Differential effects of insulin deprivation and systemic insulin treatment on plasma protein synthesis in type 1 diabetic people

Abdul Jaleel, Katherine A. Klaus, Dawn M. Morse, Helen Karakelides, Lawrence E. Ward, Brian A. Irving, K. Sreekumaran Nair

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

It remains to be determined whether systemic insulin replacement normalizes synthesis rates of different plasma proteins and whether there are differential effects on various plasma proteins. We tested a hypothesis that insulin deprivation differentially affects individual plasma protein synthesis and that systemic insulin treatment may not normalize synthesis of all plasma proteins. We measured synthesis rates of 41 plasma proteins in seven each of type 1 diabetic (T1DM) and nondiabetic participants (ND) using [ring- 13C6]phenylalanine as a tracer. T1DM were studied while on chronic insulin treatment and during 8 h insulin deprivation. Insulin treatment normalized glucose levels, but plasma insulin levels were higher during insulin treatment than during insulin deprivation in T1DM and ND. Individual plasma proteins were purified by affinity chromatography and two-dimensional gel electrophoresis. Only 41 protein gel spots from over 300 were chosen based on their protein homogeneity. Insulin deprivation and hyperglycemia either significantly increased (n = 12) or decreased (n = 12) synthesis rates of 24 of 41 plasma proteins in T1DM compared with ND. Insulin treatment normalized synthesis rates of 13 of these 24 proteins, which were altered during insulin deprivation. However, insulin treatment significantly altered the synthesis of 14 additional proteins. In conclusion, acute insulin deprivation caused both a decrease and increase in synthesis rates of many plasma proteins with various functions. Moreover, chronic systemic insulin treatment not only did not normalize synthesis of all plasma proteins but also altered synthesis of several additional proteins that were unaltered during insulin deprivation.

Original languageEnglish (US)
Pages (from-to)E889-E897
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume297
Issue number4
DOIs
StatePublished - Oct 2009

Keywords

  • Fractional synthesis rate
  • Protein synthesis
  • Stable isotope
  • Two-dimensional gel electrophoresis
  • Type 1 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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