TY - JOUR
T1 - Effects of type 2 diabetes and insulin on whole-body, splanchnic, and leg protein metabolism
AU - Short, Kevin R.
AU - Irving, Brian A.
AU - Basu, Ananda
AU - Johnson, C. Michael
AU - Nair, K. Sreekumaran
AU - Basu, Rita
PY - 2012/12
Y1 - 2012/12
N2 - Context: Type 2 diabetes (T2D) is characterized by insulin resistance to glucose metabolism. Most studies suggest that protein metabolism is unaffected by T2D, but regional protein metabolism and response to multiple doses of insulin have not been examined. Objective: Our objective was to determine whether insulin regulation of splanchnic and leg protein metabolism are affected by T2D during hyperglycemia and graded insulin levels. Design and Setting: We conducted a cross-sectional study at an academic medical center. Participants: T2D and non-T2D adults were matched for age (62 yr) and body mass index (30 kg/m2). Interventions: Glucose was maintained at approximately 9 mmol/liter while insulin was infused at three progressively higher rates, achieving circulating concentrations of approximately 150, 350, and 700 pmol/liter, respectively. Main Outcome Measures: Protein kinetics were measured using labeled phenylalanine (Phe) and tyrosine (Tyr). Results: Whole-body protein breakdown and synthesis rates were higher in T2D but declined with increasing insulin in both groups. Leg Phe and Tyr appearance and disappearance and estimates of protein breakdown and synthesis, respectively, were higher in T2D but did not decline significantly with insulin, resulting in similar net balance between groups. Splanchnic response to insulin was blunted in T2D, shown by a smaller reduction in rates of disappearance and net balance of Phe and Tyr as insulin increased. Splanchnic conversion of Phe to Tyr was lower in T2D and less sensitive to insulin, whereas nonsplanchnic Phe to Tyr tended to be higher in T2D. Conclusions: T2D results in higher whole-body, splanchnic, and leg protein turnover and blunts the insulin-mediated suppression of splanchnic protein anabolism under hyperglycemic, hyperinsulinemic conditions.
AB - Context: Type 2 diabetes (T2D) is characterized by insulin resistance to glucose metabolism. Most studies suggest that protein metabolism is unaffected by T2D, but regional protein metabolism and response to multiple doses of insulin have not been examined. Objective: Our objective was to determine whether insulin regulation of splanchnic and leg protein metabolism are affected by T2D during hyperglycemia and graded insulin levels. Design and Setting: We conducted a cross-sectional study at an academic medical center. Participants: T2D and non-T2D adults were matched for age (62 yr) and body mass index (30 kg/m2). Interventions: Glucose was maintained at approximately 9 mmol/liter while insulin was infused at three progressively higher rates, achieving circulating concentrations of approximately 150, 350, and 700 pmol/liter, respectively. Main Outcome Measures: Protein kinetics were measured using labeled phenylalanine (Phe) and tyrosine (Tyr). Results: Whole-body protein breakdown and synthesis rates were higher in T2D but declined with increasing insulin in both groups. Leg Phe and Tyr appearance and disappearance and estimates of protein breakdown and synthesis, respectively, were higher in T2D but did not decline significantly with insulin, resulting in similar net balance between groups. Splanchnic response to insulin was blunted in T2D, shown by a smaller reduction in rates of disappearance and net balance of Phe and Tyr as insulin increased. Splanchnic conversion of Phe to Tyr was lower in T2D and less sensitive to insulin, whereas nonsplanchnic Phe to Tyr tended to be higher in T2D. Conclusions: T2D results in higher whole-body, splanchnic, and leg protein turnover and blunts the insulin-mediated suppression of splanchnic protein anabolism under hyperglycemic, hyperinsulinemic conditions.
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U2 - 10.1210/jc.2012-2533
DO - 10.1210/jc.2012-2533
M3 - Article
C2 - 23032060
AN - SCOPUS:84870940825
SN - 0021-972X
VL - 97
SP - 4733
EP - 4741
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 12
ER -