Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects
| Autor: | Luciano Rossetti, Pavel Shlimovich, Meyer Halberstam, Neil Cohen, Harry Shamoon |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Vanadium Compounds medicine.medical_treatment Endocrinology Diabetes and Metabolism Administration Oral Blood Pressure Fatty Acids Nonesterified chemistry.chemical_compound Lipid oxidation Reference Values Internal medicine Diabetes mellitus Diabetes Mellitus Internal Medicine Humans Hypoglycemic Agents Insulin Medicine Lipolysis Obesity Infusions Intravenous Glycogen synthase Triglycerides Glycated Hemoglobin biology business.industry Vanadyl sulfate Cholesterol HDL Cholesterol LDL Middle Aged Glucose clamp technique medicine.disease Kinetics Insulin receptor Endocrinology Diabetes Mellitus Type 2 chemistry Glucose Clamp Technique Lactates biology.protein Regression Analysis Female business Glycolysis |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0012-1797 |
| DOI: | 10.2337/diabetes.45.5.659 |
| Popis: | We compared the effects of oral vanadyl sulfate (100 mg/day) in moderately obese NIDDM and nondiabetic subjects. Three-hour euglycemic-hyperinsulinemic (insulin infusion 30 mU · m−2 · min−1) clamps were performed after 2 weeks of placebo and 3 weeks of vanadyl sulfate treatment in six nondiabetic control subjects (age 37 ± 3 years; BMI 29.5 ± 2.4 kg/m2) and seven NIDDM subjects (age 53 ± 2 years; BMI 28.7 ±1.8 kg/m2). Glucose turnover ([3-3H]glucose), glycolysis from plasma glucose, glycogen synthesis, and whole-body carbohydrate and lipid oxidation were evaluated. Decreases in fasting plasma glucose (by ∼1.7 mmol/l) and HbAlc (both P < 0.05) were observed in NIDDM subjects during treatment; plasma glucose was unchanged in control subjects. In the latter, the glucose infusion rate (GIR) required to maintain euglycemia (40.1 ± 5.7 and 38.1 ± 4.8 μmol · kg fat-free mass [FFM]−1 · min−1) and glucose disposal (Rd) (41.7 ± 5.7 and 38.9 ±4.7 μmol · kg FFM−1 · min−1) were similar during placebo and vanadyl sulfate administration, respectively. Hepatic glucose output (HGO) was completely suppressed in both studies. In contrast, in NIDDM subjects, vanadyl sulfate increased GIR ∼82% (17.3 ± 4.7 to 30.9 ± 2.7 μmol · kg FFM−1 · min−1, P < 0.05); this improvement in insulin sensitivity was due to both augmented stimulation of Rd (26.0 ±4.0 vs. 33.6 ± 2.22 μmol · kg FFM−1 · min−1, P < 0.05) and enhanced suppression of HGO (7.7 ± 3.1 vs. 1.3 ± 0.9 μmol · kg FFM−1 · min−1, P < 0.05). Increased insulin-stimulated glycogen synthesis accounted for >80% of the increased Rd with vanadyl sulfate (P < 0.005), but plasma glucose flux via glycolysis was unchanged. In NIDDM subjects, vanadyl sulfate was also associated with greater suppression of plasma free fatty acids (FFAs) (P < 0.01) and lipid oxidation (P < 0.05) during clamps. The reduction in HGO and increase in Rd were both highly correlated with the decline in plasma FFA concentrations during the clamp period (P < 0.001). In conclusion, small oral doses of vanadyl sulfate do not alter insulin sensitivity in nondiabetic subjects, but it does improve both hepatic and skeletal muscle insulin sensitivity in NIDDM subjects in part by enhancing insulin's inhibitory effect on lipolysis. These data suggest that vanadyl sulfate may improve a defect in insulin signaling specific to NIDDM. |
| Databáze: | OpenAIRE |
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