis in patients with type 1 diabetes was similar (1.32% ± 0.05%/h) to that of nondiabetic controls (1.33%±0.06%/h). However, during insulin deprivation, the mucosal protein synthesis rate in patients with type I diabetes was significantly lower (1.15% ± 0.33%/h) than during either insulin treatment (P=0.01) or in nondiabetic controls (P=0.04). Conclusions: These studies show that insulin is required for the maintenance of normal rates of protein synthesis in small intestinal mucosa. Because protein synthesis is an essential component of the remodeling process of this fast turning over tissue, the decline in the synthesis rate of small intestinal mucosa during insulin deprivation may be a contributing factor in the development of gastrointestinal complications that occur in poorly controlled type 1 diabetic patients.