NMR studies of muscle glycogen synthesis in insulin-resistant offspring of parents with non-insulin-dependent diabetes mellitus immediately after glycogen-depleting exercise

Thomas B. Price, Gianluca Perseghin, Antoni Duleba, Wei Chen, Jennifer Chase, Douglas L. Rothman, Robert G. Shulman, Gerald I. Shulman

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

To examine the impact of insulin resistance on the insulin-dependent and insulin-independent portions of muscle glycogen synthesis during recovery from exercise, we studied eight young, lean, normoglycemic insulin-resistant (IR) offspring of individuals with non-insulin-dependent diabetes mellitus and eight age-weight matched control (CON) subjects after plantar flexion exercise that lowered muscle glycogen to ≃25% of resting concentration. After ≃20 min of exercise, intramuscular glucose 6-phosphate and glycogen were simultaneously monitored with 31P and 13C NMR spectroscopies. The postexercise rate of glycogen resynthesis was nonlinear. Glycogen synthesis rates during the initial insulin independent portion (0-1 hr of recovery) were similar in the two groups (IR, 15.5 ± 1.3 mM/hr and CON, 15.8 ± 1.7 mM/hr); however, over the next 4 hr, insulin-dependent glycogen synthesis was significantly reduced in the IR group [IR, 0.1 ± 0.5 mM/hr and CON, 2.9 ± 0.2 mM/hr; (P ≤ 0.001)]. After exercise there was an initial rise in glucose 6-phosphate concentrations that returned to baseline after the first hour of recovery in both groups. In summary, we found that following muscle glycogen- depleting exercise, IR offspring of parents with non-insulin-dependent diabetes mellitus had (i) normal rates of muscle glycogen synthesis during the insulin-independent phase of recovery from exercise and (ii) severely diminished rates of muscle glycogen synthesis during the subsequent recovery period (2-5 hr), which has previously been shown to be insulin-dependent in normal CON subjects. These data provide evidence that exercise and insulin stimulate muscle glycogen synthesis in humans by different mechanisms and that in the IR subjects the early response to stimulation by exercise is normal.

Original languageEnglish (US)
Pages (from-to)5329-5334
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number11
DOIs
StatePublished - May 28 1996

Keywords

  • diabetes
  • glucose 6-phosphate

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