Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus

N. Cohen, M. Halberstam, P. Shlimovich, Jen Chang Chee Jen Chang, Harry Shamoon, L. Rossetti

Research output: Contribution to journalArticle

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Abstract

We examined the in vivo metabolic effects of vanadyl sulfate (VS) in non- insulin-dependent diabetes mellitus (NIDDM). Six NIDDM subjects treated with diet and/or sulfonylureas were examined at the end of three consecutive periods: placebo for 2 wk, VS (100 mg/d) for 3 wk, and placebo for 2 wk. Euglycemic hyperinsulinemic (30 mU/m2 · min) clamps and oral glucose tolerance tests were performed at the end of each study period. Glycemic control at baseline was poor (fasting plasma glucose 210±19 mg/dl; HbA(1c) 9.6±0.6%) and improved after treatment (181±14 mg/dl [P < 0.05], 8.8±0.6%, [P < 0.002]); fasting and post-glucose tolerance test plasma insulin concentrations were unchanged. After VS, the glucose infusion rate during the clamp was increased (by ~ 88%, from 1.80 to 3.38 mg/kg · min, P < 0.0001). This improvement was due to both enhanced insulin-mediated stimulation of glucose uptake (rate of glucose disposal [R(d)], +0.89 mg/kg · min) and increased inhibition of HGP (-0.74 mg/kg · min) (P < 0.0001 for both). Increased insulin-stimulated glycogen synthesis (+0.74 mg/kg · min, P < 0.0003) accounted for > 80% of the increased R(d) after VS, and the improvement in insulin sensitivity was maintained after the second placebo period. The K(m) of skeletal muscle glycogen synthase was lowered by ~ 30% after VS treatment (P < 0.05). These results indicate that 3 wk of treatment with VS improves hepatic and peripheral insulin sensitivity in insulin- resistant NIDDM humans. These effects were sustained for up to 2 wk after discontinuation of VS.

Original languageEnglish (US)
Pages (from-to)2501-2509
Number of pages9
JournalJournal of Clinical Investigation
Volume95
Issue number6
StatePublished - 1995

Fingerprint

Type 2 Diabetes Mellitus
Insulin Resistance
Liver
Placebos
Glycogen Synthase
Glucose Tolerance Test
vanadyl sulfate
Fasting
Skeletal Muscle
Therapeutics
Insulin
Diet
Glucose

Keywords

  • hepatic glucose production
  • insulin resistance
  • non- insulin-dependent diabetes mellitus
  • skeletal muscle
  • vanadium

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus. / Cohen, N.; Halberstam, M.; Shlimovich, P.; Chee Jen Chang, Jen Chang; Shamoon, Harry; Rossetti, L.

In: Journal of Clinical Investigation, Vol. 95, No. 6, 1995, p. 2501-2509.

Research output: Contribution to journalArticle

Cohen, N. ; Halberstam, M. ; Shlimovich, P. ; Chee Jen Chang, Jen Chang ; Shamoon, Harry ; Rossetti, L. / Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus. In: Journal of Clinical Investigation. 1995 ; Vol. 95, No. 6. pp. 2501-2509.
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abstract = "We examined the in vivo metabolic effects of vanadyl sulfate (VS) in non- insulin-dependent diabetes mellitus (NIDDM). Six NIDDM subjects treated with diet and/or sulfonylureas were examined at the end of three consecutive periods: placebo for 2 wk, VS (100 mg/d) for 3 wk, and placebo for 2 wk. Euglycemic hyperinsulinemic (30 mU/m2 · min) clamps and oral glucose tolerance tests were performed at the end of each study period. Glycemic control at baseline was poor (fasting plasma glucose 210±19 mg/dl; HbA(1c) 9.6±0.6{\%}) and improved after treatment (181±14 mg/dl [P < 0.05], 8.8±0.6{\%}, [P < 0.002]); fasting and post-glucose tolerance test plasma insulin concentrations were unchanged. After VS, the glucose infusion rate during the clamp was increased (by ~ 88{\%}, from 1.80 to 3.38 mg/kg · min, P < 0.0001). This improvement was due to both enhanced insulin-mediated stimulation of glucose uptake (rate of glucose disposal [R(d)], +0.89 mg/kg · min) and increased inhibition of HGP (-0.74 mg/kg · min) (P < 0.0001 for both). Increased insulin-stimulated glycogen synthesis (+0.74 mg/kg · min, P < 0.0003) accounted for > 80{\%} of the increased R(d) after VS, and the improvement in insulin sensitivity was maintained after the second placebo period. The K(m) of skeletal muscle glycogen synthase was lowered by ~ 30{\%} after VS treatment (P < 0.05). These results indicate that 3 wk of treatment with VS improves hepatic and peripheral insulin sensitivity in insulin- resistant NIDDM humans. These effects were sustained for up to 2 wk after discontinuation of VS.",
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AB - We examined the in vivo metabolic effects of vanadyl sulfate (VS) in non- insulin-dependent diabetes mellitus (NIDDM). Six NIDDM subjects treated with diet and/or sulfonylureas were examined at the end of three consecutive periods: placebo for 2 wk, VS (100 mg/d) for 3 wk, and placebo for 2 wk. Euglycemic hyperinsulinemic (30 mU/m2 · min) clamps and oral glucose tolerance tests were performed at the end of each study period. Glycemic control at baseline was poor (fasting plasma glucose 210±19 mg/dl; HbA(1c) 9.6±0.6%) and improved after treatment (181±14 mg/dl [P < 0.05], 8.8±0.6%, [P < 0.002]); fasting and post-glucose tolerance test plasma insulin concentrations were unchanged. After VS, the glucose infusion rate during the clamp was increased (by ~ 88%, from 1.80 to 3.38 mg/kg · min, P < 0.0001). This improvement was due to both enhanced insulin-mediated stimulation of glucose uptake (rate of glucose disposal [R(d)], +0.89 mg/kg · min) and increased inhibition of HGP (-0.74 mg/kg · min) (P < 0.0001 for both). Increased insulin-stimulated glycogen synthesis (+0.74 mg/kg · min, P < 0.0003) accounted for > 80% of the increased R(d) after VS, and the improvement in insulin sensitivity was maintained after the second placebo period. The K(m) of skeletal muscle glycogen synthase was lowered by ~ 30% after VS treatment (P < 0.05). These results indicate that 3 wk of treatment with VS improves hepatic and peripheral insulin sensitivity in insulin- resistant NIDDM humans. These effects were sustained for up to 2 wk after discontinuation of VS.

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