Effects of type 2 diabetes and insulin on whole-body, splanchnic, and leg protein metabolism

Kevin R. Short, Brian A. Irving, Ananda Basu, C. Michael Johnson, K Sreekumaran Nair, Rita Basu

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4733-4741
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number12
DOIs
StatePublished - Dec 2012

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Viscera
Medical problems
Metabolism
Type 2 Diabetes Mellitus
Leg
Insulin
Phenylalanine
Tyrosine
Proteins
Glucose
Hyperglycemia
Insulin Resistance
Body Mass Index
Cross-Sectional Studies
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Effects of type 2 diabetes and insulin on whole-body, splanchnic, and leg protein metabolism. / Short, Kevin R.; Irving, Brian A.; Basu, Ananda; Johnson, C. Michael; Nair, K Sreekumaran; Basu, Rita.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 12, 12.2012, p. 4733-4741.

Research output: Contribution to journalArticle

Short, Kevin R. ; Irving, Brian A. ; Basu, Ananda ; Johnson, C. Michael ; Nair, K Sreekumaran ; Basu, Rita. / Effects of type 2 diabetes and insulin on whole-body, splanchnic, and leg protein metabolism. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 12. pp. 4733-4741.
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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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