Postabsorptive muscle protein metabolism in type 1 diabetic patients after pancreas transplantation.
Insulin was shown to induce protein anabolism in vivo mainly by inhibiting proteolysis. Heterotopic pancreas transplantation in type 1 diabetes mellitus is characterized by peripheral hyperinsulinemia due to systemic rather than portal insulin delivery. Therefore, we studied the postabsorptive muscle protein metabolism in type 1 diabetic patients with or without pancreas transplantation. The forearm balance technique was performed in 9 type 1 diabetic patients on exogenous insulin treatment, in 4 type 1 diabetic patients following successful pancreas transplantation and in 6 healthy volunteers. Labelled leucine and phenylalanine were infused to quantify whole-body and muscle protein synthesis, respectively. In the postabsorptive state, whole-body protein synthesis (leucine kinetics) was similar in pancreas-transplanted patients and controls. In contrast, muscle protein synthesis tended to be less negative in pancreas-transplanted patients with respect to type 1 diabetic patients and healthy volunteers. The present data suggest that recipients with peripheral insulin delivery and chronic hyperinsulinemia are characterized by a preferential stimulation of protein synthesis in muscle rather than in the splanchnic district. When insulin was infused acutely, while maintaining euglycemia, the whole-body and muscle protein synthesis rates were approximately halved in type 1 diabetic patients with and without pancreas transplantation. We conclude that pancreas transplantation is able to normalize basal and insulin-stimulated protein metabolism. Chronic hyperinsulinemia counteract steroid-induced protein degradation by means of a mild, but persistent stimulation of muscle protein synthesis.
Luzi
L
L
Departments of Medicine and Surgery, San Raffaele Scientific Institute, University of Milan, Milan, Italy.
Piceni Sereni
L
L
Spessot
M
M
Dodesini
R
R
Pastore
M R
MR
Bianchi
E
E
Terruzzi
I
I
Secchi
A
A
Cristallo
M
M
Pozza
G
G
Di Carlo
V
V
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery*; D002149:Energy Intake; D005542:Forearm; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D007930:Leucine / Q000097:blood / Q000378:metabolism; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D016035:Pancreas Transplantation / Q000502:physiology*; D010649:Phenylalanine / Q000097:blood / Q000378:metabolism; D011241:Prednisone / Q000627:therapeutic use; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D012016:Reference Values; D012039:Regional Blood Flow
D001786:Blood Glucose; D002096:C-Peptide; D016572:Cyclosporine; D006442:Glycated Hemoglobin; D007166:Immunosuppressive Agents; D007328:Insulin; D007930:Leucine; D009124:Muscle Proteins; D010649:Phenylalanine; D011241:Prednisone; D011506:Proteins