Counterregulation of hypoglycemia: Skeletal muscle glycogen metabolism during three hours of physiological hyperinsulinemia in humans

Neil Cohen, Luciano Rossetti, Pavel Shlimovich, Meyer Halberstam, Meizhu Hu, Harry Shamoon

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


We examined the role of skeletal muscle in counterregulation of hypoglycemia (3.4 ± 0.1 mmol/l) in 12 nondiabetic individuals (age 26 ± 1 years, body mass index 24.2 ± 0.7 kg/m2) during physiological hyperinsulinemia (280 ± 25 pmol/l) compared with euglycemia (4.8 ± 0.1 mmol/l). During hypoglycemia, hepatic glucose output (3-[3H]glucose) was greater (7.72 ± 2.72 μmol · kg-1 · min-1, P < 0.01), glucose uptake was ~49% lower (21.20 ± 3.55 μmol · kg-1 · min-1, P < 0.005), and glucose clearance was reduced (P < 0.002) compared with euglycemia. Rates of flux of plasma-derived glucosyl units through glycolysis were similar in the two experiments, while glycogen synthetic rates were significantly reduced during hypoglycemia (P < 0.01) and accounted entirely for the reduction in glucose disposal. The insulin-induced activation of skeletal muscle glycogen synthase (reflected by K(m) decline by ~50% from 0.408 ± 0.056 mmol/l and fractional velocity increase by approximately twofold from 21.8 ± 2.7%) was completely abolished in hypoglycemia. In concert, glycogen phosphorylase activity increased during hypoglycemia by ~40% (P = 0.0001). Hypoglycemia resulted in seven- to eightfold increments in plasma epinephrine (P < 0.0001) and growth hormone (P < 0.001) and 40-60% increments in plasma glucagon (P < 0.005) and cortisol (P < 0.05). We conclude that, in this model of mild hypoglycemia of moderate duration, the majority of the glucose made available during the counterregulatory process (~60-70%) is due to the limitation of glucose disposal, mostly via decreased glycogen synthetic activity in skeletal muscle.

Original languageEnglish (US)
Pages (from-to)423-430
Number of pages8
Issue number4
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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