Skeletal muscle proteolysis is reduced in noninsulin-dependent diabetes mellitus and is unaltered by euglycemic hyperinsulinemia or intensive insulin therapy

Scott Denne, G. Brechtel, A. Johnson, E. A. Liechty, A. D. Baron

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

To assess how noninsulin-dependent diabetes mellitus (NIDDM) and diabetes control may alter whole body and skeletal muscle proteolysis, we measured the rate of appearance (Ra) of phenylalanine (reflecting proteolysis) in the whole body and across the leg (reflecting skeletal muscle), using a constant tracer infusion of [2H5] phenylalanine in the basal state and during high- dose euglycemic hyperinsulinemia in 6 NIDDM and 10 control subjects. Studies were performed in NIDDM subjects 2 weeks after complete withdrawal of antidiabetic treatment and again after intensive insulin therapy. After intensive treatment, significant reductions were measured in hemoglobin A1C, fasting glucose concentrations, and basal hepatic glucose output. In contrast, there was no change after therapy in basal whole body or leg phenylalanine Ra. Compared with that of controls, whole body phenylalanine Ra was significantly higher and leg phenylalanine Ra significantly lower in NIDDM subjects. During euglycemic hyperinsulinemia, whole body phenylalanine Ra was significantly suppressed (~15%) below basal values before and after therapy in NIDDM subjects and similarly suppressed in control subjects. However, in NIDDM subjects, euglycemic hyperinsulinemia did not reduce leg phenylalanine Ra below basal values either before or after therapy, whereas hyperinsulinemia resulted in a 42% suppression of leg phenylalanine Ra in controls. We conclude that 1) the clear improvement in glucose metabolism produced by intensive insulin therapy in NIDDM is not accompanied by changes in whole body or skeletal muscle proteolysis; 2) skeletal muscle proteolysis is reduced even though whole body proteolysis is increased in NIDDM subjects compared with controls; and 3) although a high-dose systemic infusion of insulin significantly reduces whole body proteolysis in both NIDDM and control subjects, skeletal muscle proteolysis is suppressed only in controls. We speculate that in NIDDM, high basal insulin concentrations (~200 pmol/L, unaltered by therapy) maximally suppress skeletal muscle proteolysis, and therefore higher insulin concentrations produce no additional suppression in skeletal muscle.

Original languageEnglish
Pages (from-to)2371-2377
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume80
Issue number8
StatePublished - 1995

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Proteolysis
Hyperinsulinism
Medical problems
Type 2 Diabetes Mellitus
Phenylalanine
Muscle
Skeletal Muscle
Insulin
Leg
Therapeutics
Glucose
Hypoglycemic Agents
Fasting
Hemoglobins
Metabolism

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Skeletal muscle proteolysis is reduced in noninsulin-dependent diabetes mellitus and is unaltered by euglycemic hyperinsulinemia or intensive insulin therapy. / Denne, Scott; Brechtel, G.; Johnson, A.; Liechty, E. A.; Baron, A. D.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 80, No. 8, 1995, p. 2371-2377.

Research output: Contribution to journalArticle

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abstract = "To assess how noninsulin-dependent diabetes mellitus (NIDDM) and diabetes control may alter whole body and skeletal muscle proteolysis, we measured the rate of appearance (Ra) of phenylalanine (reflecting proteolysis) in the whole body and across the leg (reflecting skeletal muscle), using a constant tracer infusion of [2H5] phenylalanine in the basal state and during high- dose euglycemic hyperinsulinemia in 6 NIDDM and 10 control subjects. Studies were performed in NIDDM subjects 2 weeks after complete withdrawal of antidiabetic treatment and again after intensive insulin therapy. After intensive treatment, significant reductions were measured in hemoglobin A1C, fasting glucose concentrations, and basal hepatic glucose output. In contrast, there was no change after therapy in basal whole body or leg phenylalanine Ra. Compared with that of controls, whole body phenylalanine Ra was significantly higher and leg phenylalanine Ra significantly lower in NIDDM subjects. During euglycemic hyperinsulinemia, whole body phenylalanine Ra was significantly suppressed (~15{\%}) below basal values before and after therapy in NIDDM subjects and similarly suppressed in control subjects. However, in NIDDM subjects, euglycemic hyperinsulinemia did not reduce leg phenylalanine Ra below basal values either before or after therapy, whereas hyperinsulinemia resulted in a 42{\%} suppression of leg phenylalanine Ra in controls. We conclude that 1) the clear improvement in glucose metabolism produced by intensive insulin therapy in NIDDM is not accompanied by changes in whole body or skeletal muscle proteolysis; 2) skeletal muscle proteolysis is reduced even though whole body proteolysis is increased in NIDDM subjects compared with controls; and 3) although a high-dose systemic infusion of insulin significantly reduces whole body proteolysis in both NIDDM and control subjects, skeletal muscle proteolysis is suppressed only in controls. We speculate that in NIDDM, high basal insulin concentrations (~200 pmol/L, unaltered by therapy) maximally suppress skeletal muscle proteolysis, and therefore higher insulin concentrations produce no additional suppression in skeletal muscle.",
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