In an attempt to elucidate the effect of vanadium compounds on the gene expression of neuropeptide Y (NPY), vanadyl sulfate (VOSO4) was orally administrated at the dose of 1 mg/kg body weight into streptozotocin-induced diabetic rats (STZ-diabetic rats) three times daily for 1 week. We found a marked lowering of plasma glucose with a significant decrease of food and water intake in these STZ-diabetic rats treated with VOSO4, although the weight gain was unaffected. The increase of hypothalamic NPY, both the mRNA level and peptide concentration, in STZ-diabetic rats was also reduced by this oral treatment of VOSO4. However, similar treatment of VOSO4 in normal rats failed to modify the feeding behavior and hypothalamic NPY gene expression. These data suggest that decrease of hypothalamic NPY gene expression by VOSO4 is related to the recovery of hyperphagia in diabetic rats lacking insulin.
Key words:
Vanadyl Sulfate - Neuropeptide Y Gene Expression - Diabetic Rat
References
-
1
Chavez M, Seeley RJ, Havel P J, Friedman M I, Matson C A, Woods S C, Schwartz M W.
Effect of a high-fat diet on food intake and hypothalamic neuropeptide gene expression in streptozotocin diabetes.
J Clin Invest.
1998;
102
340-346
-
2
Marks J L, Waite K, Li M.
Effects of streptozotocin-induced diabetes mellitus and insulin treatment on neuropeptide Y mRNA in the rat hypothalamus.
Diabetologia.
1993;
36
497-502
-
3
Williams G, Gill J S, Lee Y C, Cardoso H M, Okpere B E, Bloom S R.
Increased neuropeptide Y concentrations in specific hypothalamic regions of streptozotocin-induced diabetic rats.
Diabetes.
1989;
38
321-327
-
4
Bai F L, Yamano M, Shiotani Y, Emson P C, Smith A D, Powell J F, Fohyama M.
An arcuate-paraventricular and dorsomedial hypothalamic neuropeptide Y-containing system which lacks noradrenaline in the rat.
Brain Res.
1985;
33
172-175
-
5
Frankish H M, McCarthy H D, Dryden S, Kilpatrick A, Williams G.
Neuropeptide Y receptor numbers are reduced in the hypothalamus of streptozotocin-diabetic and food-deprived rats: further evidence of increased activity of hypothalamic NPY-containing pathways.
Peptides.
1993;
14
941-948
-
6
McKibbin P E, McCarthy H D, Shaw P, Williams G.
Insulin deficiency is a specific stimulus to hypothalamic neuropeptide Y: a comparison of the effects of insulin replacement and food restriction in streptozotocin-diabetic rats.
Peptides.
1992;
13
721-727
-
7
Malabu U H, McCarthy H D, McKibbin P E, Williams G.
Peripheral insulin administration attenuates the increase in neuropeptide Y concentrations in the hypothalamic arcuate nucleus of fasted rats.
Peptides.
1992;
13
1097-1102
-
8
Hirsova D, Koldovsky O.
On the question of the absorption of insulin from the gastrointestinal tract during postnatal development.
Physiol Bohemoslov.
1969;
18
281-284
-
9
Ramasarma T, Crane F L.
Dose vanadium play a role in cellular regulation?.
Curr Topic Cell Regul.
1991;
20
247-301
-
10
Cantley L C Jr, Resh M D, Guidotti G.
Vanadate inhibits the red cell (Na+, K+) ATPase from the cytoplasmic side.
Nature.
1978;
272
552-554
-
11
Degani H, Gochin M, Karlish S J, Shechter Y.
Electron paramagnetic resonance studies and insulin-like effects of vanadium in rat adipocytes.
Biochemistry.
1981;
20
5795-5799
-
12
Pederson R A, Ramanadham S, Buchan A M, McNeill J H.
Long-term effects of vanadyl treatment of streptozotocin-induced diabetes in rats.
Diabetes.
1989;
38
1390-1395
-
13
Malabu U H, Dryden S, McCarthy H D, Kilpatrick A, Williams G.
Effects of chronic vanadate administration in the STZ-induced diabetic rats. The antihyperglycemic action of vanadate is attributable entirely to its suppression of feeding.
Diabetes.
1994;
43
9-15
-
14 Hudson F TG. Toxicology and biological significance. New York; Elsevier press 1964
-
15
Domingo J L, Gomez M, Sanchez D J, Llobet J M, Keen C L.
Toxicology of vanadium compounds in diabetic rats: the action of chelating agents on vanadium accumulation.
Mol Cell Biochem.
1995;
153
233-240
-
16
Shechter Y.
Insulin-mimetic effects of vanadate. Possible implications for future treatment of diabetes.
Diabetes.
1990;
39
1-5
-
17
Niu C S, Chang T W, Cheng J T.
Changes of neuropeptide Y messenger RNA and peptide by drugs influencing endogenous norepinephrine content in cerebrocortex of the rat.
J Neurochem.
1996;
66
2100-2104
-
18
Liu I M, Hsu F L, Chen C F, Cheng J T.
Antihyperglycemic action of isoferulic acid in streptozotocin-induced diabetic rats.
Br J Pharmacol.
2000;
29
631-636
-
19
Matsushita R, Sakurai H.
Mechanism on insulin-like action of vanadyl sulfate: studies on interaction between rat adipocytes and vanadium compounds.
Biol Pharm Bull.
1995;
18
719-725
-
20
Reuland D J, Cao Z X, Rosenhein L, Poehlein S, McCoy L, Turner J, Durham T, Ganguli S.
The cellular uptake kinetics and acute biological effects of various oxovanadium species: a comparative study.
Horm Metab Res.
1998;
30
29-33
-
21
Jallat-Marfaing P, Penicaud L.
Effect of vanadium on regional brain glucose utilization in rats.
Physiol Behav.
1993;
54
407-409
-
22
Morely J E.
Neuropeptide regulation of appetite and weight.
Endocr Rev.
1987;
8
256-287
-
23
Nakai M, Watanabe H, Fujiwara C, Kakegawa H, Satoh T, Takada J, Sahu A.
Leptin decreases food intake induced by melanin-concentrating hormone (MCH), galanin (GAL) and neuropeptide Y (NPY) in the rat.
Endocrinology.
1998;
139
4739-4742
-
24
Schwartz M W, Baskin D G, Bukowski T R, Kuijper J L, Fuster D, Lasser G, Prunkard D E, Porte D Jr, Woods S C, Seeley R J, Weigle D S.
Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice.
Diabetes.
1996;
45
531-535
-
25
Havel P J, UriU-Hare J Y, Liu T, Stanhope K L, Stern J S, Keen C L, Ahren B.
Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin.
Am J Physiol.
1998;
274
R1482-R1491
-
26
McKibbin P E, Cotton S J, McCarthy H D, Williams G.
The effect of dexamethasone on neuropeptide Y concentrations in specific hypothalamic regions.
Life Sci.
1992;
51
1301-1307
-
27
Yuen V G, Orvig C, McNeill J H.
Effects of bis(maltolato)oxovanadium(IV) are distinct from food restriction in STZ-diabetic rats.
Am J Physiol.
1997;
272
E30-E35
Prof. J. T. Cheng
Department of Pharmacology,
College of Medicine, National Cheng Kung University
Tainan City, Taiwan
70101, R.O.C.
Phone: Phone:+ 886 (6) 237-2706
Fax: Fax:+ 886 (6) 238-6548
Email: E-mail:jtcheng@mail.ncku.edu.tw
