Medline Articles in the treatment of Disease
Trace Elements Arguments In The Treatment of Diabetes
Vanadium
compounds--a new class of therapeutic agents for the treatment of diabetes
mellitus].
[Article in Russian]
Beliaeva NF, Gorodetskii VK, Tochilkin
AI, Golubev MA, Semenova NV, Kovel'man IR.
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences.
Vanadium compounds as insulin mimics with promising therapeutic properties are
reviewed. The biological effects of both inorganic forms of vanadium and vanadyl
organic complexes are decried for various animal models. These effects include
hypoglycemic and insulin reserve actions, insulin sensitivity enhance,
cholesterol lowering and other manifestations. The effectiveness of vanadium
compounds in diabetes treatment is confirmed with clinical trials. The possible
mechanisms of insulin-like effects of vanadium are discussed. The various
nutritional supplements for patients with diabetes mellitus including
vanadium-contained used in Russia and abroad are also considered.
Publication Types:
· Review
· Review, tutorial
PMID: 11075417 [PubMed - indexed for MEDLINE]
Studies
of vanadyl sulfate as a glucose-lowering agent in STZ-diabetic rats.
Thompson KH, Leichter J, McNeill JH.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver,
Canada.
To study the effect of vanadium (V) intake on blood glucose lowering, tissue V
concentrations, glutathione reductase (GR) activity, and plasma trace metal
concentrations, streptozotocin(STZ)-diabetic rats were treated with vanadyl
sulfate (VS) (0.5-1.2 g/l in the drinking water) for up to 12 weeks. Kidney and
plasma V concentrations were positively correlated with V intake. Kidney GR
activities were not affected by VS treatment nor were plasma cobalt, molybdenum,
manganese or lithium concentrations. Individual V intakes were dependent upon
severity of diabetes, with more hyperglycemic rats consuming greater quantities
of VS solution. A diminished effect on glucose lowering of VS above 1 g/l was
noted.
PMID: 8280174 [PubMed - indexed for MEDLINE]
The
role of vanadium in the management of diabetes.
Brichard SM, Henquin JC.
Unite d'Endocrinologie et Metabolism, University of Louvain Faculty of Medicine,
Brussels, Belgium.
Diabetes mellitus results from an absolute or relative deficiency in insulin
secretion and a resistance of target tissues to the action of insulin, in
proportions that vary with the type of the disease. The shortage of insulin can
be corrected by administration of exogenous insulin or stimulation of pancreatic
beta-cells with sulphonylureas. However, insulin resistance remains a major
therapeutic problem. Here, Sonia Brichard and Jean-Claude Henquin review the
recent discoveries that indicate a possible role for vanadium in management of
the disease. In vitro, vanadium salts mimic most effects of insulin on the main
target tissues of the hormone, and in vivo they induce a sustained fall in blood
glucose levels in insulin-deficient diabetic rats, and improve glucose
homeostasis in obese, insulin-resistant diabetic rodents. Recent short-term
clinical trials with vanadium salts also seem promising in type II
(non-insulin-dependent) diabetic patients in whom liver and peripheral insulin
resistance was attenuated, indicating the therapeutic potential of vanadium
salts, pending demonstration of their long-term innocuity.
Publication Types:
Vanadium
compounds as insulin mimics.
Orvig C, Thompson KH, Battell M, McNeill JH.
Department of Chemistry, University of British Columbia, Vancouver, Canada.
That vanadium compounds act in an insulin-mimetic fashion both in vitro and in
vivo has been well established. Both inorganic and organic vanadium compounds
have been shown to lower plasma glucose levels, increase peripheral glucose
uptake, improve insulin sensitivity, decrease plasma lipid levels, and normalize
liver enzyme activities in a variety of animal models of both type I and type II
diabetes. Vanadium treatment of diabetic animals does not restore plasma insulin
levels but may spare pancreatic insulin. Elucidation of the mechanism(s) of
action and potentiation of vanadium's insulin-mimetic effect by appropriate
ligand binding would seem to be the highest priorities for future investigation.
Publication Types:
Increased potency of vanadium using
organic ligands.
McNeill JH, Yuen VG, Dai S, Orvig C.
Faculty of Pharmaceutical Sciences, Vancouver, B.C., Canada.
The in vivo glucose lowering effect of orally administered inorganic vanadium
compounds in diabetes was first reported in our laboratory in 1985. While both
vanadate and vanadyl forms of vanadium are orally active, they are still not
well absorbed. We have synthesized several organic vanadium compounds and one
compound, bis(maltolato)oxovanadium(lV) or BMOV, has been extensively
investigated. BMOV proved effective in lowering plasma glucose and lipids in STZ-diabetic
rats when administered in drinking water over a 25 week period. The maintenance
dose (0.18 mmol/kg/day) was approximately 50% of that required for vanadyl
sulfate (VS). Secondary complications of diabetes were prevented by BMOV and no
marked toxicity was noted. Oral gavage of STZ-diabetic rats with BMOV also
reduced blood glucose levels. The ED50 for BMOV was 0.5 mmol/kg, while for VS
the estimated ED50 was 0.9 mmol/kg. BMOV was also effective by the
intraperitoneal route in STZ-diabetic rats. The ED50 was 0.08 mmol/kg compared
to 0.22 mmol/kg for VS. Some animals treated p.o. or i.p. remained euglycemic
for up to 14 weeks. An i.v. infusion of BMOV of 0.05 mmol/kg over a 30 min
period reduced plasma glucose levels by 50% while VS was not effective.
Publication Types:
Antidiabetic
action of vanadyl in rats independent of in vivo insulin-receptor kinase
activity.
Venkatesan N, Avidan A, Davidson MB.
Department of Medicine, Cedars-Sinai Medical Center, University of California,
Los Angeles 90048.
The effects of oral vanadyl sulfate administration for 9-12 days on carbohydrate
and lipid metabolism in the basal state and on glucose dynamics during
submaximal hyperinsulinemic clamps were investigated in nondiabetic and
streptozocin-induced diabetic rats. Decreases in growth rate and water and food
consumption were the only significant alterations noted in control animals
receiving vanadyl. Administration of vanadyl to diabetic rats resulted in weight
loss; a significant decrease in plasma glucose, triglyceride, and cholesterol
levels; and decreases in food and water intake, without a concomitant change in
plasma insulin concentrations. Vanadyl treatment did not modify either
peripheral glucose utilization or hepatic glucose production in control rats
during submaximal insulin clamps. In contrast, vanadyl therapy increased
insulin-induced glucose utilization significantly and had a small but
nonsignificant effect on insulin-mediated suppression of glucose production in
diabetic rats. The tyrosine kinase activity of liver- and muscle-derived insulin
receptors from diabetic rats that underwent clamp study, which reflected the in
vivo phosphorylation state of insulin receptor, was not altered by vanadyl
treatment. In conclusion, these results show that augmentation of peripheral
glucose utilization is the major determinant of the antidiabetic action of
vanadyl and support the notion that the action of vanadyl is independent of
insulin-receptor kinase activity.
PMID: 1849104 [PubMed - indexed for MEDLINE]
Studies of vanadyl sulfate as a
glucose-lowering agent in STZ-diabetic rats.
Thompson KH, Leichter J, McNeill JH.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver,
Canada.
To study the effect of vanadium (V) intake on blood glucose lowering, tissue V
concentrations, glutathione reductase (GR) activity, and plasma trace metal
concentrations, streptozotocin(STZ)-diabetic rats were treated with vanadyl
sulfate (VS) (0.5-1.2 g/l in the drinking water) for up to 12 weeks. Kidney and
plasma V concentrations were positively correlated with V intake. Kidney GR
activities were not affected by VS treatment nor were plasma cobalt, molybdenum,
manganese or lithium concentrations. Individual V intakes were dependent upon
severity of diabetes, with more hyperglycemic rats consuming greater quantities
of VS solution. A diminished effect on glucose lowering of VS above 1 g/l was
noted.
PMID: 8280174 [PubMed - indexed for MEDLINE]
Increased
potency of vanadium using organic ligands.
McNeill JH, Yuen VG, Dai S, Orvig C.
Faculty of Pharmaceutical Sciences, Vancouver, B.C., Canada.
The in vivo glucose lowering effect of orally administered inorganic vanadium
compounds in diabetes was first reported in our laboratory in 1985. While both
vanadate and vanadyl forms of vanadium are orally active, they are still not
well absorbed. We have synthesized several organic vanadium compounds and one
compound, bis(maltolato)oxovanadium(lV) or BMOV, has been extensively
investigated. BMOV proved effective in lowering plasma glucose and lipids in STZ-diabetic
rats when administered in drinking water over a 25 week period. The maintenance
dose (0.18 mmol/kg/day) was approximately 50% of that required for vanadyl
sulfate (VS). Secondary complications of diabetes were prevented by BMOV and no
marked toxicity was noted. Oral gavage of STZ-diabetic rats with BMOV also
reduced blood glucose levels. The ED50 for BMOV was 0.5 mmol/kg, while for VS
the estimated ED50 was 0.9 mmol/kg. BMOV was also effective by the
intraperitoneal route in STZ-diabetic rats. The ED50 was 0.08 mmol/kg compared
to 0.22 mmol/kg for VS. Some animals treated p.o. or i.p. remained euglycemic
for up to 14 weeks. An i.v. infusion of BMOV of 0.05 mmol/kg over a 30 min
period reduced plasma glucose levels by 50% while VS was not effective.
Publication Types:
Oral
vanadyl sulfate in treatment of diabetes mellitus in rats.
Ramanadham S, Mongold JJ, Brownsey RW, Cros GH, McNeill JH.
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences,
University of British Columbia, Vancouver, Canada.
Recent reports have suggested that vanadium in the form of vanadyl (+IV)
possesses insulin-like activity. Therefore, in the present study we examined the
effects of administering oral vanadyl to diabetic animals. Wistar rats made
diabetic with streptozotocin and age-matched controls were maintained for 10 wk
in the absence and presence of vanadyl sulfate trihydrate in the drinking water.
In the presence of vanadyl, decreases in rate of growth and circulating levels
of insulin were the only significant alterations recorded in control animals. In
contrast, diabetic animals treated with vanadyl, despite having lower body
weights and insulin levels, had normal plasma concentrations of glucose, lipid,
creatinine, and thyroid hormone. In addition, abnormalities in isolated working
heart function and glycerol output from adipose tissue of diabetic animals were
also corrected after vanadyl treatment. These results suggest that vanadium when
used in the vanadyl form is effective in diminishing the diabetic state in the
rat by substituting for and replacing insulin or possibly by enhancing the
effects of endogenous insulin.
PMID: 2675634 [PubMed - indexed for MEDLINE]
Magnesium
and ascorbic acid supplementation in diabetes mellitus.
Eriksson J, Kohvakka A.
Malmi Municipal Hospital, Helsinki, Finland.
The effect of magnesium (Mg) and ascorbic acid (AA) supplementation on metabolic
control was assessed in 56 outpatient diabetics. A 90-day run-in period was
followed by two 90-day treatment periods, during which Mg (600 mg/day) and AA (2
g/day) were administered in a randomized double-blind cross-over fashion. A
decrease in systolic and diastolic blood pressure (132 +/- 3 vs. 138 +/- 4 and
77 +/- 2 vs. 82 +/- 2 mm Hg; p < 0.05) was observed in insulin-dependent
diabetes mellitus subjects during Mg supplementation. No beneficial effect of Mg
supplementation was observed on glycemic control, lipids or blood pressure in
non-insulin-dependent diabetes mellitus (NIDDM) subjects. AA supplementation
improved glycemic control among NIDDM subjects and both fasting blood glucose
(9.1 +/- 0.5 vs. 10.1 +/- 0.6 mmol/l; p < 0.05) and HbA1c (8.5 +/- 0.3 vs.
9.3 +/- 0.3%; p < 0.05) improved. Beneficial effects of AA supplementation on
cholesterol (5.9 +/- 0.2 vs. 6.2 +/- 0.2 mmol/l; p < 0.05) and triglycerides
(2.2 +/- 0.2 vs. 2.5 +/- 0.2; p < 0.05) were also observed in NIDDM subjects.
The results suggest that high-dose AA supplementation may have a beneficial
effect in NIDDM subjects on both glycemic control and blood lipids.
Publication Types:
· Clinical trial
· Randomized controlled trial
PMID: 8546437 [PubMed - indexed for MEDLINE]
|
N Engl J Med 1997 Sep 4;337(10):670-6 |
Comment in:
· ACP J Club. 1998 Mar-Apr;128(2):47
· N Engl J Med. 1997 Sep 4;337(10):701-2
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