Metabolic effects of sodium metavanadate in humans with insulin-dependent and noninsulin-dependent diabetes mellitus in vivo and in vitro studies.
To investigate the efficacy and mechanism of action of sodium metavanadate as an oral hypoglycemic agent, five insulin-dependent diabetes mellitus (IDDM) and five noninsulin-dependent diabetes mellitus (NIDDM) patients were studied before and after 2 weeks of oral sodium metavanadate (NaVO3; 125 mg/day). Glucose metabolism measured during a two-step euglycemic insulin clamp was not significantly increased by vanadate therapy in patients with IDDM, but was improved by 29% during the low dose (0.5 mU/kg.min) insulin infusion and 39% during the high dose (1.0 mU/kg.min) in patients with NIDDM. The changes in glucose metabolism were largely accounted for by an increase in nonoxidative glucose disposal, as measured by indirect calorimetry. Basal hepatic glucose production and suppression of hepatic glucose production by insulin were unchanged by vanadate therapy. There was a significant decrease in insulin requirements in the patients with IDDM (39.1 +/- 6.6 to 33.8 +/- 4.7 U/day; P < 0.05). Cholesterol levels significantly decreased in both IDDM (4.53 +/- 0.16 vs. 4.27 +/- 0.22 mmol/L; P = 0.06) and NIDDM (6.92 +/- 0.75 vs. 5.28 +/- 0.46 mmol/L; P < 0.05). After NaVO3 therapy, there was a 1.7- to 3.9-fold increase in basal mitogen-activated protein and S6 kinase activities in mononuclear cells from patients with IDDM and NIDDM that mimicked the effect of insulin stimulation in controls. The most common adverse effect of oral NaVO3 was mild gastrointestinal intolerance. These data suggest that vanadate or related agents may have a potential role as adjunctive therapy in patients with diabetes mellitus.
Goldfine
A B
AB
Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
Simonson
D C
DC
Folli
F
F
Patti
M E
ME
Kahn
C R
CR
D000328:Adult; D000368:Aged; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1; D017346:Protein Serine-Threonine Kinases / Q000097:blood; D011505:Protein-Tyrosine Kinases / Q000097:blood; D019893:Ribosomal Protein S6 Kinases; D014638:Vanadates / Q000009:adverse effects / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D007328:Insulin; D014638:Vanadates; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1